Approach Considerations
Treatment of AD and its ophthalmologic complications, including AKC and VKC, includes improvement of symptoms, limiting exacerbations and preventing complications and sequelae that leads to vision loss, all while limiting side effects of treatment. [35] The multifactorial nature of the disease means that its manifestations should be managed by a multifactorial team of specialists, including ophthalmologists, dermatologists and allergists. [35]
Management includes limiting psychosocial stress, avoidance of allergens (most commonly dust mites, peanuts, egg, milk, fish, rice, soy, and wheat), and irritants (particularly chemicals, soaps, heat, humidity, wool, and acrylic), which can be obtained by use of hypoallergenic bedding, avoidance of pets, use of filtering devices, and dietary changes as appropriate. [35, 33]
Medical Care
Medical therapy for AD depends on disease extent and severity. Mild disease can be treated with hand hygiene, cold compresses, antihistamines (eg, zelastine 0.05%) and mast cell stabilizers (eg, olapatadine 0.1% or iodoxamide 0.1%). Moderate disease is typically treated with topical corticosteroids. [33] Steroid therapy should be tapered as quickly as possible though slow enough to prevent rebound inflammation. Topical calcineurin inhibitors, including cyclosporine and tacrolimus, can be used as steroid-sparing therapy, and work by inhibiting calcineurin, an enzyme involved in activation of T cells. [33] Topical tacrolimus is available in 0.03% and 0.1% ointments, and has been approved for dermatologic use, though it is often used off-label for treatment of ophthalmic disease including AKC and VKC. Topical cyclosporine is available commercially as 0.05% eye drop preparation (i.e. Restasis), and recently as a preservative-free 0.1% emulsion (Verkazia), which has very recently been approved by the FDA for treatment of VKC in children and adults. [36] Both Restasis and Verkazia are generally well tolerated, with the most common side effects being local ocular burning and pruritis, both of which were usually transient. [33] Medical temporizing measures for treatment of cicatricial ectropion include ocular surface lubrication and horizontal taping of the eyelid. [12] Severe and recalcitrant disease can be treated with oral corticosteroids, systemic cyclosporine, and/or supratarsal triamcinolone (in the case of AKC and VKC). [37]
Systemic antihistamines are used often for atopic disease. [33] Oral steroids and cyclosporine are generally reserved for severe/recalcitrant ophthalmologic and/or dermatologic disease, and are often managed with a dermatologist. Prolonged steroid use is avoided given the side effects, and instead, systemic cyclosporine (at 5 mg/kg per day) has been used to induce remission of severe atopic disease. [33] Once remission is obtained, oral cyclosporine dose frequency is decreased. [33] Patients on long-term systemic cyclosporine need monitoring of renal and hepatic function, as well as blood counts and blood pressure. [33]
In addition to the treatment above, IOP-lowering drops can be used in the medical management of atopic glaucoma. [19]
Consultations
Ophthalmology consultation is recommended if eye involvement is noted. Dermatology consultation, in coordination with allergist, may be necessary to further evaluate and manage AD and its complications. [38]
Diet
Patients with known atopic disease may have various food allergies that trigger or exacerbate their disease. Avoidance of these foods is essential. [35]
Surgical Care
Of course, specific surgical therapy is warranted for specific ophthalmologic manifestations of AD, including but not limited to: amniotic membrane transplantation, tectonic or penetrating keratoplasty (as below), eyelid surgeries for cicatricial entropion or ectropion (described in more detail below), filtering surgery for atopic glaucoma, vitrectomy and endolaser for retinal detachment, and cataract surgery.
For AKC and VKC, amniotic membrane transplantation has been shown to be very effective for persistent corneal epithelial defects. [33] Severe corneal ulceration, thinning and perforation may necessitate tectonic or penetrating keratoplasty. [33]
Eyelid surgery may also be necessary for treatment of cicatricial entropion, trichiasis, and cicatricial ectropion. [33] Specifically, cicatricial entropion management differs depending on entropion severity. In mild disease, options include: skin resection alone to the eyelid margin outwards, lash follicle excision or cauterization. In moderate disease, transverse blepharotomy and marginal rotation of the upper or lower eyelids, or tarsal fracture with everting sutures for the upper eyelid can be used. For severe cicatricial disease, scar tissue and lid retractors are released, and then the posterior lamella are lengthened using grafts such as hard palate graft, other mucous membrane graft, or allograft. [11] The most common complication following cicatricial entropion repair is recurrence, which can be minimized by mild overcorrection at the time of repair. [11] Surgical therapy for cicatricial ectropion includes lengthening of the anterior lamella with a skin graft. [12]
The medical and surgical treatments above are more likely useful in AKC than VKC, given that VKC is generally a self-limiting disease that resolves with age or spontaneously at puberty. [10]
Complications
Corticosteroids
Corticosteroids are associated with many potential ocular and systemic complications, specifically cataract formation, glaucoma development, and corneal thinning. [39] These side effects must be weighed against the therapeutic benefit of steroid therapy, and consideration should be given to steroid-sparing agents as above. [39]
Long-term use of steroids, especially systemically, should be avoided given the large side effect profile.
Dupilumab
Dupilumab is a human monoclonal antibody directed against the shared α subunit of the interleukin (IL)-4 and IL-13 receptor, and has been approved for adolescent and adult patients for AD. [40]
More recent clinical trials of dupilumab showed a higher incidence of conjunctivitis in dupilumab-treated patients compared to the placebo group. [41] Upregulation of Th1-mediated inflammation has been proposed as a mechanism for dupilumab-induced conjunctivitis, though more research is needed in this area. [42]
Prevention
Stress control, avoidance of allergen (most commonly dust mites, peanuts, egg, milk, fish, rice, soy, and wheat), and irritants (particularly chemicals, soaps, heat, humidity, wool, and acrylic) may help control the disease.
Long-Term Monitoring
Besides regular follow-up with a multidisciplinary team including ophthalmologists, dermatologists and allergists, skin scratching and eye rubbing should be minimized and avoided if possible.
Scratching the cutaneous lesions can worsen them and lead to the lichenification process characteristic of long-standing disease.
Eye rubbing is associated with many of the ophthalmologic manifestations of AD (as noted in detail above). Antihistamines, mast-cell stabilizers, and corticosteroids may help in controlling the irritation and pruritis, and therefore prevent or at least minimize eye rubbing.
Nails should be kept clean and trimmed to minimize infection or superinfection if cutaneous lesions are scratched.
In pediatric patients, mittens may be used at night or even during the day, when possible, if pruritis and scratching are severe.
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Typical atopic dermatitis on the face of an infant.
