Allergic eye disease, cyclosporine, paediatric, safety, vernal keratoconjunctivitis
Dominique Bremond-Gignac reports serving as a consultant to Alcon/Novartis, Hoya, Krys, Santen and Théa Laboratories.
This is an expert interview and as such has not undergone the journal’s standard peer review process.
The named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval for the version to be published.
This article is freely accessible at touchOPHTHALMOLOGY.com © Touch Medical Media 2020.
June 02, 2020
July 24, 2020
Dominique Bremond-Gignac, Ophthalmology Department, Necker–Enfants Malades University Hospital, AP-HP, Paris University, OPHTARA Rare Eye Disease Center, Paris, France; INSERM UMRS 1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Université Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 15 rue de l’Ecole de Médecine, 75006 Paris, France. E: firstname.lastname@example.org LinkedIn: www.linkedin.com/in/dominique-bremond-gignac-17a81353/
Expert interview supported by Touch Medical Media, who commissioned the interview in liaison with Santen. Santen were not involved in the development of the content of this article, but performed a review for medical accuracy prior to publication. The views and opinions expressed are those of the author and do not necessarily reflect those of Santen.
Dominique Bremond-Gignac, MD, PhD, FEBO, is Professor of Ophthalmology and Head of the Department of Ophthalmology with a paediatric and ocular surface subspecialty at the University Hospital Necker–Enfants Malades and University of Paris in Paris, France. She graduated in pharmacology and statistics (MSc) and completed her PhD thesis in anatomy. Her activity is distributed across clinical practice teaching and research. Her current practice includes paediatric anterior segment, ocular surface, strabismus and oculo-plastic surgery, as she also graduated in maxillo-facial surgery. Prof. Bremond-Gignac is also in charge of the Orthoptic Department at Paris V University. Her research interests range from the development of oculo-orbital structures to ocular surface morphology. She has acted as a principal investigator for more than 40 clinical research studies, has contributed more than 100 peer-reviewed articles to publications and over 50 book chapters to the ophthalmic literature, and has participated in international congresses and scientific meetings. Last year, she was awarded the Al Biglan Medal of Distinction from the University of Pittsburgh Medical Center Eye Center. Being Involved in visual health in children, she is an executive member of the World Strabismus and Paediatric Ophthalmology Society and President Elect 2021 of the European Association for Vision and Eye Research. She is also the head of two national centres: the CLAIROP Research Clinical Center and the OPHTARA Rare Eye Diseases Center (SENSGENE), accredited by the European Vision Institute Clinical Research Network, and the French Health Ministry and ERN-EYE, a European Reference Network dedicated to rare eye diseases.
Q. Could you tell us about vernal keratoconjunctivitis and its unmet needs?
Vernal keratoconjunctivitis (VKC) is a rare, but severe ocular disease which manifests from keratoconjunctivitis. VKC typically affects children between the ages of 3–17 years; however, the disease resolves in 90% of cases during adolescence.1 Males are more affected than females (sex ratio 3:1).1 VKC can be very severe, impacting quality of life, and can result in school dropout. Affected patients present with tearing, photophobia, mucous discharge, itching and visual impairment. There are two main classifications of VKC: tarsal, which presents with giant papillae of the eyelid; and limbal, which involves epithelial infiltrates called Horner–Trantas dots. A third, mixed variant also exists, but is rarely observed. As VKC is an allergic disease, other manifestations can be present, such as asthma, rhinitis and eczema in varying degrees of severity.
The management of VKC includes frequent washing of the hands and face, prescription of antihistamines and mast cell stabilisers. Until recently, however, the only validated available treatment for severe forms of VKC was steroids. Steroids are efficient, however, iatrogenesis is a common problem, leading to long-term treatment or steroid dependence, glaucoma, corneal herpes recurrence and cataracts; complications which may severely affect vision. The requirement for a different validated medication was urgent. Topical cyclosporine is used for its anti-inflammatory properties and is available in hospitals in different dosages. In order to demonstrate the safety and efficacy of cyclosporine in VKC, the VErnal KeratoconjunctiviTIs Study (VEKTIS) study was initiated.2
Q. What were the objectives of the VEKTIS study?
The VEKTIS study was devised to demonstrate the safety and efficacy of cyclosporine for VKC.2
The objective also included steroid-sparing for affected children to avoid iatrogenicity caused by long-term treatment.
Q. How many patients were included in the VEKTIS study and how was the study designed?
One hundred and sixty-nine patients were included in the VEKTIS study, with a follow-up of
12 months. Of these, 143 patients completed the whole follow-up period.2 Patients were randomised to one of three arms: a vehicle arm, a low-dose arm (twice a day) and a full-dose arm (four times a day).2
Q. What were the key efficacy and safety findings of the study?
Key efficacy was evaluated with a composite score that included Clinical Frailty Scale score, a corneal fluorescein staining score, the need for rescue medication, and the occurrence of corneal ulceration.2 Safety was evaluated with the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire, and adverse events were reported.2,3 Efficacy and safety were demonstrated in the study, showing superiority of the high-dose regimen.2
Q. Have any further studies been planned?
Further clinical studies have not yet been planned. Treatment guidelines for the disease may be reviewed and updated. However, further studies are needed to determine better treatment duration and other allergic keratoconjunctivitis forms. We are thinking of new study designs for
Q. What do the VEKTIS study results mean for the management of vernal keratoconjunctivitis?
The VEKTIS study results are encouraging for the treatment of children with severe VKC and will make it easier for parents to manage the disease.
Physicians are always waiting for clinical studies to demonstrate the safety and efficacy of new pharmaceutical products, not only for VKC, but also in other severe, rare diseases. Published studies with satisfactory results give doctors the opportunity to prescribe eyedrops for VKC in line with recommendations.
For a long time, parents have been seeking eyedrops for their children that can be obtained from regular pharmacies. This will help parents to manage their children’s disease more easily. Other positive observations from the study include improvements in keratitis, key VKC symptoms and a stable quality of life profile.