Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A

Abstract

The incidence of chronic keratoconjunctivitis, which potentially causes long-term loss of visual acuity due to corneal opacity, is considerably less common in children than in adults. It is therefore in danger of being overlooked. In children the appropriate treatment is therefore often introduced too late, or to an insufficient extent. In this article we would like to raise awareness about the diagnosis of chronic keratoconjunctivitis in children, and to present an effective treatment plan for severe stages of the disease. There are two forms of chronic keratoconjunctivitis that occur most frequently in children: hyperergic blepharokeratoconjunctivitis (hBKC) and vernal keratoconjunctivitis (VKC). With hBKC, the patient often has a history of recurring hordeolum and also presents with blepharitis; it is characterized by the marked presence of corneal neovascularization in the lower circumference of the cornea. VKC is typically characterized by changes under the upper eyelid, with marked changes to the superior limbus. If there is a risk of complications involving the cornea, or in the presence of such complications, a consistent long-term topical immunosuppressive and anti-inflammatory treatment is required. Both of these properties are combined in the active ingredient cyclosporine A. Other advantages of topical CSA treatment are its steroid-sparing effect and the long-term reduction of exacerbations. Parents need to be informed about the chronic nature of these two diseases and their tendency to recur; because of these characteristics, treatment, in most cases, should be envisaged for at least one year in order to effectively disrupt the complex immunologic processes. This safeguards the childʼs visual development and prevents amblyopia caused by scarring and astigmatism. We hope that the data presented will lower the barriers related to prescribing CSA for topical eye application in children.

Key words

blepharokeratoconjunctivitis - vernal keratoconjunctivitis - corneal neovascularization - cyclosporine - child - therapy

Publication History

Received: 24 January 2021

Accepted: 08 July 2021

Article published online:
03 November 2021

• References/Literatur

• 1 Hammersmith KM. Blepharokeratoconjunctivitis in children. Curr Opin Ophthalmol 2015; 26: 301-305
• 2 Rodriguez-Garcia A, Gonzalez-Godinez S, Lopez-Rubio S. Blepharokeratoconjunctivitis in childhood: corneal involvement and visual outcome. Eye (Lond) 2016; 30: 438-446
• 3 Pleyer U, Leonardi A. [Vernal keratoconjunctivitis]. Ophthalmologe 2015; 112: 177-189 quiz 190-171
• 4 Kumar S. Vernal keratoconjunctivitis: a major review. Acta Ophthalmol 2009; 87: 133-147
• 5 Leonardi A, Busca F, Motterle L. et al. Case series of 406 vernal keratoconjunctivitis patients: a demographic and epidemiological study. Acta Ophthalmol Scand 2006; 84: 406-410
• 6 Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclosporine: pharmacology and clinical uses. Surv Ophthalmol 2009; 54: 321-338
• 7 Sadrai Z, Hajrasouliha AR, Chauhan S. et al. Effect of topical azithromycin on corneal innate immune responses. Invest Ophthalmol Vis Sci 2011; 52: 2525-2531
• 8 Foulks GN, Borchman D, Yappert M. et al. Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea 2010; 29: 781-788
• 9 Hoffmann F, Wiederholt M. Local treatment of necrotizing scleritis with cyclosporin A. Cornea 1985; 4: 3-7
• 10 BenEzra D, Matamoros N, Cohen E. Treatment of severe vernal keratoconjunctivitis with cyclosporine A eyedrops. Transplant Proc 1988; 20: 644-649
• 11 Zierhut M, Thiel HJ, Weidle EG. et al. Topical treatment of severe corneal ulcers with cyclosporin A. Graefes Arch Clin Exp Ophthalmol 1989; 227: 30-35
• 12 Goichot-Bonnat L, Chemla P, Pouliquen Y. [Cyclosporin A eyedrops in the prevention of high-risk corneal graft rejection. II. Postoperative clinical results]. J Fr Ophtalmol 1987; 10: 213-217
• 13 Hoffmann F, Wiederholt M. [Local treatment of corneal transplants in the human with cyclosporin A]. Klin Monbl Augenheilkd 1985; 187: 92-96
• 14 Levy O, Labbe A, Borderie V. et al. [Topical cyclosporine in ophthalmology: Pharmacology and clinical indications]. J Fr Ophtalmol 2016; 39: 292-307
• 15 Tang-Liu DD, Acheampong A. Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye. Clin Pharmacokinet 2005; 44: 247-261
• 16 Diaz-Llopis M, Menezo JL. Penetration of 2 % cyclosporin eyedrops into human aqueous humour. Br J Ophthalmol 1989; 73: 600-603
• 17 Minguez E, Tiestos MT, Cristobal JA. et al. [Intraocular absorption of cyclosporin A eyedrops]. J Fr Ophtalmol 1992; 15: 263-267
• 18 Pfau B, Kruse FE, Rohrschneider K. et al. [Comparison between local and systemic administration of cyclosporin A on the effective level in conjunctiva, aqueous humor and serum]. Ophthalmologe 1995; 92: 833-839
• 19 Theng J, Zhou L, Tan D. et al. Distribution of cyclosporin A in the cornea after topical or oral administration. J Ocul Pharmacol Ther 2002; 18: 83-88
• 20 Small DS, Acheampong A, Reis B. et al. Blood concentrations of cyclosporin a during long-term treatment with cyclosporin A ophthalmic emulsions in patients with moderate to severe dry eye disease. J Ocul Pharmacol Ther 2002; 18: 411-418
• 21 Bremond-Gignac D, Doan S, Amrane M. et al. Twelve-Month Results of Cyclosporine A Cationic Emulsion in a Randomized Study in Patients With Pediatric Vernal Keratoconjunctivitis. Am J Ophthalmol 2020; 212: 116-126
• 22 Leonardi A, Doan S, Amrane M. et al. A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study. Ophthalmology 2019; 126: 671-681
• 23 Keklikci U, Dursun B, Cingu AK. Topical cyclosporine a 0.05 % eyedrops in the treatment of vernal keratoconjunctivitis – randomized placebo-controlled trial. Adv Clin Exp Med 2014; 23: 455-461
• 24 Doan S, Gabison E, Gatinel D. et al. Topical cyclosporine A in severe steroid-dependent childhood phlyctenular keratoconjunctivitis. Am J Ophthalmol 2006; 141: 62-66
• 25 Flynn TH, Manzouri B, Tuft SJ. Ocular surface squamous neoplasia in an immunosuppressed patient with atopic keratoconjunctivitis. Int Ophthalmol 2012; 32: 471-473
• 26 Rouimi F, Bouillot A, Baudouin C. et al. [Topical cyclosporine A and risk of ocular surface neoplasia]. J Fr Ophtalmol 2018; 41: 122-128
• 27 Lallemand F, Schmitt M, Bourges JL. et al. Cyclosporine A delivery to the eye: A comprehensive review of academic and industrial efforts. Eur J Pharm Biopharm 2017; 117: 14-28
• 28 Rousta ST. Pediatric blepharokeratoconjunctivitis: is there a ‘right’ treatment?. Curr Opin Ophthalmol 2017; 28: 449-453
• 29 Leonardi A. Management of vernal keratoconjunctivitis. Ophthalmol Ther 2013; 2: 73-88