Cyclosporine A Update
New formulations of cyclosporine showing good results in paediatric ocular surface diseases
Newer formulations of cyclosporine A (CsA) are transforming the treatment of severe paediatric allergic ocular surface diseases, with proven efficacy and safety data now available, the 10th EuCornea Congress in Paris, France, heard.
Paediatric Ophthalmologist Dominique Brémond-Gignac MD, Paris, France, prepared an expert update on the use of cyclosporine in allergic conjunctivitis which was delivered by her colleague Dr Frederic Chiambaretta, during the dedicated session on ocular surface diseases in paediatric patients.
Severe allergic conjunctivitis alone is estimated to effect 6-to-30% of the population, in up to 30% of children alone or in association with allergic rhinitis. It is a diagnostic and therapeutic challenge in children; it has multiple clinical forms and ranges from mild to severe, causing loss of quality of life and visual impairment.
Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are rare and potentially debilitating forms, which are characterised by allergic inflammation of the ocular surface, with clinical manifestations involving the tarsal (palpebral) and/or bulbar conjunctiva that can have a seasonal course, but also may be chronic with acute exacerbations, Dr Brémond-Gignac wrote.
Key signs and symptoms of VKC include photophobia, tearing, conjunctival hyperaemia, itching, stringy mucous discharge, giant papillae on the upper tarsal conjunctiva, papillae and gelatinous infiltrates on the limbus with white-yellow nodules (Horner-Trantasdots), superficial punctate keratitis and corneal shield ulcers. VKC is a disease that affects primarily boys and children from age three to 16 years old and usually disappears at adolescence, Dr Brémond-Gignac’s presentation outlined.
Prompt, correct diagnosis and treatment of VKC is key due to the risk of blindness, cataract, glaucoma, epithelium defects and herpes or fungus, and consequently steroid-sparing treatment is important. The immunosuppressant drug CsA is thus an effective treatment, Dr Brémond-Gignac outlined in her ESCRS presentation.
There are a number of different concentrations of CsA (0.05-2mg/ml) available in different countries with different indications. The minimum effective concentration for the treatment of VKC remains unknown, with no studies have compared the efficacy of different concentrations according to Dr Brémond-Gignac’s presentation.
However, newer CsA formulations (0.1%, specific clinical indication for VKA) have shown good efficacy in severe VKA in four key studies to date.
Specifically, Prof Brémond-Gignac’s presentation outlined the results of research she was involved with – the VErnal KeratoconjunctiviTIs Study (VEKTIS), a phase III, multi-centre, double-masked, vehicle-controlled trial that evaluated the efficacy and safety of an investigational therapy for severe VKC, CsA cationic emulsion (CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations.
Paediatric patients (4-18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale) were recruited for the study.
One-hundred-and-sixty-nine patients were randomised to CsA CE 0.1% (1 mg/ml) eye drops four times daily (high dose), CsA CE twice daily (low dose) plus vehicle twice daily, or vehicle four times daily for four months.
Differences in least-squares means versus vehicle for the primary endpoint were statistically significant for both the high-dose (0.76; p=0.007) and the low-dose (0.67; p=0.010) groups, with treatment effect mainly driven by CFS score.
Significant differences were found between both the active treatment groups and vehicle for use of rescue medication. VKC symptoms and patient quality of life (assessed by visual analogue scale and the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire) improved in all three groups, with significant improvements for high-dose (four-times daily) CsA CE versus vehicle.
The study concluded that the efficacy of high-dose CsA CE in improving keratitis, symptoms, and quality of life for those with severe VKC was demonstrated in the recruited patients. In addition, in this study cohort, CsA CE was well tolerated, and the results were maintained during 12 months; “So this is an effective and safe treatment option for these patients.”
Dr Bremond-Gignac’s presentation also emphasised the importance of washing and hygiene for the diseased eyes to optimise results.