VKC is characterized by intense ocular itching exacerbated by exposure to wind, dust, bright light, hot weather, or sweating. Tearing, mucous discharge, conjunctival hyperemia, photophobia, blepharospasm, eye pain, foreign body sensation, and sometimes ptosis may be seen.

There are two forms of the disease: limbal or palpebral, depending on which portion of the conjunctiva is predominantly affected. Clinical examination may reveal a thin, copious milk-white fibrinous secretion (composed of epithelial cells, eosinophils and Charcot–Leyden crystals). Palpebral involvement may include conjunctival hyperemia and edema with papillae (filled with inflammatory cells) on the superior tarsal conjunctiva (Fig. 4.2). Giant papillae are seen as the disease progresses due to fibrous tissue proliferation and can reach 7–8 mm in diameter (so-called “cobblestone” papillae). Fibrin may accumulate on the giant papillae and is known as the Maxwell-Lyons sign. VKC patients can also show Dennie Morgan’s line. Persistent forms of VKC are associated with subepithelial fibrosis that appears as a white linear scar running parallel to the lid margin (Arlt’s line). Limbal involvement includes transient confluent gelatinous limbal papillae and clumps of necrotic eosinophils with dead epithelial cells and neutrophils on the limbus or conjunctiva seen as yellow-white points (Horner’s points and Trantas dots) and conjunctival hyperemia with edema (Figs. 4.3 and 4.4) (Kumar 2009). Trantas dots tend to appear when VKC is active, and disappear when symptoms decrease (Friedlaender 2011), while the cobblestones persist even during quiescent phases of the disease. Corneal involvement is associated with more severe disease. Corneal epithelial punctate keratitis (called keratitis epithelialis vernalis of El Tobgy) may evolve to macroerosion, ulcers and plaques, which are all expressions of epithelial toxicity caused by factors released from activated eosinophils (Leonardi et al. 2008). The classic corneal change seen more commonly in patients with superior tarsal involvement, is the development of a noninfectious shield ulcer appearing as an irregular oval corneal plaque with elevated hypertrophic epithelial cells with fibrin and mucin that stains with fluorescein and contains eosinophils and epithelial cells (Fig. 4.5) (Udell et al. 1981; Abelson and Granet 2006). Superficial corneal neovascularization and sometimes filamentary keratitis may also occur (Zicari et al. 2013).

Although VKC is a bilateral disease, it may affect one eye more than the other.

Ocular complications of VKC include steroid-induced cataract, glaucoma and dry eye, corneal scarring, irregular astigmatism, microbial keratitis, limbal tissue hyperplasia, and keratoconus (Tabbara 1999; Sridhar et al. 2003). Amblyopia seen among VKC may be caused by corneal opacity, irregular astigmatism, and keratoconus (Kumar 2009). A common corneal degenerative change is pseudogerontoxon, in which there is increased lipid deposition in the peripheral portion of the cornea resembling corneal arcus senilis (Fig. 4.4).

No precise diagnostic criteria have been established for this disease. Diagnosis is based on typical and characteristic clinical signs and symptoms; thus many mild or atypical cases may escape diagnosis. The diagnosis is based on the classical symptoms of allergic conjunctivitis (itching, tearing and hyperemia), and on specific ocular signs such as proliferative lesions in the conjunctiva including giant cobblestone papillae on the upper palpebral conjunctiva, limbal proliferation with limbal gelatinous hyperplasia and Horner–Trantas dots (Fig. 4.3) and the corneal findings described above. Even though atopy is common among VKC patients, only 50% of patients with VKC has positive Skin Prick Test and/or elevated allergen-specific antibodies (Pucci et al. 2003; Bonini 2004). Increased total IgE antibodies in serum and lacrimal fluid eosinophils in the conjunctival smear are common findings.

Ocular symptoms result from a nonspecific hyperreactivity induced by nonspecific stimuli, such as wind, dust, and sunlight, which is not related to allergen levels in the environment (La Rosa et al. 2013). Immunological data has proved that the pathogenesis of VKC is a type 1 and a type 4 hypersensitivity reaction. Recently, many authors have suggested the existence of a cooperation between the allergic (Th2 mediated) and the inflammatory (Th1 mediated) responses (Leonardi et al. 2006; Zicari et al. 2013). The immunopathogenesis of VKC is multifactorial involving a Th2 mediated mechanism with an overexpression of Th2-derived cytokines, growth factors, mast cells, eosinophils, neutrophils, lymphocytes, and corneal fibroblasts that perpetuate the ocular allergic inflammation (Leonardi et al. 1999; Trocme and Sra 2002; Kumagai et al. 2006). In VKC, antigen presenting cells, such as Langerhan’s cells, are associated with co-stimulatory molecules (CD86) that provide an important mechanism for Th2 cell activation (by interacting with CD28) and further cytokine release (Abu-El-Asrar et al. 2001a).

In the type 1 hypersensitivity reaction, ligands expressed in conjunctival B cells such as CD23, CD21, and CD40 are crucial for the interactions in the production of IgE (Abu-El-Asrar et al. 2001b). The tears of VKC patients contain high levels of IgE, histamine and mast cell mediators, including major basic protein (MBP), eosinophil cationic protein (ECP), Charcot–Leyden crystals, basophils, IgE- and IgG-specific for aeroallergens (e.g., ragweed pollen) and eosinophils (Ballow and Mendelson 1980; Irani et al. 1990; Bielory 2000).

Chemokines such as IL-4 and IL-13 are involved in the formation of giant papillae by inducing the production of extracellular matrix and the proliferation of conjunctival fibroblasts (Leonardi et al. 2007). IL-8 in the extracellular space of the conjunctival epithelium plays an important role in the recruitment of neutrophils and eosinophils and in the pathogenesis of corneal damage in severe allergic diseases (Miyoshi et al. 2001). Degranulated eosinophils and their toxic enzymes such as ECP and MBP have been found in the tears and conjunctiva as well as in the periphery of corneal ulcers, suggesting their etiopathogenic role in many of the problems associated with VKC (Bielory 2000).

The increased conjunctival infiltration with eosinophils, basophils, mast cells, plasma cells, lymphocytes, macrophages, and fibroblasts, when compared to seasonal and perennial allergic conjunctivitis, may contribute to the serious complications seen in VKC (Trocme and Sra 2002). Granules with cytotoxic mediators are secreted by eosinophils releasing major basic protein, eosinophil cationic protein, eosinophil peroxidase, and gelatinase B which damage corneal epithelium and affect wound healing (Trocmé et al. 1993, 1997; Abu-El-Asrar et al. 2001c). Enzymatic degradation of histamine has been shown to be significantly lower in patients with VKC compared with normal patients in both tears and plasma, suggesting that this dysfunction may be a primary factor in the pathophysiology of VKC (Abelson et al. 1995).

Primary interventions, such as environmental modification and minimizing or avoiding the offending allergens as much as possible, are an important first step for all types of allergic conjunctivitis. For the more common allergens, simple measures including installing high-efficiency air filters and air conditioning, meticulous removal of dust such as vacuum cleaners with special filters, removal of drapes and carpets, protective goggles, sealing bedding, washing linens in hot water, avoidance of pets or keeping pets out of the sleeping areas and washing the child’s hair in the evening prior to sleeping, can keep the allergen away from the eyes and the upper respiratory system. Some of these recommendations, especially involving beloved pets, can be difficult to implement. Cold compresses may aid in symptom relief, especially ocular pruritus. Eye lubricants, ideally preservative-free artificial tears, provide a barrier function and help to improve the first-line defense at the level of the conjunctival mucosa, helping to wash out or dilute allergens and inflammatory mediators of the ocular surface. Ointments are commonly used at night and provide moisture to the ocular surface while the child sleeps. Although frequently unsuccessful, discouraging of rubbing the itchy eyes is important.