Vernal Keratoconjunctivitis

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Article initiated by:

Jordan Scott Masters, MD

All contributors:

Jordan Scott Masters, MD, Vatinee Y. Bunya, MD, MSCE, Maria A. Woodward, MD, Koushik Tripathy, MD (AIIMS), Colleen Halfpenny, M.D.

Assigned editor:

Colleen Halfpenny, M.D.

Review:

Assigned status Update Pending

 by Colleen Halfpenny, M.D. on January 11, 2025.

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Vernal Keratoconjunctivitis

Vernal Keratoconjunctivitis © 2017 American Academy of Ophthalmology

DiseasesDB

30842

ICD-10

H16.2

ICD-9

370.32

Vernal keratoconjunctivitis (VKC) is an atopic condition of the external ocular surface. It characteristically affects young males in hot dry climates in a seasonal manner; however this is not always the rule.

Disease Entity

• ICD-9 370.32
• ICD-10 H16.263 

Disease History

The first description of VKC is credited to Arlt who described 3 cases of perilimbal swelling in young patients in 1846. In 1899, Trantas described the limbal white dots that had been previously demonstrated by Horner. In 1908, Gabrielides identified eosinophils in conjunctival secretions as well of the peripheral blood of VKC patients. In 1910, Trantas characterized the spectrum of corneal changes seen in VKC.

Demographics and Epidemiology

VKC is a condition seen primarily in hot and dry climates most commonly in West Africa and the Mediterranean basin. It is also seen commonly in the Middle East, Japan, India, and South America. It is thought to be relatively unusual in North America and Western Europe. The increased incidence in hot regions is speculated to be secondary to a higher level of pollution by pollens and various other allergens. Males are affected more than females, but this difference becomes smaller as age increases. It is difficult to obtain an accurate prevalence, because many patients may not present to clinics if they may have a mild form of the disease and the condition is largely self-limiting. Depending on region and climate, prevalence of VKC can vary widely. Additionally, prevalence in endemic regions is much higher when comparing adolescents to the population as a whole. For instance, 1 European study demonstrated that the prevalence was between 1.2 and10.6/10,000. At least 1 study exhibited a 4% prevalence in African schoolchildren. The majority of VKC occurs in patients between the ages of 5 and 25 years, with an age of onset between ages 10 and 12 years; however, there are reports of patients as young as 5 months old.

Pathophysiology

A personal or family history of atopy is seen in a large proportion of VKC patients. VKC was originally thought to be due to a solely IgE mediate reaction via mast cell release. It has now been shown that IgE is not enough to cause the varied inflammatory response that is seen with VKC. Activated eosinophils are thought to play a significant role and they can be shown consistently in conjunctival scrapings; however, mononuclear cells and neutrophils are also seen. Additional attention has been given to the CD4 T-helper-2-driven type IV hypersensitivity with immunomodulators such as IL-4, IL-5, and bFGF. Thought has been given to a possible endocrine method as well, because there is a decrease in symptoms and prevalence after puberty.

A hereditary association has been suggested, but no direct genetic associations have been made. VKC is seen more often in patients who have atopic family histories, but no clear correlation with specific genetic loci has been elucidated.

Diagnosis

Symptoms

VKC is characterized by symptoms consisting of severe itching, photophobia, foreign body sensation, mucous discharge (often described as “ropy” or string-like), blepharospasm, and blurring of vision. In a 1988 review, Buckley coined the term “morning misery,” which described the active disease state of patients with severe discomfort, blepharospasm, and mucous discharge leaving them incapacitated upon awakening and “frequently resulting in lateness for school.” It is typically bilateral but may be asymmetric in nature. While VKC is typically seasonally recurrent ("vernal" refers to springtime; another name for VKC is "spring catarrh"), 23% of patients may have a perennial form of the disease, and many may have recurrences outside of springtime.

Signs

The signs of VKC can be divided into conjunctival, limbal, and corneal signs.

• Conjunctival signs include diffuse conjunctival injection and upper tarsal giant papillae. These are discrete papillae measuring >1 mm in diameter. They characteristically have flattened tops that sometimes demonstrate stain with fluorescein. Additionally, these giant papillae can sometimes be seen near the limbus and, while relatively uncommon, symblepharon formation and conjunctival fibrosis can occur.
• Limbal signs include thickening and opacification of the limbal conjunctiva, as well as gelatinous-appearing and sometime confluent limbal papillae. Perilimbal Horner-Trantas dots are focal white limbal dots consisting of degenerated epithelial cells and eosinophils. Limbal disease can result in a limbal stem cell deficiency that can lead to pannus formation with corneal neovascularization.
• Corneal signs vary according to the severity of the disease process. Punctate epithelial erosions or keratitis can coalesce into macro-erosions of the epithelium. Plaques containing fibrin and mucus can accumulate into macro-erosion-forming Shield ulcers. Corneal neovascularization can ensue, and resolution can leave a characteristic ring-like scar. A waxing and waning gray-white lipid depositing in the peripheral, superficial stroma can occur and is known as pseudogerontoxon. Keratoconus has been shown to be more prominent in VKC patients as well; possibly because patients with chronic eye irritation increase their eye rubbing.

Differential diagnosis

The main differential diagnosis to be considered is atopic keratoconjunctivitis (AKC). AKC typically has an age of onset in the 2nd to 5th decade, where as onset of VKC is typically prior to age 10. Conjunctival involvement is classically on the upper tarsus in VKC and on the lower tarsus in AKC. Additionally, AKC is typically more chronic in nature and more commonly results in scarring of the cornea and conjunctival cicatrization, whereas VKC is typically more self limiting. Additional differential diagnoses to consider are seasonal allergic conjunctivitis and giant papillary conjunctivitis.

Management

Treatment

Removal of any and all possible allergens, as well as conservative management such as cool compresses and lid scrubs, constitute the first line of therapy. A topical antihistamine may only work in mild cases. Topical mast cell stabilizers (cromolyn sodium, nedocromil sodium, and lodoxamide) are typically used with topical antihistamines and have been shown to be effective in moderate presentations of VKC. Mast-cell stabilizers have a loading period to reach their full therapeutic effect. If seasonal recurrence is known, it is suggested that mast-cell stabilization therapy be initiated prior to the season in which symptoms are encountered and continued throughout the season. Dual-action agents with both H1-blocking mechanism and mast-cell stabilization have the benefits of working immediately and providing long-term disease-modifying effects. Topical corticosteroids are typically the most effective. High pulse dose with quick tapering and use of low-absorption corticosteroids (fluoromethelone, loteprednol, rimexolone, etc.) is preferred when using topical corticosteroid therapy. Oral corticosteroids can be considered in sight-threatening conditions. Chronic abuse of steroid drops can lead to glaucoma or cataracts and patients should be advised against unsupervised use of topical steroids.

The management of a shield ulcer typically involves a combination of treatment approaches. These may include topical medications such as corticosteroids, artificial tears, and possibly cyclosporine. Surgical options might include debridement and amniotic membrane transplantation. The specific treatment plan will depend on the severity and grade of the ulcer.

Supratarsal injection of local corticosteroid (triamcinolone or dexamethasone) into the upper tarsal papillae can sometimes offer short-term relief as well.

Long-term immunomodulation with steroid-sparing agents such as cyclosporine and tacrolimus is often needed. Topical cyclosporin-A in concentrations of 0.05% to 2% has been shown to decrease inflammatory cytokines and the signs and symptoms of treated VKC patients. Tacrolimus 0.1% topically has also been shown to improve signs and symptoms of disease, with 1 study showing improvement even in patients unresponsive to 0.1% topical cyclosporine. A study comparing the use of 0.1% tacrolimus ophthalmic ointment dosed twice a day to 2% CsA eye drops 4 times a day for the treatment of VKC did not find a statistically significant difference in signs or symptoms or side effects between the 2 groups.

Additionally, adult patients with VKC may respond more favorably to topical cyclosporin therapy. Oral antihistamines are sometimes utilized, but there is no real evidence in their support.

Systemic immunotherapy is also an option, especially for those patients with underlying systemic atopic disease, such as atopic dermatitis and asthma. There are case reports of the successful use of omalizumab, an anti-IgE monoclonal antibody, in patients with VKC recalcitrant to other treatment modalities, but this remains an off-label use. Dupilumab is a human monoclonal antibody against interleukin-4 receptor alpha used in the treatment of atopic dermatitis. There is currently a multi-center, double-masked, randomized, and placebo-controlled, parallel-group study that is evaluating the safety and efficacy of dupilumab in the treatment of signs and symptoms of individuals with atopic keratoconjunctivitis (NCT04296864), and may also play a role in treating vernal disease in those patients older than 12 years. However, dupilumab has been found to itself induce atopic keratoconjunctivitis, compared to placebo, in treated patients, so its role as a primary treatment is debatable.

Prognosis

Generally, VKC is a rather benign and self-limiting disease that may resolve with age or spontaneously at puberty. Nonetheless, the sometimes debilitating nature of this disease when it is active necessitates therapy to control symptoms. Complications typically arise from occasional corneal scarring and the unsupervised used of topical corticosteroids . In some patients, symptoms may persist beyond childhood, which in some cases may represent a conversion to an adult form of atopic keratoconjunctivitis. This persistence into adulthood has been shown to be as high as 12%.