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Atopic keratoconjunctivitis (AKC) is a chronic inflammatory disease of eye that affects patients with atopic dermatitis.
AKC was first described in 1952 by Hogan, who described five cases of atopic eczema associated with bilateral keratoconjunctivitis. Peak incidence is between 30-50 years old. It is characterized by bilateral, non-infectious inflammation of the conjunctiva.
Atopic dermatitis is a common chronic inflammatory skin disease that affects affects up to 15-20% of children and 1-3% of adults worldwide that presents as acute exacerbations of eczematous pruritic lesions of the skin. It is estimated that 25-40% of patients with atopic dermatitis suffer from AKC .
By definition, AKC is the chronic ocular surface inflammation suffered by patients with atopic dermatitis.
The pathophysiology is incompletely understood, but likely represents a combination of type I (IgE mediated) and type IV (delayed) hypersensitivity reactions. This involves the release of cytokines by mast cells, eosinophils, T cells and conjunctival epithelial cells. This release of allergic mediators leads to activation of T helper cells and chronic mast cell degranulation. AKC patients have also been shown to have decreased corneal sensitivity and conjunctival goblet cell density compared to controls.
AKC is a multifactorial disease with genetic and environmental risk factors. The strongest associations are genetic predisposition for poor skin barrier function and dysregulation of the immune system, asthma, allergic rhinitis and environmental allergens. The presence of food allergies and sensitivities in infancy and childhood is associated with a more severe form of atopic dermatitis. Allergy and sensitivity to pollen, pets and dust mites have also been associated with AKC.
Environmental factors such as climate, diet, urban living (including pollution exposure), tobacco smoke, duration of breastfeeding during infancy and obesity have been suggested as risk factors for AKC. It has also been proposed that antibiotic use may increase the risk of developing atopic disease via alterations to the gut microbiome.
Histology of AKC typically shows proliferation of goblet cells, invasion of eosinophils and mast cells into the epithelium as well as mononuclear cell infiltrate in the substantia propria. Conjunctival epithelium of AKC patients shows increased levels of T cells, T-helper cells, macrophages and dendritic cells.
Primary prevention involves reducing the probability of disease in patients that do not have clinically evident disease. Breastfeeding has shown to be a protective factor, particular before 3 months of age. Additionally, prenatal and postnatal probiotics could reduce the incidence of atopic disease by as much as 30%. Dietary supplementation with vitamins and minerals has been studied, but has not shown any benefit.
The diagnosis of atopic keratoconjunctivitis is largely clinical, relying on history and exam findings.
A family history of allergies, asthma, urticaria, and/or hay fever is often present. Typically, patients have atopic dermatitis or eczema since childhood, with ocular symptoms developing later in life. Mean onset of ocular symptoms is 38 years.
The chief symptom of AKC is intense, bilateral itching of the conjunctiva, eyelids and periorbital skin. Tearing, burning, photophobia and blurry vision are commonly encountered symptoms. Patients with AKC can have copious mucoid discharge, often described as rope-like.
- Eyelids and periorbita: The eyelids and periorbital skin will almost always show evidence of eczematous dermatitis (erythematous, thickened dry skin with blistered patches). Eyelid findings include tylosis (thickening of the tarsal border of the eyelid) with crusting and scaling. Meibomian gland disease is very common in patients with AKC. Other lid findings often encountered are ectropion, trichiasis and madarosis.
- Conjunctiva: The conjunctiva is hyperemic and edematous, with prominent tarsal papillae (papillary conjunctivitis). Mucoid discharge is often present. Severe conjunctival disease can result in scarring and symblepharon. Horner-Trantas dots may or may not be present.
- Cornea: Corneal involvement is frequent, and can range from punctate epithelial erosions to ulcers and even perforation. Peripheral vascularization and pannus are common.
- Anterior Segment: Anterior and posterior subcapsular cataracts are common.
Clinical diagnosis is based mainly on history and exam findings, though adjunctive diagnostic procedures and lab tests can aid in diagnosis and assessing severity of disease. Many of these tests require equipment not readily available to most ophthalmologists.
Serum IgE and skin prick testing is non-specific, but can be helpful in establishing that a patient has atopic disease. IgE levels in tears have been shown to correlate with clinical severity of allergic eye disease.
Brush cytology, which involves taking scrapings from the tarsal conjunctiva, can quantify levels of inflammatory cells such as eosinophils and neutrophils. It has been show to correlate with the amount of corneal damage. Confocal scanning laser microscopy has been described as a less invasive means of evaluating the ocular surface of AKC patients by identification of inflammatory cell densities. A significant correlation was found between the extent of inflammation as determined via brush cytology and that found by in-vivo confocal microscopy.
Conjunctival biopsy is rarely used to assist in diagnosing AKC. As above, on pathology, mast cell infiltration of the conjunctival epithelium can be seen.
Clinically, AKC is very similar to vernal keratoconjunctivitis (VKC), and there is controversy regarding classification of the two diseases. It has been proposed that VKC is a childhood form of AKC that evolves into AKC in adulthood. However, VKC can be present without signs of atopic disease. VKC is generally regarded to end at puberty, and by definition symptoms and disease severity fluctuate with seasons. Giant papillary reaction is more common in VKC. Atopic disease is a year-round condition. Though AKC peaks in adults, it can be present in childhood.
- Vernal keratoconjunctivitis
- Seasonal allergic conjunctivitis
- Giant papillary conjunctivitis
- Phlyctenular keratoconjunctivitis
- Toxic conjunctivitis
- Infections conjunctivitis (esp. trachoma)
- Ocular rosacea
The purpose of treatment in AKC is to improve symptoms, limit exacerbations and prevent complications/sequelae that lead to vision loss. It is also important to balance this with limiting side effects of treatment.
Involvement of other specialists such as dermatologists and allergists is essential to successful management. Attention should be payed to limiting environmental factors that exacerbate disease. This can include use of hypoallergenic bedding, elimination of pets when necessary, use of air filtering devices and dietary changes in cases of food sensitivity.
Topical Therapy: Mild disease can be treated similarly to other allergic eye disease, with emphasis placed on hand hygiene, cold compresses and topical mast cells stabilizers (olopatadine 0.1% or lodoxamide 0.1%) and antihistamines (zelastine 0.05%). While almost all patients will require more intensive treatment, these are vital to efficacious treatment. Corticosteroid drops and ointments are commonly employed in the treatment of AKC, especially to achieve control of exacerbations and breakthrough inflammation. Steroid therapy should be tapered as quickly as possible while avoiding rebound inflammation. Calcineurin inhibitors (cyclosporine and tacrolimus) are an effective steroid-sparing therapy. Calcineurin is an enzyme involved in the activation of T cells, a key player in AKC. Tacrolimus is available as a 0.03% and 0.1% topical ointment for dermatologic use (Protopic). It has been used off label for treatment of ophthalmic disease. Topical cyclosporine is available commercially in a 0.05% eye drop preparation (Restasis). Topical calcineurin inhibitors are safe and generally well tolerated, with stinging and eyelid skin maceration being the most common side effect.
Systemic Medications: Systemic antihistamines are routinely used in atopic disease. Oral steroids and cyclosporine are generally reserved for severe/recalcitrant disease or for treatment of dermatologic disease, and are often employed in conjunction with the patient’s dermatologist. Prolonged treatment with oral steroids is avoided due to unacceptable side effects. Systemic cyclosporine, given at dose of 5mg/kg per day has been shown helpful in inducing remission of severe atopic disease. Once remission is obtained, frequency can be decreased to as little as every 5th day. Patients on systemic cyclosporine need regular monitoring of renal function, liver function, blood counts and blood pressure.
Additional Therapy: Zaouali et al reported improvement of symptoms and clinical features of AKC with injection of supratarsal triamcinolone acetonide. Punctal occlusion can useful for concomitant dry eye.
Medical follow up
Patients with AKC require close, long term follow up for development of vision threatening complications and medication side effects such as cataract formation and intraocular pressure elevation.
Amniotic membrane transplantation has been shown to be very effective for persistent corneal epithelial defects.
Tectonic keratoplasty may be necessary for patients with severe corneal thinning or perforations. Penetrating keratoplasty (PK) may be indicated for corneal opacities or severe ulceration/thinning.
Patients with AKC are at increased risk of cataract formation (esp anterior and posterior subcapsular), independent of steroid exposure. Postoperative care and final visual outcomes are impacted by ongoing ocular surface disease.
Eyelid surgery may be necessary for correction of trichiasis, ectropion or entropion.
Surgical Follow Up
PK in AKC patients is associated with higher rate of postoperative complications such as graft rejection, cataracts and glaucoma. Additionally, PK is not curative for AKC; these patients continue to have severe ocular surface disease that can affect viability of the corneal graft. Despite these complications, PK can provide significant improvements in visual acuity. One study looking at long term success of PK in AKC found a 50% failure rate in primary PK, with the primary causes of graft failure being rejection and stromal ulceration.
The clinical presentation of AKC can vary greatly, but in recalcitrant cases, it can cause severe and site threatening corneal complications. Corneal findings range from punctate epithelial erosions to ulcers (infectious or sterile), neovascularization and lipid keratopathy. Herpes simplex keratitis is more common in patients with AKC and often more severe. Patients with AKC are also more likely to get bilateral herpetic disease, which is relatively unusual in the absence of atopy. As with other ocular allergic diseases, patients with AKC are at increased risk of keratoconus due to chronic eye rubbing. Therefore, patients with AKC should be counseled to limit eye rubbing as much as possible, and should be provided with treatment to reduce or eliminate itch. Due to common use of topical and oral corticosteroids, glaucoma is a potential complication of treatment. There are various case reports of conjunctival squamous cell carcinoma in patients with AKC.
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