Ophthalmologic Manifestations of Atopic Dermatitis

Atopy is the hereditary predisposition to allergy or hypersensitivity.[1] Symptoms may present as a dermatitis, hay fever, or asthma.[1] According to Rapoza, Besnier first characterized atopic dermatitis, and many Europeans still use his name to describe the disease (prurigo Besnier).[1] This disease was labeled eczema for many years in the United States until Coca and Cooke coined the term atopy as a skin hypersensitivity seen in patients with hereditary allergies. Wise and Sulzberger have been credited with the term atopic dermatitis to describe a group of diseases associated with atopic conditions that may be seen in all age groups.[2]

Atopic dermatitis (AD) is a chronic and progressive skin disorder that includes an acute stage, characterized by erythema with edema and vesicles, and a chronic stage with skin lichenification.[3]  The SCORAD (Severity Scoring of Atopic Dermatitis) Index characterizes the extent and severity of atopic dermatitis based on surface area involved, intensity of erythema, edema, oozing/crusting, excoriation, lichenification and dryness, as well as subjective symptoms of pruritis and sleep loss.[4]  The purpose of this article is to describe the ophthalmologic complications of atopic dermatitis, specifically keratoconus, atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), bacterial blepharoconjunctivitis, cicatricial entropion, cicatricial ectropion, retinal detachment, cataract and glaucoma.[3]  These ophthalmologic complications can occur with or without other systemic complications including skin infections, gastrointestinal diseases, renal diseases, autoimmune diseases and psychological and psychiatric diseases.[3]

Typical atopic dermatitis on the face of an infant.

Keratoconus (KC) is a non-inflammatory, progressive corneal thinning disorder that leads to corneal protrusion, irregular astigmatism, and corneal scarring in the final stages, that eventually leads to distorted and impaired vision.[3]  The incidence of keratoconus is reported as approximately 0.005% in the general population, but from 0.5% to 39% in those with AD.[3]  One of the symptoms of AD is pruritis, which stimulates eye rubbing, and many studies have demonstrated a link between eye rubbing and keratoconus.[5, 6, 7, 8]  Lastly, there have been reports that individuals with KC are more likely to have atopic tendencies than the healthy control group (35% vs 12%), most commonly allergic rhinitis, but also asthma and AD.[9]

Atopic keratoconjunctivitis (AKC) is a chronic inflammatory allergic disease, with clinical characteristics including conjunctivitis, corneal ulceration, superficial punctate keratitis and corneal neovascularization.[3]

Vernal keratoconjunctivitis (VKC) is typically a self-limiting, atopic disease of the conjunctiva, limbus and/or cornea, with usual onset prior to age 10 years, in individuals with a personal or family history of atopy.[10]

The incidence of bacterial conjunctivitis and blepharitis in AD patients has reportedly been higher than those without AD (86% vs 25%), with S. Aureus identified as the most common pathogen amongst patients with AD (67%).[3] As a result, patients with AD may benefit from pre- and post-operative antibiotic regimens against S. Aureus to prevent infection and its sequelae. 

Cicatricial entropion describes inward turning of the eyelid margin and its appendages secondary to chronic inflammatory changes and subsequent fibrosis, scarring and shortening of the posterior lamellae (e.g. conjunctiva, tarsus), and can lead to lash-cornea touch that may lead to corneal abrasion, scarring, thinning, neovascularization, or even corneal ulceration and perforation in severe cases.[11]

Cicatricial ectropion, in contrast, is caused by shortening of the anterior lamella (i.e. skin and orbicularis muscle), and is also secondary to chronic inflammatory changes including fibrosis and scarring. Similar to other types of ectropion, cicatricial ectropion can lead to exposure keratopathy, corneal abrasion, ulceration, and even thinning and perforation.[12]

Another serious ophthalmologic complication of AD includes retinal detachment, which may be due to eye rubbing as a result of atopic dermatitis-associated pruritis. A review of case studies and another retrospective study[13] , demonstrated that retinal breaks in patients with AD are most likely found in the peripheral fundus, near the ora serrata, which are similar to those caused by trauma (e.g. eye rubbing).[13, 14, 15] Serum IgE levels have not been reported to have an impact on RD.[14]

In patients with AD, cataracts are usually bilateral, symmetric, and occur in the anterior and/or posterior subcapsular regions.[3]  Their progression has been linked to eye rubbing and severity of facial skin lesions, which are likely a sign of increased facial pruritis.[16]  Some articles have not demonstrated a relationship with serum IgE levels, the duration of systemic or facial topical corticosteroid use and cataract development,[14]  whereas other studies have proved an association between high serum IgE levels and cataract development in those with AD.[17]

The relationship with glaucoma and AD is rarely described. Some researchers have denied a correlation between the two conditions,[18]  while Takakuwa et al. have focused on patients with severe AD and advanced glaucoma in order to propose a new clinical entity, "atopic glaucoma", that is thought to arise secondary to increased intraocular inflammatory responses, such as higher IL8 and CCL2 expression in the aqueous humor of these patients.[19]  Takakuwa et al. excluded those cases showing an apparent relation between glucocorticoid use and IOP in order to propose this new clinical diagnosis.[19] These researchers believe that atopic glaucoma is associated with proinflammatory factors, is defined by vertical cup-disc ratio >0.7 and/or neuroretinal rim notching, compatible visual field loss and IOP >21 mmHg.[19]

Atopic dermatitis is primarily caused by cellular immune deficiency and elevated immunoglobulin E (IgE). The pathogenesis can be traced to a genetically inherited, bone marrow–derived cell associated with chromosome 11q.[20] Abnormal skin reactivity also plays a major role in the development of the disease. Irritants to the skin are believed to predispose an individual to develop dermatitis more often than simply exposure to an allergenic trigger.[20] Nonetheless, patients frequently have a history of food or inhalant allergies or eventually develop them.[20]

One of the symptoms of AD is pruritis, which is associated with keratoconus, though the exact mechanism remains unknown. Potential mechanisms of eye rubbing leading to KC include increased corneal temperature, released inflammatory mediators in the tear film and increased enzymatic activity, increased intraocular and hydrostatic tissue pressure, change in keratocytes and a decrease in corneal shear strength.[3]

Frequency

United States

Atopic dermatitis affects approximately 17% of children and 5% of adults in the United States.[21]

Race

No clear racial predisposition appears to exist.[21]

Sex

Males appear to be affected more frequently by AKC and especially VKC than females, though this difference decreases with increasing age.[22]

Age

Children most commonly are affected, with 80% developing the disease before age 7 years. Less than 2% will have an onset after age 20 years. Most sources agree that persistence after age 20 years is uncommon. Only an estimated 10% of patients older than 20 years continue to be symptomatic.[23]

Specific ophthalmologic complications of AD occur at different ages. For example, the peak incidence of AKC is estimated between 30-50 years old, whereas the majority of VKC cases first occur between 10-12 years old.[10, 24]

However, in general, ophthalmologic complications of AD were far more frequent for adults than for children. Specifically, more severe complications leading to ocular morbidity or visual impairment were rare in younger children with mild atopic dermatitis.[25, 26]  

Environmental

The highest incidence of atopic dermatitis is in urban areas. It seems there may be environmental factors in urban areas that predisposes the population to atopic dermatitis as compared to rural settings, but further evaluation of this relationship is needed for the exact cause.[27]  

Specifically, VKC is primarily seen in hot and dry climates, such as West Africa, Middle East, Japan, India and South America, which is though to be secondary to a higher level of pollution by pollens and various other allergens in these areas.[10]

The prognosis is good if the inflammation can be kept under control with therapy.[3] Unfortunately, atopic disease can be controlled but not cured, and management focuses on improvement on symptoms, and prevention of complications and sequelae that can lead to vision loss, while limiting side effects of treatment.[3] Unfortunately, some cases are so severe that treatment will not prevent vision loss and other debilitating complications.

For excellent patient education resources, visit eMedicineHealth's Skin Conditions and Beauty Center. Also, see eMedicineHealth's patient education article Eczema.

Atopic dermatitis is a multifactorial disease with genetic and environmental skin factors.[1, 2] The strongest risk factors are genetic predisposition to poor skin barrier function and dysregulation of the immune system, which also predisposes to other atopic diseases include allergic rhinitis and asthma.[2] In fact, recent studies have implicated loss-of-function mutations in the barrier protein, filaggrin, and diminished expression of certain antimicrobial peptides in those with AD.[1, 2]

Other risk factors that have been proposed include environmental factors such as climate, diet, urban living (proposed to increase pollution exposure), tobacco smoke, and antibiotic use (which can alter the gut microbiome).[2] Lastly, psychological stress has been implicated as a possible contributor to disease development.[2]

As mentioned in the "Overview" section, many of the ophthalmologic manifestations of atopic dermatitis have been associated with frequent and aggressive eye rubbing behavior, which is likely itself secondary to skin irritation and pruritis from AD[21] .

Systemically, the most common symptoms include pruritus, erythema, and skin lesions of the antecubital and/or popliteal skin, eyelids, corners of the mouth, neck, outer canthi, or behind the ears. In infants, the eruption particularly involves the face, scalp, and extensor surfaces. In older children and adults, the neck and antecubital or popliteal areas more commonly are involved. Adult patients usually have a history of infantile disease that may require anecdotal history or contacting their caregivers from infancy. Most patients have a familial occurrence of symptoms of atopy.[2]

As mentioned in the "Overview" section, ophthalmologic manifestations of atopic dermatitis may include pruritic, erythematous lesions of the eyelids, keratoconus, atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), bacterial blepharoconjunctivitis, retinal detachment, cataract and glaucoma.[3]  These complications typically present with vision changes and/or ocular pain and discharge, and ophthalmic physical examination (as below) is necessary to identify the specific complication.

As mentioned in overview, AKC and VKC are more common in boys and VKC is usually seen in younger patients. VKC tends to recur in the spring/summer seasons, whereas AKC is not seasonal.[28]  

The most common physical findings are erythematous, exudative skin lesions of the antecubital and/or popliteal skin, eyelids, corners of the mouth, neck, outer canthi, or behind the ears. Cutaneous scaling, thickening of the skin secondary to irritation and scratching (i.e. lichenification), pigmentary changes including vitiligo and hyperpigmentation (especially in darker skin types), are common in adolescents and adults.[29]  In severe cases, generalized eruptions over the entire body may occur.[29]

More specific physical examination findings of specific ophthalmologic manifestations include:

- Keratoconus: KC is usually bilateral but often asymmetric, and usually presents with slowly progressive irregular astigmatism resulting from paracentral thinning and bulging of the cornea (with maximal thinning near the apex of the protrusion), vertical tension lines in the corneal endothelium (Vogt striae), epithelial iron deposits on the base of the cone (Fleischer ring), an irregular corneal retinoscopic reflex (scissor reflex), and egg-shaped Mires on keratometry. Corneal topography typically shows inferior steepening, and corneal tomography shows posterior elevation.[28] Late-stage KC is characterized by Munson sign (bulging of the lower eyelid when looking downwards) and superficial corneal scarring.[28]  

- Atopic/Vernal Keratoconjunctivitis (AKC and VKC):[30, 31]  Typically bilateral but frequently asymmetric itching with thick, ropy discharge.[28]  

• AKC signs  include eyelid and periorbital skin erythema and thickened dry skin with blistered patches. The tarsal border of the eyelid is thickened (i.e. tylosis) with crusting and scaling, and the meibomian glands are typically dysfunctional. The conjunctiva is typically hyperemic and edematous, with prominent tarsal papillae (i.e. papillary conjunctivitis), which can lead to conjunctival scarring and symblepharon in severe cases. Horner-Trantas dots may be present. The cornea is usually involved, with mild disease including punctate epithelial erosions to ulceration and even perforation, as well as peripheral vascularization and pannus. Anterior and posterior subcapsular cataracts are common. ^[28]  
• VKC signs  include diffuse conjunctival injection and  upper tarsal  giant papillae (giant papillary reaction is more common with VKC than AKC) that can also be near the limbus. Perilimbal Horner-Trantas dots can form, which are focal white limbal dots consisting of degenerated epithelial cells and eosinophils. Like AKC, limbal disease can result in limbal stem cell deficiency which can lead to corneal neovascularization and pannus. Corneal signs related to VKC also include punctate epithelial erosions, which can coalesce into macro-erosions of the corneal epithelium, which in turn can accumulate fibrin and mucous, forming Shield ulcers. Corneal scarring can occur as corneal neovascularization resolves. Lastly, a gray-white lipid can deposit in the peripheral superficial corneal stroma, and is known as pseudogerontoxon. ^[28]  

- Bacterial Blepharoconjunctivitis: Dysregulation in skin barrier allows for much higher infection rate in AD patients than in normal population (67% vs 6% Staphylococcus aureus infection rate).[21]  Physical examination signs include purulent white-yellow discharge, conjunctival papillae, chemosis, and lack of lymphadenopathy.[28]  Cultures typically grow S. aureus (as mentioned in Overview section), but can also grow S. epidermidis, H. influenzae (especially in children, commonly associated with otitis media), Strep pneumoniae, and Moraxella catarrhalis.[28]  

- Cicatricial entropion: describes inward turning of the eyelid margin and its appendages secondary to chronic inflammatory changes and subsequent fibrosis, scarring and shortening of the posterior lamellae, and can lead to lash-cornea touch that results in corneal abrasion, scarring, thinning, neovascularization, or even corneal ulceration and perforation.[11]  Cicatricial entropion is unique from other causes of entropion as it is usually secondary to a systemic inflammatory condition, such as AD, and therefore its definitive treatment should target medical control of the underlying pathologic condition when present.[11]  

- Cicatricial ectropion: is caused by shortening of the anterior lamella, and is also secondary to chronic inflammatory changes including fibrosis and scarring.[12] Similar to other types of ectropion, cicatricial ectropion can lead to exposure keratopathy, corneal abrasion, ulceration, and even thinning and perforation.[12] Like cicatricial entropion, definitive therapy includes treatment of the underlying source of inflammation. 

- Retinal Detachment: AD patients develop retinal detachment in second or third decade of life, and likely to occur bilaterally, likely secondary to retinal tears in the periphery secondary eye rubbing (similar mechanism as ocular trauma).[21]  Exam findings of rhegmatogenous retinal detachments include elevation of the retina from the retinal pigment epithelium by fluid in the subretinal space due to an accompanying full-thickness retinal break(s), with or without anterior vitreous pigmented cells (ie, Shafer sign).[28]  A mild relative afferent pupillary defect may be present.[28]  

- Cataracts: Cataracts associated with AD are typically anterior and/or posterior subcapsular cataracts, and are distinct from the nuclear and cortical cataracts common in the general population.[21]  These cataracts usually develop in patients with long-standing atopic disease (ie, 10 or more years). These cataracts are typically bilateral and tend to evolve rapidly, with opacification within 6 months. The cataracts often begin as a posterior subcapsular opacity and develop into an anterior subcapsular opacity that frequently resembles the shape of a shield.[32]

- Atopic glaucoma: Exam findings of "atopic glaucoma" have been proposed by Takakuwa et al. as vertical cup-disc ratio > 0.7 and/or notching of the neuroretinal rim with compatible visual field loss, intraocular pressure > 21 mmHg, with the presence of severe atopic dermatitis as defined by the Japanese Dermatological Society (i.e. rash affects face, rash involves 10-30% of body surface area in severe AD, and >30% of the body surface area in very severe AD).[19]  These researchers obtained aqueous humor samples to assess for inflammatory cytokine expression, but excluded patients on glucocorticoids, and also excluded any case that showed an apparent relation between glucocorticoid usage and IOP, in order to propose "atopic glaucoma" as a unique clinical diagnosis associated with intraocular inflammation secondary to severe or very severe AD.[19]

- Herpetic Eye Disease: AD patients have a four-fold increased risk of developing ocular Herpes Simplex Virus (HSV).[21]  Physical exam findings related to herpetic eye disease differ on the location and severity of disease, and may involve the eyelid/skin (i.e. clear vesicles on an erythematous base that progress to crusting), conjunctivitis (i.e. conjunctival injection with ipsilateral follicular conjunctivitis, with or without conjunctival dendrites or geographic ulceration), corneal epithelial disease (ie, dendritic keratitis, geographic ulcer, corneal desensitivity, subepithelial scars and haze in the healing stages, neurotrophic ulceration, disciform keratitis, necrotizing interstitial keratitis, herpetic uveitis, herpetic retinitis).[28]

Diagnosis of AD and its associated ophthalmologic complications are clinical diagnoses based on history and physical exam findings (with details in the "Presentation" tab). A family history of atopic disease (including asthma, allergic rhinitis and/or AD) is usually present.[33] Laboratory studies, cultures and histopathologic analyses to aid in diagnosis are described below. 

Laboratory tests that may aid in diagnosis of AD and its ophthalmologic manifestations, especially in the early clinical stages, include various types of skin testing and serum testing for elevated immunoglobulin E (IgE). IgE levels in tears have also been shown to correlate with clinical severity of atopic eye disease including AKC.[1, 2, 33]

Patients with atopic dermatitis display immediate skin test reactivity and may display skin blanching to cholinergic agents.[2]

Culture of eyes with conjunctivitis associated with atopic dermatitis usually grows Staphylococcus aureus. Brush cytology, a process that involves taking superficial scrapings from the tarsal conjunctiva, has been used to quantify levels of inflammatory cells, including eosinophils and neutrophils, and has been correlated to disease severity.[2, 33]

Once a clinical diagnosis of atopic dermatitis has been established, lab testing is generally unnecessary.[2]

Skin and conjunctival biopsy is rarely used to diagnose AD and ophthalmologic complications including AKC. Examination of histopathologic sections early in the disease process show parakeratosis, hyperkeratosis, acanthosis, intercellular and intracellular fluid accumulation, and perivascular infiltration of the dermis and epidermis by lymphocytes, monocytes, and macrophages.[34] Later in the disease, observation reveals hyperkeratosis, dyskeratosis, acanthosis, and a thickened epidermis.[34] Lysosomes have been demonstrated by electron microscopy.[34] Conjunctival biopsy shows mast cell and inflammatory cell (eg, eosinophils and neutrophils) infiltration of the conjunctival epithelium.[3, 33]

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 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]

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]

Patients with known atopic disease may have various food allergies that trigger or exacerbate their disease. Avoidance of these foods is essential.[35]

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]

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]

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.

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.

The SCORAD (Severity Scoring of Atopic Dermatitis) Index, published in 1993 in Dermatology, characterizes the extent and severity of atopic dermatitis based on surface area involved, intensity of erythema, edema, oozing/crusting, excoriation, lichenification and dryness, as well as subjective symptoms of pruritis and sleep loss.[4] This scoring system shows a normal distribution of the population studied, and uses a mathematical weighing system of the signs/symptoms, such that extent and subjective symptoms account for about 20%, whereas intensity items represent 60%, of the total score.[4]

The most commonly used treatment strategies include antibiotics, corticosteroids, antihistamines, and less commonly, immunomodulating therapy, UV light, and hospitalization (rare).[35] For most cases of atopic dermatitis (without AKC), application of topical steroids to the affected area is usually sufficient. Ocular involvement may be managed with topical mast cell stabilizers, topical calcineurin inhibitors (e.g. Restasis or Verkazia), topical steroids, or if symptoms persist, oral antihistamines (e.g. over-the-counter diphenhydramine) and oral steroids.[33] AKC may require all of these, and some ophthalmologists recommend that an oral antibiotic be given in addition to a topical antibiotic for the affected eye(s).[33] Antibiotic treatment should target S. aureus, the most likely pathogen, and should be chosen based on the patient's allergies and cultures.[33] Immunomodulatory therapy will only very rarely be required, and these will unlikely be prescribed by the ophthalmologist.[35]

Fore more detailed discussion on medical treatment, please see the "Treatment" section.

Class Summary

As anti-inflammatory and immunosuppressive agents, corticosteroids are beneficial in treating atopic dermatitis. Dexamethasone, fluorometholone, hydrocortisone, and prednisolone are the most commonly available preparations of ophthalmic steroids in the United States. Preparations range from 0.05-2.5%. For most topical purposes, a 0.5% preparation of prednisolone, cortisone, or hydrocortisone is adequate.

Prednisolone ophthalmic (Omnipred, Pred Forte, Pred MIld)

Based on 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.

Fluorometholone (Flarex, FML, FML Forte, FML Liquifilm)

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.

Class Summary

May be useful as prophylaxis against exacerbation of the disease.

Lodoxamide (Alomide)

Inhibits degranulation of mast cells and helps prevent histamine release.

Cromolyn

Inhibits histamine and slow-releasing substance of anaphylaxis (SRS-A) release from mast cells but has no intrinsic anti-inflammatory, antihistamine, or vasoconstrictive effects.

Nedocromil ophthalmic (Alocril)

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

Class Summary

Useful in decreasing itching and scratching associated with atopic dermatitis.

Hydroxyzine (Vistaril)

Antagonizes H1 receptors in periphery; may suppress histamine activity in subcortical region of CNS; may assist in sleep.

Diphenhydramine (Benadryl, Benadryl Dye-Free Allergy, Complete Allergy Relief, Q-Dryl, Diphen)

Diphenhydramine is for symptomatic relief of urticaria symptoms caused by the release of histamine in allergic reactions.

Loratadine (Alavert, Allergy Relief, Claritin, Loratadamed)

Loratadine selectively inhibits peripheral histamine H1 receptors.

Desloratadine (Clarinex)

Desloratadine is a long-acting tricyclic histamine antagonist that is selective for H1 receptors. This agent is a major metabolite of loratadine, which, after ingestion, is extensively metabolized to active metabolite 3-hydroxydesloratadine.

Fexofenadine (Allegra Allergy, Allegra Allergy 24 Hour, Mucinex Allergy)

Fexofenadine competes with histamine for H1 receptors in the GI tract, blood vessels, and the respiratory tract, reducing hypersensitivity reactions.

Class Summary

Atopic conjunctivitis requires the use of topical antibiotics that particularly target S aureus, the most common pathogen. Since most ophthalmic antibiotics will target this bacterium, physician discretion, reference to package inserts, and the ophthalmic Physicians' Desk Reference are recommended. Patients' allergies and compliance should be considered.

Gatifloxacin ophthalmic (Zymaxid)

Fluoroquinolone with activity against streptococci, staphylococci, Corynebacterium propinquum, and Haemophilus influenzae; inhibits bacterial DNA synthesis and, consequently, growth.

Class Summary

Inhibit calcineurin, an enzyme involved in T cell activation, thereby decreasing the level of inflammatory cells and mediators on the ocular surface.

Restasis (cyclosporine ophthalmic emulsion, 0.05%)

Restasis is available in single-use or multidose vials, and is commonly used in the treatment of:

1) VKC:1 drop four times a day, treatment can be discontinued once signs/symptoms have resolved and can be restarted once signs/symptoms recur

2) Keratoconjunctivitis sicca: therapeutic by increasing tear production, 1 drop twice daily 

3) Corneal melting syndromes of known or presumed immunologic etiology, e.g. Mooren's ulcer

4) Prevention of graft rejection, in high risk patients, especially after penetrating keratoplasty

5) Keratoconjunctivitis: useful adjunctive treatment in cases of HSV stromal keratitis

Verkazia (cyclosporine ophthalmic emulsion, 0.1%)

FDA approved in June 2021 for the treatment of VKC in children and adults. Verkazia was studied in two randomized, multicenter, double-masked, vehicle-controlled clinical trials: the VEKTIS study and NOVATIVE study, and showed improvement in corneal inflammation and ocular itching in both studies. The most common adverse reactions (>5% of patients) included (usually) transient eye pain and pruritis. Verkazia can be started and stopped as signs/symptoms of VKC have started and have resolved, respectively.