AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Atopic keratoconjunctivitis (AKC) is a relatively uncommon but potentially blinding ocular condition. In 1952, Hogan described AKC as a bilateral conjunctivitis occurring in 5 male patients with atopic dermatitis. Originally described to flare with worsening dermatitis, Foster et al noted that some patients' ocular involvement evolves independent of dermatitis.

AKC is associated with a 95% prevalence of concomitant eczema and an 87% prevalence of asthma. Other than AKC, common ocular atopic phenomena include allergic conjunctivitis, giant papillary conjunctivitis, and vernal keratoconjunctivitis.

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, they 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 AKC. During exacerbations, patients have increased tear and serum IgE levels and increased numbers of circulating B cells; T-cell levels are depressed.

Frequency

International

Atopy affects 5-20% of the general population. AKC occurs in 20-40% of individuals with atopic dermatitis.

Mortality/Morbidity

Decreased vision and blindness result from chronic superficial punctate keratitis, persistent epithelial defects, corneal scarring or thinning, keratoconus, cataracts, and symblepharon formation. The use of corticosteroids to medically treat AKC can further promote the development of cataracts, glaucoma, and secondary corneal infections.

Sex

This condition is more prevalent in men than in women.

Age

Peak age of incidence is in persons aged 30-50 years. The age range is from the late teenaged years to 50 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Look for the following in past medical history:

• Chronic or chronically relapsing atopic disease
• • Dermatitis
  • Asthma
  • Rhinitis
• Ocular symptoms with little or no seasonal variation (as opposed to vernal conjunctivitis that is seen only in warm weather)
• • Itching
  • Tearing
  • Ropy discharge
  • Burning
  • Photophobia
  • Decreased vision

Physical

• Periorbita - Dennie-Morgan folds (linear lid folds secondary to chronic eye rubbing) and Hertoghe sign (absence of lateral eyebrows)
• Lids - Thickening and tylosis, crusting, edema, fissures, ptosis, and staphylococcal blepharitis
• Conjunctiva
• • Small- or medium-sized papillae, hyperemia, edema, excessive mucin, and limbal Trantas dots (clusters of necrotic eosinophils, neutrophils, and epithelial cells)
  • Formation of keratinization, cicatrization, and symblepharon in advanced disease
• Cornea
• • Punctate epitheliopathy and keratitis, persistent epithelial defects, shield-shaped ulcers, anterior stromal scarring, and micropannus
  • Extensive peripheral corneal vascularization in later stages
  • Higher incidence of keratoconus (16%) and recurrent herpes simplex keratitis associated with AKC
• Lens - Posterior or anterior subcapsular shield-shaped cataracts
• Fundus - Degenerative vitreous changes and retinal detachment

Causes

See Pathophysiology.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Corneal thinning and perforation
Secondary corneal infection
Steroid-response glaucoma
Vernal conjunctivitis (Large conjunctival papillae are seen under the upper eyelid in palpebral vernal or along the limbus in limbal vernal.)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No specific laboratory testing is mandated.
• Serum IgE levels are usually elevated during exacerbations; however, skin testing is not helpful.

Procedures

• Conjunctival biopsy can help differentiate AKC from cicatricial pemphigoid.

Histologic Findings

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

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Prophylaxis
• • Topical mast cell stabilizers reduce the incidence of exacerbations.
  • Topical and oral antihistamines in combination with efforts to reduce or eliminate allergen exposure are invaluable for long-term control.
• Exacerbations
• • Intensive topical steroids are used for short-term flare-ups, tapering according to clinical response.
  • 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 possible alternate therapy in situations where steroid use needs to be minimized. 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.

Surgical Care

• Cataract surgery with intraocular lens implantation is associated with favorable outcomes.
• Penetrating keratoplasty for corneal scarring is associated with a higher than average incidence of graft failure. Ocular surface inflammation should be well controlled prior to surgery.
• Plasmapheresis has been suggested as a successful adjunct therapy for patients with high IgE levels.

Consultations

Comanagement with an allergist is indicated for optimal long-term control.

Activity

Reduction or elimination of inciting environmental allergens is necessary for optimal prophylaxis.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Mast cell stabilizers and antihistamines are mainstays of prophylactic therapy. Antihistamines, steroids, and other immunosuppressives are used for immediate control of symptoms. For additional information, see PDR.net.

Drug Category: Topical mast cell stabilizers

Inhibit degranulation of sensitized mast cells upon exposure to specific antigens.

Drug Name	Lodoxamide tromethamine 0.1% (Alomide)
Description	Stabilizes mast cells and inhibits increased vascular permeability, which is associated with 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.
Adult Dose	1-2 gtt qid
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not for injection; patients often experience transient burning or stinging from instillation; soft contact lens wearers should refrain from using them while under treatment

Drug Name	Nedocromil sodium 2% (Alocril)
Description	Interferes with mast cell degranulation, specifically with release of leukotrienes and platelet activating factor.
Adult Dose	1-2 gtt bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adverse events include ocular irritation/burning, headache, nasal congestion, and unpleasant taste in 10-40% of patients

Drug Name	Pemirolast potassium 0.1% (Alamast)
Description	Interferes with mast cell degranulation and mast cell stabilizer in both early and late phases.
Adult Dose	1-2 gtt qid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	For topical ophthalmic use only (not for injection or oral use); instruct patients who wear soft contact lenses and whose eyes are not red to wait >10 min after applying drops to insert contact lenses

Drug Category: Topical antihistamines

Act by competitive inhibition of histamine at the H1 receptor. For prophylaxis and symptomatic relief.

Drug Name	Ketotifen fumarate 0.025% (Zaditor)
Description	Selective H1 histamine receptor antagonist and mast cell stabilizer. Inhibits release of mediators from cells involved in hypersensitivity reactions.
Adult Dose	1-2 gtt in affected eye(s) bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	For topical ophthalmic use only; not for treatment of contact lens–related inflammation; wait 10 min before inserting lenses after ketotifen use; do not contaminate dropper tip or solution when placing drops in eyes; in controlled clinical studies, minor conjunctival injection, headaches, and rhinitis were reported at an incidence of 10-25%

Drug Name	Azelastine hydrochloride 0.05% (Optivar)
Description	Antihistamine and mast cell stabilizer.
Adult Dose	1 gtt in affected eye(s) bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Instruct patients who wear soft contact lenses and whose eyes are not red to wait >10 min after applying drops to insert contact lenses; transient eye burning and stinging, headaches, and bitter taste were reported in 10-30% of patients

Drug Name	Epinastine hydrochloride 0.05% (Elestat)
Description	H1 antihistamine and mast cell stabilizer.
Adult Dose	1 gtt in affected eye(s) bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Ocular reactions of burning sensation, folliculosis, hyperemia, and pruritus reported in 1-10% of patients; nonocular reactions of cold symptoms and upper respiratory infections seen in 10% of patients

Drug Category: Corticosteroids

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

Drug Name	Fluorometholone 0.1%, 0.25% (FML, FML Forte)
Description	Inhibits edema, fibrin deposition, capillary dilation and phagocytic migration of acute inflammatory response and capillary proliferation, collagen deposition, and scar formation. Used topically, it can elevate IOP and cause steroid-response glaucoma. 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 wk. The ultimate magnitude of the rise was equivalent.
Adult Dose	1 gtt bid/qid; may increase prn depending on clinical response
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hypertension; known to cause cataract formation with long-term use; suspect fungal invasion in any persistent corneal ulceration where a corticosteroid has been used or is in use (obtain fungal cultures when appropriate)

Drug Name	Loteprednol etabonate 0.5%, 0.2% (Lotemax, Alrex)
Description	Structurally similar to other corticosteroids, but the number 20 position ketone group is absent. Highly lipid soluble, which enhances cell penetration. Undergoes a predictable transformation to an inactive carboxylic acid metabolite. Shown to be less effective than prednisolone acetate 1% in two 28-d controlled clinical studies in acute anterior uveitis; 72% of patients treated with Lotemax experienced resolution of anterior chamber cells compared to 87% of patients treated with prednisolone acetate 1%. Incidence of patients with clinically significant increases in IOP (>10 mm Hg) was 1% with Lotemax and 6% with prednisolone acetate 1%.
Adult Dose	1 gtt qid; may increase to q1h during first wk prn for clinical response
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hypertension; known to cause cataract formation with long-term use; suspect fungal invasion in any persistent corneal ulceration where a corticosteroid has been used or is in use (obtain fungal cultures when appropriate)

Drug Category: Immunosuppressants

Used as adjunctive or alternative treatment in situations where steroid use is ineffective or requires minimization.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

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

Deterrence/Prevention

• Efforts to reduce or eliminate environmental allergen exposure must be addressed for optimal long-term control.

Complications

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

Prognosis

• AKC may result in decreased vision or blindness from corneal complications.
• Proper prophylactic measures, prompt effective treatment of exacerbations, and well-timed elective surgical intervention can reduce the incidence of poor vision and blindness.

Patient Education

• For excellent patient education resources, visit eMedicine's Eye and Vision Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education articles Pinkeye, Eye Allergies, and Eczema.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to periodically examine patients with AKC

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Atopic keratoconjunctivitis. Limbal Trantas dots.
	View Full Size Image
Media type:  Photo

Media file 2:  Atopic keratoconjunctivitis. Corneal shield ulcer.
	View Full Size Image
Media type:  Photo

Media file 3:  Atopic keratoconjunctivitis. Symblepharon.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Akpek EK, Dart JK, Watson S. A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis. Ophthalmology. Mar 2004;111(3):476-82. [Medline].
• Casey R, Abelson MB. Atopic keratoconjunctivitis. Int Ophthalmol Clin. Spring 1997;37(2):111-7. [Medline].
• Foster CS, Calonge M. Atopic keratoconjunctivitis. Ophthalmology. Aug 1990;97(8):992-1000. [Medline].
• Hingorani M, Moodaley L, Calder VL, et al. A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis. Ophthalmology. Sep 1998;105(9):1715-20. [Medline].
• Power WJ, Tugal-Tutkun I, Foster CS. Long-term follow-up of patients with atopic keratoconjunctivitis. Ophthalmology. Apr 1998;105(4):637-42. [Medline].

Article Last Updated: Sep 29, 2006