Alex Hui, OD, PhD, GradCertOcTher, FAAO, is a Senior Lecturer at the School of Optometry and Vision Science at UNSW Sydney. He completed his optometry training and PhD at the University of Waterloo and the Centre for Contact Lens Research, where he investigated drug releasing contact lenses. His research interests include contact lenses, ocular therapeutics, myopia control and drug delivery.
Pall et al. Management of ocular allergy itch with an antihistamine-releasing contact lens. Cornea. 2019;38(6):713-717
Introduction
There has been growing interest in contact
lens applications beyond simple refractive correction, with their potential to
deliver drugs to the eye being a focus of research interest for some time. Understandably,
most of this work has been confined to the laboratory or in animal models,
however the feature article by Pall et al presents results from two parallel
human clinical trials investigating a new ketotifen-loaded contact lens. The
studies were relatively large, enrolling a total of 244 participants, who wore
control and test lenses at multiple sites, and represent one of the first large
scale trials of drug-releasing contact lenses.
Ketotifen is a drug that possesses both
antihistamine and mast-cell stabilising properties, and when loaded into a
contact lens, is designed to help alleviate the signs and symptoms of allergic
conjunctivitis. Those symptoms include itching, which often results in
eye-rubbing by the patient and subsequent further exacerbation of symptoms. The
authors mention how contact lens wearers may revert to spectacles during
allergy season to avoid these issues.
The incorporation of a pharmaceutical agent
into the lens itself to reduce these symptoms would thus be worthwhile,
improving quality of life for these patients, helping to maintain their contact
lens wear and also preventing the need for use of additional pharmaceutical
drops during lens wear.
Study Design
The study was a randomized, placebo-controlled
design. Participants were required to be regular contact lens wearers with a
positive history of allergy symptoms, while also showing positive allergic
responses on skin tests. Subjects as young as 8 years of age were eligible to
be enrolled, with the youngest actual participant being 12 years of age. To
test the efficacy of the drug-releasing lenses, the conjunctival allergen
challenge (CAC) was utilized. The CAC involves instillation of a known amount
of allergen to produce a reliable and repeated allergic response on the eye.
This allows for the effects of treatments such as anti-allergy agents to be
quantified when the CAC is repeated. The CAC is a validated method that is
utilized by the US Food and Drug Administration to evaluate and approve
ophthalmic anti-allergy medications. The study randomized participants into
wearing control or treatment lenses in both eyes, or into a third group which
had one eye with the test lens and the other with the control. On two separate
visits the CAC was administered while wearing their assigned lenses, with the
only difference being the time the CAC occurred after lens insertion. One time point
was after 15 minutes to establish the onset of how quickly the drug-lens system
was able to suppress itch symptoms, with the other, on a separate visit, was
after 12 hours of lens wear to see if the anti-allergy effect was prolonged.
Results
The primary method used to evaluate
drug-lens system effectiveness was participant reported itch symptoms on a 0-4
scale. For the CAC, a difference of 1 in itch scores is considered clinically
significant, a threshold which was met at all time points after the CAC was
administered, when the control and test lenses were compared. Questioning of
the patient’s itch scores 3, 5 and 7 minutes after allergen exposure
demonstrated a clear difference in itch symptoms reported in eyes wearing
control versus test lenses, reaching statistical significance and demonstrating
test lens efficacy. The paper also reported the onset and longevity of the
anti-allergic effect, with differences in itch symptoms post the CAC evident
after only 15 minutes of wear, and persisting even after 12 hours of wear. The paper
also reported several secondary endpoints, which included gradings of
conjunctival, ciliary and episcleral redness. While they reported that there
were statistically significant differences in these measurements in the
expected direction, they did not reach their defined threshold for clinical relevance.
Clinical Implications
This is the first reported large-scale
clinical trial in humans utilizing a drug-releasing contact lens. The ability
of the ketotifen-contact lens combination in preventing allergy symptoms in the
face of an allergen challenge was evident from the data, demonstrating the
feasibility of using a drug-lens system to control symptoms of allergy for a
prolonged period. Importantly, the study also did not report any major adverse
events when these lenses were used and suggested that these drug releasing lenses
were well tolerated when worn. This study has provided evidence of the
feasibility of contact lens drug delivery. Importantly it employed the same standard
CAC test utilized to test ocular anti-allergy pharmaceuticals, suggesting that
it has cleared similar hurdles to therapeutic eye drops being considered for regulatory
approval. This study will provide avenues for the field of drug-releasing
contact lenses to be furthered. Follow up studies comparing these lenses versus
the use of eye drops will allow for demonstration of the differences in drug
delivery method on patient signs, symptoms, management and compliance.
