|
|
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Corneal Atlas Inflammation and infection often—but not always—go hand in hand. Part Two of our series reviews the common causes and current treatments for corneal inflammatory disorders.
by Joseph Sowka, O.D. and Alan Kabat, O.D., Contributing Editors As a rule, where there's corneal infection, corneal inflammation follows. Most often we prefer to address the infectious agent, then consider the inflammatory
response secondarily, if at all.
Interstitial Keratitis Today, the most common identifiable cause of active cases of IK is herpes simplex virus (HSV).1 While HSV and herpes zoster virus (HZV) can cause IK, they both also have other immune-mediated inflammatory reactions within the corneal stroma. IK is also idiopathic in many cases.1 Active IK manifests as white patches representing stromal inflammation and infiltration, edema, and often stromal neovascularization. The latter need not be present to make this diagnosis, as was once thought. Stromal vascularization will typically begin in the acute phase and progress throughout the course of the disease. Stromal infiltration and edema may be either diffuse, sectorial or multifocal. Anterior uveitis, keratic precipitates and endothelial folds are common (see table 2). Typically, the overlying epithelium is intact. Occasionally, there will be epithelial disruption, but it will be much smaller in area than the underlying stromal inflammation.1,11 IK is an immunologically mediated inflammation, with no active microbial cells within the stroma. Rather, microbial antigens initiate T-lymphocyte-mediated destruction of the stroma.11 However, the differentiation of infectious and immunologic changes is not always clear. Corneal stromal thinning may occur as a result of the chronic inflammation, but it is not a distinctive feature of IK, especially during the active phase.11
Patients with active IK will experience pain, photophobia, lacrimation and blepharospasm. IK may be either unilateral or bilateral; it's generally self-limiting and
will spontaneously subside over a period of weeks to months.11,12 You should treat IK, however, and not only to hasten the resolution of the disease. Untreated, IK can
lead to stromal scarring and vascularization with potentially severe vision loss.12 An immunologic condition, IK does respond to topical corticosteroids. Moderately
aggressive use of topical corticosteroids is indicated in most cases, except for IK caused by viral (herpetic) disease. In cases of herpetic IK, use lower doses of
corticosteroids and prophylactic antiviral medications to prevent epithelial infection. Use the lowest dose of corticosteroids that controls the stromal inflammation, and
consider prophylactic topical antiviral medications to prevent epithelial infection. Depending upon the etiology of IK, the patient may need very low doses of topical
corticosteroids indefinitely. Topical cycloplegia and frequent lubrication will increase patient comfort. Because IK can result from a variety of causes, conduct a diagnostic evaluation. If
you discover the underlying etiology, direct medical treatment toward the underlying cause should accompany topical corticosteroid treatment. Medical evaluation should
include FTA-ABS or MHA-TP to evaluate for syphilis, PPD (purified protein derivative) and chest X-rays to examine for tuberculosis, Lyme titer for Lyme disease, and rheumatoid factor and antinuclear antibodies to rule out collagen
vascular disease. However, if a patient develops IK on the same side as a prior episode of either HSV or HZV, and nothing in the patient's medical history points to other possible etiologies, no further work-up is necessary.1
Herpetic Stromal Disease
Stromal inflammation in herpes simplex is common; it was the predominant disease type in one study.14 Herpes simplex infections can result in the formation of
Wessely's immune rings in the peripheral cornea, manifesting as partial or complete circular white rings of infiltrate in the anterior stroma.12,15 This immune response,
which is not strictly limited to herpetic infections, is an antibody-mediated change incited by highly antigenic but non-infectious viral by-products.12
Limbal vasculitis (limbitis) manifests as intense hyperemia and edema of limbal tissues. Limbitis results from deposits of immune complexes in the vasculature and
leads to localized tissue inflammation. Dellen may form in severe cases.12,15 IK in herpes simplex presents as single or multiple patches of white necrotic infiltrate.
These stromal inflammatory reactions can be difficult to differentiate from bacterial and fungal keratitis. Herpetic IK runs an indolent course and the epithelium will be
intact; bacterial and fungal keratitis are very aggressive and both will have epithelial ulceration.12,15,16 During the acute phase of active herpetic IK, concurrent stromal vascularization will
develop. The vascularization can involve any layer of the stroma and increases throughout the course of the disease. The infiltration in herpetic IK runs an indolent
course through several months and will eventually limit itself. This form of stromal infiltration results from antigen-antibody-complement-mediated immune disease. Left
untreated, herpetic IK will ultimately result in dense corneal scarring and residual vascularization.12,15,16 A more severe form of herpetic stromal disease is necrotizing stromal keratitis. This
manifests as a dense yellow-white cheesy infiltration within the stroma. The full stromal thickness may be infiltrated and typically follows recurrent herpetic disease.
Necrotizing stromal keratitis frequently results in epithelial deterioration, ulceration, edema and dense vascularization. These lesions have a chronic course and will lead
to profound corneal thinning with possible perforation.15,16 Herpes simplex stromal disease also commonly manifests as disciform keratitis. Patients will experience mildly decreased vision, modest pain, photophobia and
lacrimation. A delayed hypersensitivity reaction to HSV antigen causes disciform keratitis, which may occur without previous dendritic ulceration. The discrete
disc-shaped areas of focal stromal edema, either central or peripheral, readily distinguish disciform keratitis from herpetic IK and necrotizing stromal keratitis. Most
cases have a mild clinical appearance,15,16 with no stromal vascularization, and maintain epithelial integrity. In some severe cases, however, the edema may be
significant with subsequent folds in Descemet's membrane, bullous keratopathy, epithelial ulceration, stromal vascularization and corneal melting. Stromal inflammatory disease in herpes simplex and herpes zoster has a similar
etiology and appearance. Stromal IK and disciform keratitis similar to that found in h. simplex can also be found in h. zoster infections. These stromal changes are also
immune-mediated and do not result from direct viral infection. In h. zoster, stromal inflammatory disease typically follows epithelial disease and vesicular skin eruptions.
This may occur several months after the skin rash develops.17,18 H. zoster disciform keratitis can occur without previous skin eruption, but these cases are rare and appear to be associated with abnormal immunity.19
Management of herpetic stromal inflammatory disease is much more controversial than that of epithelial disease. Topical and oral antiviral therapy alone have been
disappointing.16,20-22 Antiviral medications appear to play a strictly prophylactic role against epithelial ulceration in this disease. Since the stromal disease in herpes infections is primarily immune-modulated,
anti-inflammatory therapy is most appropriate.12,15,16 Since necrotizing keratitis is the most severe form of herpetic stromal disease, your therapy must be aggressive.
Topical corticosteroids will quell the inflammatory response. Again, use the least amount of steroid that effectively relieves symptoms and suppresses inflammation
(e.g. prednisolone acetate 0.125 percent or 1 percent 4-8 times per day). Use concurrent topical prophylactic antiviral therapy if you use steroids. If possible, begin
prophylactic antiviral therapy a day or two before introducing the corticosteroids in necrotizing stromal keratitis. If the epithelium ulcerates during therapy, then discontinue or reduce corticosteroids.
An alternative would be to discontinue topical corticosteroids and switch to oral prednisone (with topical antiviral medications) during active epithelial ulceration.16
Oral antiviral medications appear to have no beneficial role in the management of herpetic stromal disease unless the patient develops toxicity to topical prophylactic
antiviral medications. In this case, switch the patient to prophylactic oral antiviral therapy while treating with topical corticosteroids. Adjunctive cycloplegia is mandatory.
Herpetic disciform keratitis, stromal IK, Wessely's immune rings and limbitis all respond to anti-inflammatory therapy. However, conservatism is the key. In mild
cases of disciform keratitis and IK that do not involve the visual axis, topical lubrication and cycloplegia are often sufficient to manage the course of the
disease.12,15-17 However, if the inflammation and infiltration progress to involve the visual axis or develop vascularization, or if the patient's symptoms remain
uncontrolled, then consider adding topical corticosteroids at the lowest amount that will control the inflammation (e.g. prednisolone acetate 0.125 percent QID). If you do
use topical corticosteroids, also prescribe prophylactic antiviral medications at one-half the dosage used for an active epithelial disease (e.g. trifluridine 1 percent
4-5 times a day). Should epithelial ulceration develop during the course of topical corticosteroid therapy, reduce or discontinue the corticosteroids, or replace with oral
prednisone. Again, oral antiviral medications have no role unless the patient develops an allergic reaction to topical prophylactic antiviral medications.
Immunosuppression is the key to managing herpetic stromal inflammatory disease. A recent study has even shown that the immunosuppressant cyclosporin may have a role in treating this disease.23 Marginal Sterile Keratitis
In MSK, proliferation of bacteria (both normal flora and invading pathogens) in blepharitis creates a hostile environment as enzymatic exotoxins diffuse from the lid into the adjacent tear layer. When they contact the cornea, an immune sterile toxic response starts. The corneal epithelium and stromal keratocytes release inflammatory mediators. This draws inflammatory cells both from the now permeable limbal vasculature and the tear layer to the area of corneal damage. Inflammatory cells accumulate as a marginal infiltrate, which is typically small with a clear interval (lucid interval of Vogt) between the limbus and the edge of the infiltrate. Initially, the infiltrate will have an intact overlying epithelium. However, as inflammatory cells accumulate and neutralize the offending exotoxic hypersensitivity reaction, the collagenolytic enzymes from the inflammatory cells cause a corneotoxic reaction. This ultimately induces mild ulceration in the overlying epithelium. Despite the activity of bacterial exotoxins, this is a hypersensitivity immune reaction and not a direct bacterial infection. As such, corneal cultures of these lesions will be non-productive even though the causative agent may be Staphylococcus. The patient with MSK may be mildly symptomatic for ocular discomfort, photophobia or lacrimation, though many will be asympto- matic. MSK typically does not affect vision, and there is minimal or no anterior chamber reaction. Management begins with the eradication of the staphylococcal lid disease, with improved lid hygiene the least invasive measure. Because staphylococcal lid infection is strongly implicated, antibiosis specifically directed against this organism, along with lid hygiene, is ef- fective in reducing the offending antigen. The corneal lesion is an immunopathological stromal inflammation, so topical corticosteroids are indicated when simple antibiotic therapy fails to resolve the condition. If the overlying epithelium is disrupted, adjunctive antibiosis of the adjacent lid infection should prevent a secondary infection during topical corticosteroid therapy. Generally, the most effective management for MSK involves improved lid hygiene and the use of a topical antibiotic/steroid combination agent. Thygeson's Superficial Punctate Keratitis The patient will have recurrent episodes of photophobia and foreign body sensation. Vision may be modestly decreased depending upon involvement of the visual axis. There will not be associated conjunctival inflammation, nor will there be an anterior chamber reaction. The cornea will manifest multiple areas of stellate, round or oval intra- and sub-epithelial infiltrates. There will be variable epithelial staining and erosion overlying these lesions. There appears to be no trigger factor associated with outbreaks. The clinical presentation typically is bilateral, but may be markedly asymmetric. Management of Thygeson's SPK is generally conservative. Often topical lubrication will quell a patient's symptoms. If lubrication is insufficient, the lesions in Thygeson's SPK are readily steroid-responsive. However, corticosteroids may prolong the course of the disease while ameliorating symptoms. Topical antiviral medications such as trifluridine 1 percent have been used with some success and may provide a viable alternative to topical corticosteroids.33 Corneal Phlyctenulosis Limbal phlyctenules appear as pink-white elevated nodules that range from pinpoint to several millimeters in size. Their elevation differentiates them from the lesions in marginal keratitis. Limbal phlyctenules are often dull in color and appearance; they ulcerate and then heal with minimal scarring. Corneal phlyctenules tend to have a slightly more pinkish-fleshy hue than those in the limbus, and migrate across the cornea in a wedge shape. There will be attendant vascularization. Corneal phlyctenulosis has more serious sequelae, with stromal scarring and possible vision loss if the visual axis is involved. Corneal perforation is possible in severe cases.34 Limbal phlyctenulosis is typically only minimally symptomatic and may be asymptomatic. Symptoms consist of mild injection and foreign body sensation. Corneal phlyctenulosis, however, may present with significant ocular irritation, photophobia and lacrimation. Like marginal keratitis, phlyctenulosis is believed to be a sterile immunological reaction to bacterial antigens,35 specifically a type-4 cell-mediated hypersensitivity reaction. The most common antigen is Staphylococcus aureus. Presume this is the agent in mild cases of limbal phlyctenulosis. Historically the presence of phlyctenules has been associated with tuberculosis,36 but this as a causative agent has become less common. However, in cases of severe corneal phlyctenulosis with vascularization, TB evaluation with chest X-rays and PPD is strongly indicated, especially if the history includes travel to an endemic area, recurrent anterior uveitis, choroiditis or persistent cough. However, there is a report of corneal phlyctenulosis as the sole manifestation of undiagnosed tuber- culosis. So there doesn't need to be associated findings for you to pursue this diagnosis. Begin treatment of phlyctenulosis first by addressing the underlying causative agent. In the vast majority of cases, this will be S. aureus blepharoconjunctivitis, which should be treated with diligent lid hygiene, topical antibiotics and, in severe cases, oral antibiotics. Because this is an inflammatory condition, topical corticosteroids are definitely indicated. This is especially true of tuberculosis-related corneal phlyctenules, which may be exceedingly difficult to control. Phlyctenulosis, both corneal and limbal, tends to be recurrent, even when treated with steroids. This may lead to progressive scarring with potentially high ocular morbidity. Ocular Rosacea The most common ocular manifestations are non-specific foreign body sensation, dryness, grittiness, burning, tearing, redness and diffuse punctate epitheliopathy affecting the lower two-thirds of the cornea. This disruption of corneal integrity can lead to corneal infiltration, ulceration, neovascularization and scarring.38,39 In severe cases there can be thinning, descemetocele formation and corneal melting.40 The meibomian glands are modified sebaceous glands, and since acne rosacea involves sebaceous glands, it's not uncommon to find meibomian gland dysfunction. This can lead to tear film destabilization and, ultimately, secondary dry eye and subsequent findings. Diagnosis of ocular rosacea is easy to make when there's simultaneous involvement of the facial skin. However, the skin lesions may not be severe or even present at all. In these cases, the diagnosis is more tenuous. Suspect ocular rosacea in patients with chronic, recalcitrant superficial punctate epitheliopathy or with chronic complaints of ocular irritation that you cannot ascribe to another cause. Management involves fastidious lid hygiene with warm compresses and manual expression of the meibomian glands. Topical antibiotic ointments effective against Staph. can prevent bacterial overgrowth. Low doses of topical steroids should also be employed to manage the corneal inflammation and reduce scarring. Oral tetracycline (250mg QID) or doxycycline (100mg QID) for 12 weeks has improved the signs and symptoms of ocular rosacea.39 In cases of nondescript eye irritation and recalcitrant epitheliopathy, a therapeutic trial of oral doxycycline may confirm a diagnosis of ocular rosacea. Comanagement with a dermatologist is recommended because the corneal changes in ocular rosacea are potentially blinding.
Dr. Sowka is an associate professor at Nova Southeastern University College of Optometry in Fort Lauderdale, Fla., where he teaches glaucoma and retinal disease. He is also chief of the university's
Eye Institute Primary Care Clinic. Dr. Kabat is an associate professor there and director of the externship program. They are co-authors of Review of Optometry's Annual Handbook of Ocular Disease Management.
1. Schwartz GS, Harrison AR, Holland EJ. Etiology of immune stromal (interstitial) keratitis. Cornea 1998;17(3):278-81. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| | | | | | | |
