Atopic Keratoconjunctivitis (AKC) 

Updated: May 29, 2019
Author: Anne Chang-Godinich, MD, FACS; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Atopic keratoconjunctivitis (AKC) is a relatively uncommon but potentially blinding ocular condition. In 1952, Hogan described this disease as a bilateral conjunctivitis occurring in 5 male patients with atopic dermatitis. Originally reported to flare with worsening dermatitis, atopic keratoconjunctivitis in some patients evolves independent of dermatitis.[1]

Atopy affects 5-20% of the general population. Atopic keratoconjunctivitis not only occurs in 20-40% of individuals with atopic dermatitis, it is associated with a 95% prevalence of concomitant eczema and an 87% prevalence of asthma. This condition is more prevalent in men than in women, and the peak age of incidence is in persons aged 30-50 years (range, late teens to 50 y)

Other than atopic keratoconjunctivitis, common ocular atopic phenomena include allergic conjunctivitis, giant papillary conjunctivitis, and vernal keratoconjunctivitis.

For patient education information, see Eye and Vision Center and Skin, Hair, and Nails Center, as well as Pinkeye, Eye Allergies, and Eczema.

See also the following:

  • Keratitis Sicca

  • Epidemic Keratoconjunctivitis

  • Superior Limbic Keratoconjunctivitis

  • Allergic Conjunctivitis

  • Bacterial Conjunctivitis

  • Emergent Treatment of Acute Conjunctivitis

  • Giant Papillary Conjunctivitis

  • Viral Conjunctivitis

Pathophysiology

Atopy refers to hypersensitivity in patients with familial histories of allergic disease. Individuals with atopy often have environmental allergies, allergic asthma, rhinitis, and atopic dermatitis or eczema. Less commonly, these individuals exhibit food allergies, urticaria, and nonhereditary angioedema. Immunoglobulin E (IgE) is the serum mediator of the exuberant responses.

Hypersensitivity reactions associated with types I and IV contribute to the inflammatory changes of the conjunctiva and the cornea that are found in atopic keratoconjunctivitis (AKC). During exacerbations, patients have increased tear and serum IgE levels and increased numbers of circulating B cells, whereas T-cell levels are depressed.

Prognosis

Atopic keratoconjunctivitis (AKC) may result in decreased vision or blindness from corneal complications, such as chronic superficial punctate keratitis, persistent epithelial defects, corneal scarring or thinning, keratoconus, cataracts, and symblepharon formation.[2]

Complications result from persistent surface keratopathy, corneal scarring or thinning, keratoconus, cataracts, and symblepharon formation. In addition, medical treatment with corticosteroids can further promote the development of cataracts, glaucoma, and secondary corneal infections.

Proper prophylactic measures, prompt effective treatment of exacerbations, and well-timed elective surgical intervention can reduce the incidence of poor vision and blindness.

Patients should be observed every few days or weeks until the ocular surface disease is stable. Moreover, when medically treating patients with steroids or immunosuppressants, a regular interval survey for drug-related adverse effects and complications is indicated.

 

Presentation

History

When evaluating a patient with suspected atopic keratoconjunctivitis (AKC), look for the following in past medical history:

  • Chronic or chronically relapsing atopic disease, including dermatitis, asthma, and/or rhinitis

  • Ocular symptoms with little or no seasonal variation (as opposed to vernal conjunctivitis that is seen only in warm weather), including itching, tearing, ropy discharge, burning, photophobia, and/or decreased vision

Physical Examination

On examination, evaluate the following areas of the affected eye(s): the periorbital region, eyelid, conjunctiva, cornea, lens, and fundus.

Periorbital region

Evaluate this area for Dennie-Morgan folds (linear lid folds secondary to chronic eye rubbing) and the Hertoghe sign (absence of lateral eyebrows).

Eyelid(s)

Evaluate the eyelid(s) for thickening and tylosis, crusting, edema, fissures, ptosis, and staphylococcal blepharitis.

Conjunctiva(e)

Evaluate the conjunctiva(e) for small- or medium-sized papillae, hyperemia, edema, excessive mucin, and limbal Trantas dots (clusters of necrotic eosinophils, neutrophils, and epithelial cells) (see the first image below). Keratinization, cicatrization, and symblepharon (adhesion of the palpebral conjunctiva to the bulbar conjunctiva) develop in advanced disease (see the second the image below).

Atopic keratoconjunctivitis. Limbal Trantas dots c Atopic keratoconjunctivitis. Limbal Trantas dots can be seen in this image.
Atopic keratoconjunctivitis. This image depicts a Atopic keratoconjunctivitis. This image depicts a symblepharon.

Cornea(s)

Evaluate the cornea(s) for punctate epitheliopathy and keratitis, persistent epithelial defects, shield-shaped ulcers (as shown in the following image), anterior stromal scarring, and micropannus. Extensive peripheral corneal vascularization occurs in later stages. Note that a higher incidence of keratoconus (16%) and recurrent herpes simplex keratitis is associated with atopic keratoconjunctivitis.

Atopic keratoconjunctivitis. A corneal shield ulce Atopic keratoconjunctivitis. A corneal shield ulcer is illustrated in this image.

Lens(es)

Posterior or anterior subcapsular shield-shaped cataracts are characteristic in atopic keratoconjunctivitis.

Fundus(i)

Evaluate the fundus(i) for degenerative vitreous changes and retinal detachment.

 

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of atopic keratoconjunctivitis include corneal thinning and perforation, secondary corneal infection, steroid-response glaucoma, as well as vernal conjunctivitis.

In vernal conjunctivitis, large conjunctival papillae are seen under the upper eyelid in the palpebral vernal or along the limbus in limbal vernal. In addition, vernal conjunctivitis is seen only in warm weather, whereas atopic keratoconjunctivitis tends to present with ocular symptoms that have little or no seasonal variation.

Differential Diagnoses

 

Workup

Approach Considerations

No specific laboratory testing is necessary for atopic keratoconjunctivitis (AKC). Although serum immunoglobulin E (IgE) levels are usually elevated during exacerbations, skin testing is not helpful. However, conjunctival biopsy can help to differentiate atopic keratoconjunctivitis from cicatricial pemphigoid.

Conjunctival Biopsy and Histology

Conjunctival biopsy specimens reveal excessive eosinophils, mast cells, and goblet cells. These specimens can also help to histologically differentiate atopic keratoconjunctivitis from cicatricial pemphigoid by the presence of basement membrane antibodies or complement components in cicatricial pemphigoid.

Confocal microscopy studies of the cornea show lower density of basal epithelial cells, thickening of stromal nerves, and severe inflammatory cells in proximity to nerve fibers.[3]

 

Treatment

Approach Considerations

Proper prophylactic measures, prompt effective treatment of exacerbations, and well-timed elective surgical intervention can reduce the incidence of poor vision and blindness.

Mast cell stabilizers and antihistamines are the mainstays of prophylactic therapy. Antihistamines, steroids, and other immunosuppressives are used for immediate control of symptoms. Comanagement with an allergist is indicated for optimal long-term control.

Plasmapheresis has been suggested as a successful adjunct therapy for patients with high immunoglobulin E (IgE) levels.

Prophylaxis and Management of Exacerbations

Efforts to reduce or eliminate environmental allergen exposure must be addressed for optimal long-term control of atopic keratoconjunctivitis (AKC). These efforts in combination with topical and oral antihistamines are invaluable in controlling this condition.[1, 4]

Topical mast cell stabilizers reduce the incidence of exacerbations. Intensive topical steroids are used for short-term flare-ups, tapering according to clinical response.[1, 4]

In some situations, more aggressive or steroid-sparing treatment may be indicated. Topical 0.05% or 2% cyclosporine suspended in oil used 4-6 times per day is proven to be effective for exacerbations and may be considered as an adjunct or as possible alternate therapy in situations in which steroid use needs to be minimized.[5, 6, 7]

Systemic cyclosporine (5 mg/kg/d) has been shown to be effective in inducing remission. Low-dose maintenance therapy (5 mg/kg q5d) may be required in refractory cases.[8]

It is important to keep in mind that when medically treating patients with steroids or cyclosporine, patients must be monitored regularly for drug-related adverse effects and complications.

T-lymphocyte immunomodulators, such as tacrolimus, have been used in refractory cases with good response. These agents are administered systemically[9] or topically in ointment form.[10] Internationally, application of tacrolimus dermatologic ointment in children and adults has shown promise as an effective steroid-sparing alternative.[11, 12, 13]

Elective Surgical Intervention

Atopic keratoconjunctivitis (AKC) is primarily managed medically. However, in some cases in which inflammation is well controlled, elective surgery may be of benefit. Cataract surgery with intraocular lens implantation has been associated with favorable outcomes.[2] However, penetrating keratoplasty for corneal scarring is associated with a higher than average incidence of graft failure. Ocular surface inflammation should be well controlled before surgery.

 

Medication

Medication Summary

The goals of pharmacotherapy in the treatment of atopic keratoconjunctivitis are to reduce morbidity and to prevent complications, such as significant keratopathy, conjunctival fornix foreshortening, and corneal scarring or thinning requiring penetrating keratoplasty.

Mast cell stabilizers and antihistamines are the mainstays of prophylactic therapy. Antihistamines, steroids, and other immunosuppressives are used for immediate control of symptoms.

When medically treating patients with steroids, cyclosporine, or tacrolimus, a regular interval survey for drug-related adverse effects and complications is indicated.

For additional information, see PDR.net.

Topical mast cell stabilizers

Class Summary

Topical mast cell stabilizers inhibit degranulation of sensitized mast cells upon exposure to specific antigens.

Lodoxamide tromethamine 0.1% (Alomide)

Lodoxamide stabilizes mast cells and inhibits increased vascular permeability, which is associated with immunoglobulin E (IgE) and antigen-mediated reactions. Alomide has been reported to prevent calcium influx into mast cells upon antigen stimulation without intrinsic anti-inflammatory, antihistamine, or vasoconstrictive effects.

Nedocromil sodium 2% (Alocril)

Nedocromil interferes with mast cell degranulation, specifically with the release of leukotrienes and platelet activating factor.

Topical antihistamines

Class Summary

Topical antihistamine agents act by competitive inhibition of histamine at the H1 receptor. These medications are used for prophylaxis and symptomatic relief.

Ketotifen fumarate 0.025% (Zaditor, Alaway, Claritin Eye, Zyrtec Itchy Eye)

Ketotifen is a selective H1 histamine receptor antagonist and mast cell stabilizer that acts by inhibiting the release of mediators from cells involved in hypersensitivity reactions.

Olopatadine hydrochloride 0.1% (Patanol, Pataday)

Olopatadine inhibits histamine release through both selective H1 histamine receptor antagonism and less-specific mast cell stabilization.

Epinastine hydrochloride 0.05% (Elestat)

Epinastine is another H1 antihistamine and mast cell stabilizer. As with azelastine, the usual dose is 1 drop in the affected eye(s) twice daily.

Azelastine hydrochloride 0.05% (Optivar)

Azelastine is both an antihistamine and mast cell stabilizer. The usual dose is 1 drop in the affected eye(s) twice daily.

Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.

Loteprednol etabonate 0.5%, 0.2% (Lotemax, Alrex)

Loteprednol is structurally similar to other corticosteroids, but the number 20 position ketone group is absent. This agent is highly lipid soluble, which enhances cell penetration, and undergoes a predictable transformation to an inactive carboxylic acid metabolite.

Loteprednol was shown to be less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis; 72% of patients treated with Lotemax experienced resolution of anterior chamber cells compared with 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in intraocular pressure (>10 mm Hg) was 1% with Lotemax and 6% with prednisolone acetate 1%.

Fluorometholone 0.1%, 0.25% (FML, FML Forte)

Fluorometholone inhibits edema, fibrin deposition, capillary dilatation, and phagocytic migration of acute inflammatory response and capillary proliferation, collagen deposition, and scar formation. Used topically, this agent can elevate intraocular pressure (IOP) and cause steroid-response glaucoma. However, in clinical studies of documented steroid responders, fluorometholone demonstrated a significantly longer average time to produce a rise in IOP than dexamethasone phosphate. In a small percentage of individuals, a significant rise in IOP occurred within 1 week. The ultimate magnitude of the rise was equivalent.

Prednisolone acetate 1%, 0.12% (Pred Forte, Pred Mild)

On the basis of weight, prednisolone has 3-5 times the anti-inflammatory potency of hydrocortisone. Glucocorticoids inhibit edema, fibrin deposition, capillary dilatation and proliferation, phagocytic migration of the acute inflammatory response, deposition of collagen, and scar formation.

Difluprednate ophthalmic (Durezol)

Difluprednate ophthalmic is an ophthalmic corticosteroid indicated for inflammation and pain associated with ocular surgery. It is available as a 0.05% ophthalmic emulsion.

Immunosuppressants

Class Summary

Immunosuppressant agents are used as adjunctive or alternative treatment in situations in which steroid use is ineffective or requires minimization.

Cyclosporine (Restasis)

The exact mechanism of the immunosuppressive activity of cyclosporine is unknown, but preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle has been suggested.