Eye drop emulsion containing 0.1% cyclosporin (1 mg/mL) for the treatment of severe vernal keratoconjunctivitis: an evidence-based review and place in therapy

Figures & data

Figure 1 Vernal keratoconjunctivitis (VKC): the tarsal form with giant papillae (left panel) and limbal form with Horner-Trantas dots (right panel, black and white arrows).

Figure 2 Vernal keratoconjunctivitis (VKC) corneal alterations as observed with confocal microscopy. (A) Larger and hyperreflective epithelial cells; (B) tortuous superficial nervous plexus; and (C–D) higher concentration of inflammatory cells and activated keratocytes.

Table 1 Most common concentration of CyA eye drops formulations and countries of distribution

Product	CyA	Indications	Distribution
Restasis^® Allergan plc., Coolock, Dublin, Ireland	0.05%	DED	US, Canada, Europe, and other countries
Lacrinmune^® Bausch & Lomb, Rochester, New York, USA	0.05%	KCS	Argentina
TJ Cyporin^® Taejoon Pharma, Wellington 6011, New Zealand	0.05%	KCS with ocular inflammation	South Korea
Cyporin^® Aristopharma Ltd, Bangladesh	0.05%	KCS with ocular inflammation	Bangladesh and Myanmar
Ikervis^® Santen Pharmaceutical Co., Ltd., Osaka 530-8552, Japan	0.1%	DED with severe keratitis	Europe
Verkazia^® Santen Pharmaceutical Co., Ltd., Osaka 530-8552, Japan	0.1%	VKC^a	Germany and UK
Papilock mini^® Santen Pharmaceutical Co., Ltd., Osaka 530-8552, Japan	0.1%	VKC^a	Japan
Modusik-A Ofteno^® Laboratorios Sophia S.A. de C.V. Mexico	0.1%	KCS	Central South America
Cequa^® Sun Pharma Mumbai, Maharashtra, India	0.09%	KCS	US
Optimmune^® Msd Animal Health, Madison, NJ, USA	0.2%	KCS in dogs	World wide

Note: ^aDrugs with specific indication for VKC.

Abbreviations: CyA, cyclosporin A; DED, dry eye disease; KCS, keratoconjunctivitis sicca; VKC, vernal keratoconjunctivitis.

Table 2 Summary of 0.1% (1 mg/mL) concentration CyA studies in VKC patients

VKC study	Ebihara N,et al^Citation62	Baiza-Duran, et al^Citation54	Takamura E, et al^Citation64	Leonardi A, et al^Citation67
Year	2009	2010	2011	2018
Patients	274 KC 320 VKC (mean age 16)	112 VKC (mean age 10.2)	2,597	169 VKC (mean 9.2)
Follow-up	6 months	6 months	6 months	12 months (partial data)
Drops per day	4, 3 or 2 times daily	Twice daily	Not known	4 times daily vs 2 times daily vs vehicle
Formulation	Ophthalmic oil-in-water emulsion	Aqueous solution	Ophthalmic oil-in-water emulsion	Cationic emulsion oil-in-water emulsion
Grading system	Uchio clinical grading system	6 symptoms and 8 clinical signs	6 ocular symptoms, 10 objective signs	Bonini grading scale and modified Oxford scale.
Main outcome	Signs/symptoms improvement after 1 month	Improvement with both 0.1 and 0.05%. 0.1% more effective than 0.05%.	Sign/symptoms decreased through follow-up of 6 months	Signs/symptoms improvement in both high and low dose vs placebo as well as a decrease in rescue medication use.

Abbreviations: CyA, cyclosporin A; VKC, vernal keratoconjunctivitis.

Ebihara N, Ohashi Y, Uchio EA et al. large prospective observational study of novel cyclosporine 0.1% aqueous ophthalmic solution in the treatment of severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2009;25(4):365–372. doi: 10.1089/jop.2008.0103.

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Baiza-Duran LM, González-Villegas AC, Contreras-Rubio Y, et al. Safety and efficacy of topical 0.1% and 0.05% cyclosporine A in an aqueous solution in steroid-dependent vernal keratoconjunctivitis in a population of Mexican children. J Clin Exp Ophthalmol. 2010;1:115. doi:10.4172/2155-9570.1000115.

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Takamura E, Uchio E, Ebihara N, et al. A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis. Nihon Ganka Gakkai Zasshi. 2011;115(6):508–515.

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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. 2018;27. pii: S0161-6420(18)31697-X. doi: 10.1016/j.ophtha.2018.12.027.

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