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Dermatologic tacrolimus ointment on the eyelids for steroid-refractory vernal keratoconjunctivitis

  • Fang-Yu Liu
  • Hsin-Yu Liu
  • Hsiao-Sang Chu
  • Wei-Li Chen
  • Fung-Rong Hu
  • I-Jong WangEmail author
Cornea
  • 69 Downloads

Abstract

Purpose

The study aims to evaluate the therapeutic effects of dermatologic tacrolimus ointment on eyelids to treat refractory vernal keratoconjunctivitis (VKC).

Method

This institutional study examined the effects of steroid treatment for 10 patients diagnosed with severe VKC refractory to steroid treatment. Patients received 0.1% dermatologic topical tacrolimus treatment on their eyelids once or twice daily for concomitant atopic dermatitis. The therapeutic outcomes were evaluated according to change in severity of clinical findings recorded with serial external ocular photography and change in requirement for steroid treatment.

Results

Clinical signs and symptoms improved substantially after tacrolimus treatment. Significant reduction in size of papillae, decrease of discharge, improvement in hyperemia, and shield ulcer healing with re-epithelization were observed in all patients. Six out of 10 (60%) patients did not receive steroid treatment. Long-term maintenance of tacrolimus was required to prevent episodic exacerbation. Patients’ only treatment-related complaints were of mild burning sensations during medication application to eyelids, and this sensation disappeared a few days after treatment.

Conclusions

Application of 0.1% dermatologic tacrolimus ointment to eyelids is effective and safe in the treatment of refractory VKC in patients with concomitant atopic dermatitis. This treatment may serve as a substitute for or decrease the requirement of steroid treatment.

Keywords

Vernal keratoconjunctivitis Steroid Dermatologic tacrolimus ointment Eyelid 

Notes

Funding

This study received no funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not present any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all participants included in the study.

References

  1. 1.
    Shaker M, Salcone E (2016) An update on ocular allergy. Curr Opin Allergy Clin Immunol 16:505–510.  https://doi.org/10.1097/ACI.0000000000000299 CrossRefGoogle Scholar
  2. 2.
    Bonini S, Bonini S, Lambiase A, Marchi S, Pasqualetti P, Zuccaro O, Rama P, Magrini L, Juhas T, Bucci MG (2000) Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term follow-up. Ophthalmology 107:1157–1163CrossRefGoogle Scholar
  3. 3.
    Bonini S, Sacchetti M, Mantelli F, Lambiase A (2007) Clinical grading of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol 7:436–441.  https://doi.org/10.1097/ACI.0b013e3282efb726 CrossRefGoogle Scholar
  4. 4.
    Takamura E, Uchio E, Ebihara N, Ohno S, Ohashi Y, Okamoto S, Kumagai N, Satake Y, Shoji J, Nakagawa Y, Namba K, Fukagawa K, Fukushima A, Fujishima H, Japanese Society of A (2017) Japanese guidelines for allergic conjunctival diseases 2017. Allergol Int 66:220–229.  https://doi.org/10.1016/j.alit.2016.12.004 CrossRefGoogle Scholar
  5. 5.
    Addis H, Jeng BH (2018) Vernal keratoconjunctivitis. Clin Ophthalmol 12:119–123.  https://doi.org/10.2147/OPTH.S129552 CrossRefGoogle Scholar
  6. 6.
    O'Brien TP (2013) Allergic conjunctivitis: an update on diagnosis and management. Curr Opin Allergy Clin Immunol 13:543–549.  https://doi.org/10.1097/ACI.0b013e328364ec3a CrossRefGoogle Scholar
  7. 7.
    De Smedt S, Wildner G, Kestelyn P (2013) Vernal keratoconjunctivitis: an update. Br J Ophthalmol 97:9–14.  https://doi.org/10.1136/bjophthalmol-2011-301376 CrossRefGoogle Scholar
  8. 8.
    Verin P, Allewaert R, Joyaux JC, Piozzi E, Koliopoulos J, Bloch-Michel E, Lodoxamide Study G (2001) Comparison of lodoxamide 0.1% ophthalmic solution and levocabastine 0.05% ophthalmic suspension in vernal keratoconjunctivitis. Eur J Ophthalmol 11:120–125CrossRefGoogle Scholar
  9. 9.
    Corum I, Yeniad B, Bilgin LK, Ilhan R (2005) Efficiency of olopatadine hydrochloride 0.1% in the treatment of vernal keratoconjunctivitis and goblet cell density. J Ocul Pharmacol Ther 21:400–405.  https://doi.org/10.1089/jop.2005.21.400 CrossRefGoogle Scholar
  10. 10.
    D'Angelo G, Lambiase A, Cortes M, Sgrulletta R, Pasqualetti R, Lamagna A, Bonini S (2003) Preservative-free diclofenac sodium 0.1% for vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 241:192–195.  https://doi.org/10.1007/s00417-002-0612-6 CrossRefGoogle Scholar
  11. 11.
    Tabbara KF, al-Kharashi SA (1999) Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis. Br J Ophthalmol 83:180–184CrossRefGoogle Scholar
  12. 12.
    Oner V, Turkcu FM, Tas M, Alakus MF, Iscan Y (2012) Topical loteprednol etabonate 0.5% for treatment of vernal keratoconjunctivitis: efficacy and safety. Jpn J Ophthalmol 56:312–318.  https://doi.org/10.1007/s10384-012-0152-5 CrossRefGoogle Scholar
  13. 13.
    Tzu JH, Utine CA, Stern ME, Akpek EK (2012) Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis. Cornea 31:649–654.  https://doi.org/10.1097/ICO.0b013e31822481c2 CrossRefGoogle Scholar
  14. 14.
    Saini JS, Gupta A, Pandey SK, Gupta V, Gupta P (1999) Efficacy of supratarsal dexamethasone versus triamcinolone injection in recalcitrant vernal keratoconjunctivitis. Acta Ophthalmol Scand 77:515–518CrossRefGoogle Scholar
  15. 15.
    Holsclaw DS, Whitcher JP, Wong IG, Margolis TP (1996) Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J Ophthalmol 121:243–249CrossRefGoogle Scholar
  16. 16.
    Bleik JH, Tabbara KF (1991) Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology 98:1679–1684CrossRefGoogle Scholar
  17. 17.
    Gupta V, Sahu PK (2001) Topical cyclosporin A in the management of vernal keratoconjunctivitis. Eye (Lond) 15:39–41.  https://doi.org/10.1038/eye.2001.10 CrossRefGoogle Scholar
  18. 18.
    De Smedt S, Nkurikiye J, Fonteyne Y, Tuft S, De Bacquer D, Gilbert C, Kestelyn P (2012) Topical ciclosporin in the treatment of vernal keratoconjunctivitis in Rwanda, Central Africa: a prospective, randomised, double-masked, controlled clinical trial. Br J Ophthalmol 96:323–328.  https://doi.org/10.1136/bjophthalmol-2011-300415 CrossRefGoogle Scholar
  19. 19.
    Spadavecchia L, Fanelli P, Tesse R, Brunetti L, Cardinale F, Bellizzi M, Rizzo G, Procoli U, Bellizzi G, Armenio L (2006) Efficacy of 1.25% and 1% topical cyclosporine in the treatment of severe vernal keratoconjunctivitis in childhood. Pediatr Allergy Immunol 17:527–532.  https://doi.org/10.1111/j.1399-3038.2006.00427.x CrossRefGoogle Scholar
  20. 20.
    Anzaar F, Gallagher MJ, Bhat P, Arif M, Farooqui S, Foster CS (2008) Use of systemic T-lymphocyte signal transduction inhibitors in the treatment of atopic keratoconjunctivitis. Cornea 27:884–888.  https://doi.org/10.1097/ICO.0b013e318172fbb1 CrossRefGoogle Scholar
  21. 21.
    Ueta M, Sotozono C, Koga A, Yokoi N, Kinoshita S (2014) Usefulness of a new therapy using rebamipide eyedrops in patients with VKC/AKC refractory to conventional anti-allergic treatments. Allergol Int 63:75–81.  https://doi.org/10.2332/allergolint.13-OA-0605 CrossRefGoogle Scholar
  22. 22.
    Pucci N, Caputo R, di Grande L, de Libero C, Mori F, Barni S, di Simone L, Calvani A, Rusconi F, Novembre E (2015) Tacrolimus vs. cyclosporine eyedrops in severe cyclosporine-resistant vernal keratoconjunctivitis: a randomized, comparative, double-blind, crossover study. Pediatr Allergy Immunol 26:256–261.  https://doi.org/10.1111/pai.12360 CrossRefGoogle Scholar
  23. 23.
    Fukushima A, Ohashi Y, Ebihara N, Uchio E, Okamoto S, Kumagai N, Shoji J, Takamura E, Nakagawa Y, Namba K, Fujishima H, Miyazaki D (2014) Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement. Br J Ophthalmol 98:1023–1027.  https://doi.org/10.1136/bjophthalmol-2013-304453 CrossRefGoogle Scholar
  24. 24.
    Leonardi A, Secchi AG (2003) Vernal keratoconjunctivitis. Int Ophthalmol Clin 43:41–58CrossRefGoogle Scholar
  25. 25.
    Tanaka M, Dogru M, Takano Y, Miyake-Kashima M, Asano-Kato N, Fukagawa K, Tsubota K, Fujishima H (2006) Quantitative evaluation of the early changes in ocular surface inflammation following MMC-aided papillary resection in severe allergic patients with corneal complications. Cornea 25:281–285.  https://doi.org/10.1097/01.ico.0000183533.14899.8d CrossRefGoogle Scholar
  26. 26.
    Ganong WF (2005) Review of medical physiology (LANGE basic science) 22nd Edition. McGraw-Hill Medical, New York CityGoogle Scholar
  27. 27.
    Sakuma S, Higashi Y, Sato N, Sasakawa T, Sengoku T, Ohkubo Y, Amaya T, Goto T (2001) Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (comparison with steroids). Int Immunopharmacol 1:1219–1226CrossRefGoogle Scholar
  28. 28.
    Al-Amri AM (2014) Long-term follow-up of tacrolimus ointment for treatment of atopic keratoconjunctivitis. Am J Ophthalmol 157:280–286.  https://doi.org/10.1016/j.ajo.2013.10.006 CrossRefGoogle Scholar
  29. 29.
    FDA U (2000) US FDA advisory committee recommends approval of tacrolimus ointment. Skin Therapy Lett 6:5Google Scholar
  30. 30.
    Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, Nagata Y, Hasegawa J, Inoue Y (2008) Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology 115:988–992 e985.  https://doi.org/10.1016/j.ophtha.2007.07.025 CrossRefGoogle Scholar
  31. 31.
    Zribi H, Descamps V, Hoang-Xuan T, Crickx B, Doan S (2009) Dramatic improvement of atopic keratoconjunctivitis after topical treatment with tacrolimus ointment restricted to the eyelids. J Eur Acad Dermatol Venereol 23:489–490.  https://doi.org/10.1111/j.1468-3083.2008.02933.x CrossRefGoogle Scholar
  32. 32.
    Mandelin JM, Remitz A, Virtanen HM, Malmberg LP, Haahtela T, Reitamo S (2010) A 10-year open follow-up of eczema and respiratory symptoms in patients with atopic dermatitis treated with topical tacrolimus for the first 4 years. J Dermatol Treat 21:167–170.  https://doi.org/10.3109/09546630903493329 CrossRefGoogle Scholar
  33. 33.
    Yuan J, Zhai JJ, Chen JQ, Ye CT, Zhou SY (2009) Preparation of 0.05% FK506 suspension eyedrops and its pharmacokinetics after topical ocular administration. J Ocul Pharmacol Ther 25:345–350.  https://doi.org/10.1089/jop.2008.0125 CrossRefGoogle Scholar
  34. 34.
    Attas-Fox L, Barkana Y, Iskhakov V, Rayvich S, Gerber Y, Morad Y, Avni I, Zadok D (2008) Topical tacrolimus 0.03% ointment for intractable allergic conjunctivitis: an open-label pilot study. Curr Eye Res 33:545–549.  https://doi.org/10.1080/02713680802149115 CrossRefGoogle Scholar
  35. 35.
    Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26:1261–1268.  https://doi.org/10.1038/nbt.1504 CrossRefGoogle Scholar
  36. 36.
    Miyazaki D, Fukushima A, Ohashi Y, Ebihara N, Uchio E, Okamoto S, Shoji J, Takamura E, Nakagawa Y, Namba K, Fujishima H (2017) Steroid-sparing effect of 0.1% tacrolimus eye drop for treatment of shield ulcer and corneal epitheliopathy in refractory allergic ocular diseases. Ophthalmology 124:287–294.  https://doi.org/10.1016/j.ophtha.2016.11.002 CrossRefGoogle Scholar
  37. 37.
    Barot RK, Shitole SC, Bhagat N, Patil D, Sawant P, Patil K (2016) Therapeutic effect of 0.1% tacrolimus eye ointment in allergic ocular diseases. J Clin Diagn Res 10:NC05–NC09.  https://doi.org/10.7860/JCDR/2016/17847.7978 Google Scholar
  38. 38.
    Hazarika AK, Singh PK (2015) Efficacy of topical application of 0.03% tacrolimus eye ointment in the management of allergic conjunctivitis. J Nat Sci Biol Med 6:S10–S12.  https://doi.org/10.4103/0976-9668.166051 CrossRefGoogle Scholar
  39. 39.
    Kheirkhah A, Zavareh MK, Farzbod F, Mahbod M, Behrouz MJ (2011) Topical 0.005% tacrolimus eye drop for refractory vernal keratoconjunctivitis. Eye (Lond) 25:872–880.  https://doi.org/10.1038/eye.2011.75 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fang-Yu Liu
    • 1
    • 2
  • Hsin-Yu Liu
    • 1
  • Hsiao-Sang Chu
    • 1
  • Wei-Li Chen
    • 1
  • Fung-Rong Hu
    • 1
  • I-Jong Wang
    • 1
    • 3
    Email author
  1. 1.Department of OphthalmologyNational Taiwan University HospitalTaipeiTaiwan
  2. 2.Department of OphthalmologyTri-Service General HospitalTaipeiTaiwan
  3. 3.Graduate Institute of Biomedical Sciences, School of MedicineChina Medical UniversityTaichungTaiwan

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