Signs and Symptoms

Marginal keratitis is defined as a peripheral corneal inflammatory response.1-4 The condition is also known as sterile keratitis, infiltrative keratitis, peripheral keratitis, peripheral ulcerative keratitis, contact lens-induced peripheral ulcer (CLPU) and contact lens-related infiltrates. It can follow chronic exposure to an antigen (e.g., make-up, chemical exposure, pathogens), a chronic mechanical stimulus (e.g., debris, eyelid or eyelash), induced hypoxia (e.g., contact lens related) or can be a sequelae of vasculitic systemic disease (e.g., engraftment syndrome after hematopoietic stem cell transplantation, leukocytoclastic vasculitis).1-14

Patients with marginal keratitis may range in presentation from completely asymptomatic to severely symptomatic, depending on the extent and duration of the reaction.

When present, symptoms are graded as mild, moderate and severe, and may also be acompanied by ocular discomfort (e.g., burning, foreign body sensation, grittiness), photophobia and chronic tearing.6 Vision generally remains unaffected.1-7

Typically, bulbar conjunctival injection is mild to absent. In the Fuchs’ variation, a pseudopterygium with mild corneal thinning may be noted.14 The palpebral conjunctiva may demonstrate subtle conjunctival chemosis.11-13 The key diagnostic sign is one or more focal areas of grayish, subepithelial infiltrate near the limbus, usually located in the inferior cornea and particularly where the cornea interacts with the lower eyelid margin.1,2,13-15 When the overlying epithelium is compromised, the defect is usually seen as an interrupted stippling much smaller than the area of infiltrate. This is in contradistinction to microbial keratitis, which demonstrates a continuous area of epithelial defect virtually equal to the area of stromal infiltrate.16

Characteristically, there are zones of unaffected limbal cornea.9 In rare instances, marginal keratitis may be accompanied by other inflammatory ocular sequelae, such as mild anterior uveitis or folds in Descemet’s membrane associated with corneal edema.

Blepharitis and its variants (seborrheic, psoriasiatic, acne rosacea, Demodex) are major contributors secondary to their effects on the lid margin.2,11,12,13,17-19

Patients with marginal keratitis may have a history of other ocular surface disease, such as chronic dry eye or allergic conjunctivitis. Inflammatory autoimmune disorders—including Terrien’s marginal degeneration, Stevens-Johnson syndrome, rheumatoid arthritis, granulomatosis with polyangiitis, Behçet’s disease and Churg-Strauss syndrome—are also known to produce marginal keratitis.1,2,8-12, 13,15,16,19-21


Classic marginal keratitis represents as a localized immune response, believed to be driven by antigen-antibody complexes that deposit in the peripheral corneal stroma.11,20-23 Generically, the mechanism is that an inflammatory process initiates a cascade that results in the influx of leukocytes and plasma molecules to the site of the tissue damage.1,24,25 The inciting etiology will dictate the specific cellular response.15,16,25-27

Initially, the overlying epithelium remains intact; however, as inflammatory cells accumulate to neutralize the offending reaction, collagenolytic enzymes released from these cells induce noninfectious ulceration (infiltrate in the presence of an overlying corneal break).15,28 Matrix metalloproteinase-9 (MMP-9) appears to be a prominent player in the initiation of the epithelial basement membrane degradation that precedes corneal ulceration.28

Historically, bacterial exotoxins from staphylococcal organisms are considered the primary etiology.11,13,15,20,22 While bacterial overgrowth associated with chronic blepharitis remains a significant cause of marginal keratitis, clearly not all cases are caused by microbial flora.4-9 Other causes include systemic autoimmune disorders, mechanical events and hypersensitivity reactions to foreign substances and topical drugs including phenylephrine, gentamicin, atropine, pilocarpine and dorzolamide.2,3-11,15,16,26,27

Corneal hypoxia and bacterial biofilm associated with soft contact lens wear represent yet another potential etiology, although in these instances clinicians tend to use the term contact lens-induced peripheral ulcer (CLPU).5


The treatment strategy for marginal keratitis must address both extinguishing the inflammatory response and removing or controlling the causative etiology.2-27 In cases where microbial flora are implicated, aggressive control of eyelid and ocular surface bacteria can be accomplished using topical and oral antibiotics.

Mechanical cleaning of the eyelids to soften and remove debris/microbes should be employed, using warm compresses and commercially available lid cleansers such as OcuSoft (Cynacon) or generic “no-more-tears” baby shampoos, two to four times daily.29

Metronidazole ointment BID along with oral ivermectin, dosed once and repeated in seven days if necessary, are indicated in cases of suspected Demodex infestation.30 In cases of rosacea (meibomian gland dysfunction), oral tetracycline 500mg BID PO, doxycycline 100mg BID PO or azythromicin (Z-pack) can be prescribed.31,32 Generic staphylococcal blepharitis can be treated with traditional topical fluoroquinolone antibiotic drops and or ointments QID.

Since inflammation is an integral portion of the entity’s histopathology, its mitigation can be accomplished with either topical antibiotic-steroid combination drops or ointments BID-QID or the addition of a topical steroid such as fluorometholone, prednisolone acetate, loteprednol etabonate or difluprednate to the topical antibiotic.2-27 Since topical steroids may increase intraocular pressure (IOP), any prolonged course should include IOP monitoring. In cases with significant anterior segment inflammation or symptoms, cycloplegia may be warranted.

Marginal keratitis associated with drug hypersensitivity necessitates discontinuing the noxious agent and controlling inflammation as aforementioned.26,27 Cases of contact lens-induced peripheral ulcer warrant temporarily discontinuing lens wear, protecting the cornea with a topical antibiotic or antibiotic-steroid combination and rehabilitating the ocular surface. Wear can continue following a reevaluation of the fit, lens material and disinfection system.5

Management options associated with systemic autoimmune diseases require a team approach. Correspondence with systemic specialists such as dermatology, infectious disease or rheumatology are critical.6-10,13,15,16 In these cases, the classic topical regimen will require oral or intravenous supplementation, including systemic corticosteroids and immunomodulating agents, to attack the underlying disease process.6-10

Clinical Pearls

Common examples of marginal keratitis are “sterile corneal infiltrates” or “sterile ulcerations” on the periphery of the cornea.

Marginal keratitis itself is not an infectious process. It is an inflammatory response to a local toxic (chemical or microbial), mechanical, hypoxic or systemic inflammatory stimulus.

The principal differential diagnoses for marginal keratitis include microbial keratitis, Mooren’s ulcer, Terrien’s marginal degeneration, and peripheral keratolysis (peripheral ulcerative keratitis—sometimes referred to as corneal melting).

Microbial keratitis, as opposed to marginal keratitis, is characteristically: (1) located centrally or paracentrally, (2) composed of a singular large lesion, (3) secondary to a unilateral process, (4) produces an aggravated inflammatory response (significant cell and flare seen in the anterior chamber), (5) can be very painful and (6) produces symptoms which include tearing, photophobia and decreased vision.

Mooren’s ulcer is a painful, rapidly progressive keratitis that results in generalized peripheral corneal thinning, sometimes leading to perforation.

Terrien’s degeneration is a bilateral, painless, progressive degeneration of the peripheral cornea occurring in the setting of an otherwise white and quiet eye.

Corneal scrapings and cultures in marginal keratitis are generally non-productive and unnecessary, even when the condition is associated with staphylococcal blepharitis. Cultures should only be considered if the condition does not improve within the first 48 to 72 hours of intervention.


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