Control Vernal Keratoconjunctivitis With Deft Diagnosis, Various Treatment Options

Slit lamp image of an eye with vernal keratoconjunctivitis
Slit lamp image of an eye with vernal keratoconjunctivitis, an allergic reaction causing inflammation of the cornea and conjuntiva, shown under the upper lid.
Andrea Leonardi, MD, Dagny Zhu, MD, and Leonard Bielory, MD, describe this relatively rare ophthalmological condition that can threaten vision if left untreated.

The National Organization for Rare Disorders  (NORD) reported in 2020 that there are more than 7000 rare diseases, and approximately 90% of them do not have an FDA-approved treatment or therapy.1 Although an uncommon diagnosis, the ophthalmic condition vernal keratoconjunctivitis (VKC) now has a dedicated therapeutic treatment option that can, with timely diagnosis and proper treatment, help prevent it from leading to vision loss. This is all the more pressing as most patients in the US who develop VKC are young — approximately 11 years old.2

Here, we provide an overview of the diagnostic challenges of, and treatment recommendations for, this chronic, progressive disorder.

Challenges in Diagnosis

Dr Andrea Leonardi, MD, is a researcher and professor of ophthalmology at the University of Padova who has worked clinically and preclinically on VKC for 30 years. He explained that, since VKC is so rare and primarily presents in pediatric patients (who may never visit an ophthalmology department) many ophthalmologists only ever see a handful of cases in their lifetimes. This, coupled with the lack of any definitive diagnostic lab test, could potentially create conditions for a missed or delayed diagnosis.

In fact, diagnostic delays are common for VKC, and if left untreated, can lead to vision loss, according to a Santen-funded study presented at the American Academy of Pediatric Ophthalmology and Strabismus (AAPOS) 2022 annual meeting.3

In the study, researchers found that 14 of 16 practitioners (4 general ophthalmologists, 4 cornea specialists, 3 pediatric ophthalmologists, 2 ocular immunologists, 1 allergist/immunologist, 1 neuro-ophthalmologist, and 1 optometrist) reported that pediatricians and primary care providers often misdiagnosed and inappropriately treated VKC as allergy or infection. The study also found that approximately 75% of young patients and caregivers underestimated symptom severity, delaying referrals until symptoms became severe. In fact, those more severe symptoms are often the only way the diagnosis is ever made. As one of the study’s authors, Leonard Bielory, MD, explained, vernal conjunctivitis and seasonal, allergic conjunctivitis look the same when a child is developing immunological sensitization, in the year prior to developing symptoms. If vernal conjunctivitis is left untreated, the condition begins to involve the cornea. In the most extreme form, ulcers can form, Dr Bielory said.

Dr Bielory, a professor of medicine, allergy, immunology and ophthalmology at the Hackensack Meridian School of Medicine in Nutley, New Jersey, offered a potential workaround to this diagnostic conundrum. He recommends referring patients to an allergist or immunologist for skin testing to rule out allergic conjunctivitis.

“If the allergy skin testing is negative and the patient has ocular symptoms — even though the cornea’s not involved — you probably have vernal,” he said.

Half of patients with vernal conjunctivitis and VKC are skin test negative to allergens, he explained.

Presentation and Differential Diagnosis

Symptoms of VKC include itching, foreign body sensation, photophobia, redness, watering, and mucoid discharge, according to a 2021 study published in The Ocular Surface.4

Dagny Zhu, MD, cornea, cataract, and refractive surgeon, medical director and partner at NVISION Eye Centers in Rowland Heights, California, says the symptoms range from mild and intermittent (fewer than 4 episodes annually) to severe and chronic, with no period of complete relief.

“Unfortunately, there’s no universal grading system, which makes diagnosis and treatment more difficult,” Dr Zhu said.

She urges ophthalmologists to evert patients’ upper eyelids to avoid overlooking VKC. This procedure can reveal VKC’s classic characteristic of papillary conjunctival reaction, which tends to occur in the upper tarsus and superior limbus, with gelatinous, confluent limbal papillae.4

“There may be gelatinous whitish epithelial infiltrates along the limbus (horners trantas dots). Severe cases can involve the cornea including punctate epithelial erosions, superficial punctate keratitis, and macro erosions or shield ulcers,” said Dr Zhu. “The giant papillae are usually obvious.”

Staining the cornea with fluorescein to determine whether it is involved in presentation is also key, Dr Zhu said. If disproportionate involvement of the superior cornea is seen, ophthalmologists should check whether the cornea is being rubbed, she explained.

Dr Leonardi said that once ophthalmologists are familiar with the condition, diagnosing it tends to be straightforward, unless symptoms are mild or VKC presents in winter or fall. In those cases, clinical history can be especially important.

“In particular, the clinical history of long lasting symptoms in spring and summer exacerbating outdoors, intense itching and photophobia with bilateral redness, tearing and mucus should alarm the pediatrician and the ophthalmologist,” Dr Leonardi said.

Patients may find it difficult to wake up in the morning because of the impact inflammation has when their eyes are closed in the absence of tearing and blinking, he added.

VKC is most commonly mistaken in differential diagnosis with blepharokeratoconjunctivitis, which is associated with meibomian gland dysfunction (MGD) in pediatric patients, Dr Leonardi said. It can also be difficult to diagnose in the rare cases of adult-onset VKC-like disease.

Treatments and Prognosis

Several treatments are available for VKC, including Verkazia® (Cyclosporine Ophthalmic Emulsion, 0.1%, Santen), which obtained approval from the US Food and Drug Administration (FDA) for treatment of VKC in June 2021.5

Verkazia reduces the immunological response without the “shotgun approach” of steroids, and patients can use it longer than they could use steroids, according to Dr Bielory.

Dr Leonardi, who participated in the design and analysis of the VEKTIS study that supported the approval of Verkazia in the European Union, Asia, and the US, says he has used Verkazia with his patients for about a year and has found it effective for reducing VKC symptoms, promoting his patients’ quality of life.

“VKC can be nasty and long lasting for these children,” Dr Leonardi said. “Having a drug that controls the disease in the long term and avoids the use of corticosteroids represents a great improvement in the management of VKC.”

He recommends ophthalmologists consider using a cyclosporine in moderate to severe cases that involve frequent and monthly use of corticosteroids courses, complications or adherence difficulties, or limited therapeutic response.

Dr Zhu offered additional treatment options, such as cool compresses, lid scrubs, preservative-free artificial tears, and antihistamine drops, which she said may be sufficient to manage mild cases of VKC. However, she explained, a quick topical steroid taper tends to be the quickest, most effective method of relieving symptoms of acute flares. Patients with systemic atopic disease may benefit from oral immunotherapy.

“Low potency steroids like loteprednol and fluorometholone have lower side effect profiles,” Dr Zhu said. “For moderate to severe cases, this should be combined with a mast cell stabilizer like cromolyn sodium to keep the disease under control and should be started during the quiescent period (usually just before springtime) as a prophylactic measure for recurrent seasonal cases. Steroid sparing agents like cyclosporine 0.05-2% and tacrolimus 0.1% ointment can also be helpful.”

A 2021 retrospective study published in Cornea that did not include a control group showed tarsal/giant papillae, hyperemia, and limbal papillae reduced significantly in both pediatric patients with seasonal or perennial VKC who took tacrolimus 0.1% eye drops.6 The researchers said patients did not report systemic or local adverse events, apart from a transient stinging sensation.

Surgical management may be necessary in cases of some complications, such as when giant papillae do not respond to medical therapy and repeatedly cause corneal involvement.4

Disclosure: Some of the research referred to in this article was supported by Santen Pharmaceuticals. Please see the original references for a full list of disclosures.


1. National Organization for Rare Disorders. Barriers to rare disease diagnosis, care and treatment in the US: a 30-year comparative analysis. Accessed April 9, 2022.

2. Masters JS. Vernal keratoconjunctivitis. EyeWiki. Updated March 6, 2022. Accessed April 10, 2022.

3. Bielory L, Rose H. The road to diagnosis in VKC: a qualitative study of patients’ and caregivers’ lived experience. Poster presented at the American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, Arizona.

4. Feizi S, Ali Javadi M, Alemzadeh-Ansari M, et al. Management of corneal complications in vernal keratoconjunctivitis: a review. Ocul Surf. 2021;19(1):282-289. doi:10.1016/j.jtos.2020.10.005

5. Santen receives U.S. FDA approval for Verkazia (cyclosporine ophthalmic emulsion, 0.1%) for the treatment of vernal keratoconjunctivitis in children and adults. News release. Santen; June 24, 2021. Accessed April 10, 2022.

6. E. Caputo R, Marziali E, De Libero C, et al. Long-term safety and efficacy of tacrolimus 0.1% in severe pediatric vernal keratoconjunctivitis. Cornea. 2021;40(11):1395-1401. doi:10.1097/ICO.0000000000002751