Atopic Keratoconjunctivitis
Introduction
Within the spectrum of allergic eye diseases, atopic keratoconjunctivitis (AKC), along with perennial allergic conjunctivitis (PAC) (Ch. 13), vernal keratoconjunctivitis (VKC) (Ch. 14) and, to a certain extent, giant papillary conjunctivitis (GPC) (Ch. 16), is categorized as a form of chronic allergic conjunctivitis (CAC). Along with the milder, more acute seasonal allergic conjunctivitis (SAC) (Ch. 13), these conditions characteristically involve an IgE-mediated type I hypersensitivity response, manifested by papillary conjunctivitis, with itching as a universal early symptom. However, the more chronic AKC, along with VKC, is distinguished from seasonal and perennial allergic conjunctivitis, by the complex recruitment of other immunologic mechanisms, including a prominent T-cell-mediated type IV hypersensitivity response, as well as a variety of other inflammatory cell types and cytokines. The potential for corneal involvement and opacification increases significantly with the CACs because of the severity and sustained nature of their inflammation. The highest incidence of visual loss is therefore, found in the most chronic of these disorders, AKC.
Definition and Associated Risk Factors
Atopic keratoconjunctivitis (AKC) was first described in 1952 by Hogan, who described five cases of atopic eczema associated with bilateral keratoconjunctivitis.1 He recognized an association between the skin and eye findings, coining the term ‘atopic keratoconjunctivitis.’ His patients were notable for chronic conjunctival hyperemia and thickening, corneal epitheliopathy, and later corneal scarring and neovascularization. Based on his observations, he outlined several criteria to aid in diagnosing this unique condition: the presence or history of eczematous dermatitis, a family history of atopic disease, associated allergies (asthma, hay fever), eosinophilia, and a characteristic keratoconjunctivitis associated with exacerbations of the dermatitis.
Few studies have established the incidence of AKC. However, atopic dermatitis (AD), its most frequent extraocular association, has been estimated to affect between 5% and 20% of the general population, making it the most common chronic inflammatory condition of the skin. The incidence of AD is greatest in the pediatric population Twenty-five to forty-two percent of AD patients are found to have ocular involvement.2,3 AKC may occur at any time after the onset of the associated dermatitis or other atopic condition, and is not necessarily correlated with exacerbations of these conditions.4 The initial presentation of ocular symptoms in AKC most commonly occurs in the second to third decade of life, with some patients presenting earlier or later. Visually significant complications most frequently occur in the fourth to fifth decades, with more men affected than women. The condition then remains chronic for years, usually requiring lifelong treatment. Studies suggest that an earlier onset of AKC, for example in childhood, carries the greatest risk for tear film abnormalities and greater ocular surface damage.5 A survey of CAC in a referral practice found that AKC and VKC were equally observed (39% each), while 13% were diagnosed with PAC.6 However, the chronicity and visual complications of AKC would be expected to skew this population, causing AKC to be over-represented in referral practice, when compared to the general population.
As suggested by Hogan, the strong association between AKC and eczematous dermatitis cannot be overemphasized, with at least 95% of AKC cases presenting in patients with some history of this chronic skin condition.7 Other atopic conditions associated with AKC include asthma and allergic rhinitis, each seen in 65–87% of AKC patients.8 Although a handful of case reports have described AKC without other atopic disease, later investigation will usually reveal some form of systemic atopy. Patients will also frequently describe a family history of atopy. Recently, Guglielmetti et al. have suggested that Hogan’s definition be modified to include the clinical features described below, combined with the presence of any atopic condition (e.g. atopic dermatitis, periocular eczema, asthma), occurring at any time point during the atopy, independent of its severity, and exhibiting corneal involvement at some point in the course of disease.4
Clinical Presentation
Eyelids
The periorbital skin and eyelids display a scaling, flaky dermatitis consistent with eczema (Fig. 15.1). There may be periorbital hyperpigmentation, which may lighten in response to control of the inflammation. In long-standing AKC, de Hertoghe sign, or absence of the lateral brow, is occasionally seen and may also be related to chronic eye rubbing. Vertical corrugations near the medial canthus of the upper and lower eyelid may also result. The eyelid margins may be thickened, edematous, and hyperemic. Eyelid edema may lead to Dennie–Morgan lines, single or double creases in the lower eyelid. The eyelid skin is often fissured, and lateral canthal ulceration related to chronic tearing may be present (Fig. 15.2). Lid malposition (usually ectropion), ptosis, lagophthalmos and madarosis may all result from chronic eyelid edema and inflammation. The chronic edema can lead to permanent lid swelling, a hallmark of long-standing atopic eye disease. Keratinization of the eyelid margins is sometimes observed, along with associated meibomianitis and obliteration of meibomian glands.
Conjunctiva
The palpebral conjunctiva reveals papillary hypertrophy, more prominent on the lower tarsus. There may be giant papillae as in VKC (Fig. 15.3). Diffuse sheet-like infiltration of the conjunctiva may lead to pale white edema and obscuration of blood vessels (Fig. 15.4). Conjunctival scarring may occur, often in a reticular or septal pattern (Fig. 15.5). Subepithelial fibrosis can, in severe cases, lead to symblephara, inferior forniceal foreshortening, and cicatricial ectropion. The bulbar conjunctiva typically displays diffuse chemosis and injection. The limbus may become infiltrated and edematous, and gelatinous limbal hyperplasia, consisting of confluent macropapillae, is sometimes seen. Trantas dots, tiny white lesions consisting of necrotic epithelial cells and eosinophils, may be observed, similar to those in VKC (Fig. 15.6).
Figure 15.6 Trantas dots and pannus of the superior cornea.
Cornea
Corneal disease may be complicated by the late development of corneal hypesthesia in patients with AKC, resulting in a paradoxic reduction in surface symptoms, including itching. Punctate epithelial keratopathy is the most common corneal finding. Filamentary keratitis may occur, sometimes with very thick mucoid filamentary strands and possibly related to tear film instability, due to goblet cell abnormalities and deficient mucin secretion, also commonly featured in AKC. Persistent epithelial defects frequently occur in the setting of a dry and inflamed ocular surface and may eventually lead to macroerosions (Fig. 15.7). These pose a particular problem in the atopic patient and can progress to frank bacterial ulcers. Atopic shield ulcers with ‘vernal’ plaque formation may also develop. Histologically, these adherent mucus plaques contain epithelial debris, eosinophils, and inflammatory cells, and probably result from a combination of mechanical irritation from giant papillae, as well as toxic epithelial changes secondary to inflammation. Persistence of these plaques may eventually cause stromal thinning and perforation (Fig. 15.8). The chronic inflammation and mechanical insult from palpebral scarring may eventually result in partial or total limbal stem cell deficiency (Fig. 15.9). Chronic inflammation and superimposed infection may lead to corneal scarring, neovascularization, and lipid deposition. Severe pannus often develops, typically affecting the superior one-third of the cornea. Vision may decline due to obscuration of the visual axis, irregular astigmatism, and/or ocular surface compromise. A pseudogerontoxon may be seen in the peripheral cornea, which resembles a short, circumferential segment of arcus senilis. This localized area of lipid deposition, related to abnormal vascular permeability at the limbus, may be the only evidence of previous atopic disease in a quiet eye.9
Other complications
Eyelid inflammation is common in AKC, often related to staphylococcal blepharitis. In fact, patients with atopic dermatitis are found to have high rates of bacterial skin colonization, specifically with staphylococcal species. AKC patients are at higher risk of corneal superinfections because of an unstable ocular surface, the local bacterial colonization of the eyelids, and a dysfunctional innate immune system.10 Herpes simplex keratitis, frequently bilateral, is another well-known complication of AKC, and is presumably related to abnormalities in the atopic host’s immune defenses (Fig. 15.10). Herpetic epithelial lesions may be recurrent, especially when topical or systemic immunosuppressants are required to control the atopic state.11 Management is especially difficult because epithelial AKC lesions may be difficult to distinguish from HSV keratitis.
Rapidly progressive cataracts frequently develop in AKC patients, classically described as anterior subcapsular opacities, usually stellate or shield-like in appearance. The pathogenesis for atopic cataract is unclear, though some have suggested that high levels of IgE may be correlated with development of cataract in these patients.12 The chronic use of topical steroids also predisposes to posterior subcapsular cataracts in AKC patients. Other forms of cataract may form independent of corticosteroid use, especially in patients with severe systemic atopic disease.
A higher incidence of keratoconus and pellucid marginal degeneration has been reported in AKC patients, likely related in part to chronic eye rubbing (Fig. 15.11).3,13 Interestingly, a slightly higher rate of retinal detachment has also been noted in AKC patients. This may also be related to chronic eye rubbing, inducing degenerative vitreous changes.14
Figure 15.11 Contralateral eye from patient depicted in Figure 15.10, showing keratoconus on corneal topography.
Power and colleagues reported on the frequency of different clinical features in AKC, based on long-term follow-up (average, 7 years) of a cohort of 20 AKC patients.8 In their series, all 20 patients had eczema, and half had a family member affected with atopy. All patients had conjunctival hyperemia, and 65% had papillary reaction. Roughly half displayed some form of conjunctival scarring, including subepithelial fibrosis, forniceal foreshortening and symblepharon formation. All patients had superficial punctate keratitis. Fourteen of the 20 patients had severe corneal complications, including persistent epithelial defect (seen in half of the patients), corneal ulceration, or bacterial keratitis. Three patients developed herpetic keratitis. Two had keratoconus. Seven patients (nine eyes) required penetrating keratoplasty, some for corneal perforation.
