Topical 0.03 % tacrolimus for subepithelial infiltrates secondary to adenoviral keratoconjunctivitis

  • Eliya Levinger
  • Omer Trivizki
  • Yonathan Shachar
  • Samuel Levinger
  • David Verssano
Inflammatory Disorders

Abstract

Objective

To determine the safety and efficacy of topical 0.03 % tacrolimus ointment treatment for subepithelial corneal infiltrates (SEIs).

Methods

This prospective non-controlled interventional case series included patients with SEIs who had been previously treated with topical corticosteroids with either no improvement or the medication being withdrawn due to associated intraocular pressure (IOP) elevation. The patients were treated with 0.03 % tacrolimus ointment twice daily for 22 weeks (including a 1-month washout). The objective data were best-corrected Snellen visual acuity (BCVA), IOP, and full ocular examination results, including SEI severity and the Schirmer test. The subjective data were the patients’ responses to a questionnaire at all follow-up visits.

Results

The patients consisted of five males (45 %) and six females (55 %) (mean age 50 ± 11 years) who were followed up for an average of 22 weeks. The mean BCVA (logarithm of the minimum angle of resolution [logMAR]) before and after treatment was 0.34 ± 0.09 and 0.08 ± 0.04 respectively (p = 0.042). All the patients evidenced significant objective clinical improvement, and none had a severe degree of SEI at the end of the treatment. The patients reported considerable reduction in the severity of their symptoms (foreign body sensation, glare, etc.). Three patients were excluded due to side-effects (one had severe dizziness and discomfort), and their data were excluded from the study.

Conclusion

Topical tacrolimus 0.03 % is a safe and effective alternative treatment in patients with SEIs who do not respond to other treatment modalities or have untoward side-effects from topical steroids.

Keywords

Adenoviral keratoconjunctivitis Subepithelial corneal infiltrates Tacrolimus Topical 

References

  1. 1.
    Hillenkamp J, Reinhard T, Ross RS, Böhringer D, Cartsburg O, Roggendorf M, De Clercq E, Godehardt E, Sundmacher R (2002) The effects of cidofovir 1% with and without cyclosporin A 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study. Ophthalmology 109:845–850PubMedCrossRefGoogle Scholar
  2. 2.
    Gordon YJ, Araullo-Cruz T, Romanowski EG (1998) The effects of topical nonsteroidal anti-inflammatory drugs on adenoviral replication. Arch Ophthalmol 116:900–905PubMedCrossRefGoogle Scholar
  3. 3.
    Hillenkamp J, Reinhard T, Ross RS, Böhringer D, Cartsburg O, Roggendorf M, De Clercq E, Godehardt E, Sundmacher R (2001) Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine: a controlled clinical pilot study. Arch Ophthalmol 119:1487–1491PubMedCrossRefGoogle Scholar
  4. 4.
    Lund OE, Stefani FH (1978) Corneal histology after epidemic keratoconjunctivitis. Arch Ophthalmol 96:2085–2088PubMedCrossRefGoogle Scholar
  5. 5.
    Sahin A, Bozkurt B, Irkec M (2008) Topical cyclosporine a in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up. Cornea 27:193–195PubMedCrossRefGoogle Scholar
  6. 6.
    Ozcan AA, Ersoz TR, Dulger E (2007) Management of severe allergic conjunctivitis with topical cyclosporin a 0.05% eyedrops. Cornea 26:1035–1038PubMedCrossRefGoogle Scholar
  7. 7.
    Doan S, Gabison E, Abitbol O, Gatinel D, Chast F, Hoang-Xuan T (2007) Efficacy of topical 2% cyclosporine A as a steroid-sparing agent in steroid-dependent vernal keratoconjunctivitis. J Fr Ophtalmol 30:697–701PubMedCrossRefGoogle Scholar
  8. 8.
    Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H, Imanaka H (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot 40:1249–1255PubMedCrossRefGoogle Scholar
  9. 9.
    Gallego-Pinazo R, Dolz-Marco R, Martínez-Castillo S, Arévalo JF, Díaz-Llopis M (2013) Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis. Inflamm Allergy Drug Targets 12:38–45PubMedCrossRefGoogle Scholar
  10. 10.
    Dhaliwal JS, Mason BF, Kaufman SC (2008) Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty. Cornea 27:488–493PubMedCrossRefGoogle Scholar
  11. 11.
    Meyer-Rüsenberg B, Loderstädt U, Richard G, Kaulfers P-M, Gesser C (2011) Epidemic keratoconjunctivitis: the current situation and recommendations for prevention and treatment. Dtsch Arztebl Int 108:475–480PubMedCentralPubMedGoogle Scholar
  12. 12.
    Shiuey Y, Ambati BK, Adamis AP (2000) A randomized, double-masked trial of topical ketorolac versus artificial tears for treatment of viral conjunctivitis. Ophthalmology 107:1512–1517PubMedCrossRefGoogle Scholar
  13. 13.
    Kowalski RP, Foulks GN, Gordon YJ (2000) Comparison of treatment regimens for ocular infections: community vs academic practice. Ann Ophthalmol 32:295–300CrossRefGoogle Scholar
  14. 14.
    Romanowski EG, Yates KA, Gordon YJ (2002) Topical corticosteroids of limited potency promote adenovirus replication in the Ad5/NZW rabbit ocular model. Cornea 21:289–291PubMedCrossRefGoogle Scholar
  15. 15.
    Romanowski EG, Pless P, Yates KA, Gordon YJ (2005) Topical cyclosporine A inhibits subepithelial immune infiltrates but also promotes viral shedding in experimental adenovirus models. Cornea 24:86–91PubMedCrossRefGoogle Scholar
  16. 16.
    Lucchina S, Parvex SL, Biegger P, Fusetti C (2009) FK-506 ointment: an effective adjuvant therapy to treat a dramatic case of pyoderma gangrenosum of unilateral hand. Chin J Traumatol 12:181–183PubMedGoogle Scholar
  17. 17.
    Lauerma AI, Granlund H, Reitamo S (1997) Use of the newer immunosuppressive agents in dermatology. BioDrugs 8:96–106PubMedCrossRefGoogle Scholar
  18. 18.
    Caffier PP, Harth W, Mayelzadeh B, Haupt H, Sedlmaier B (2007) Tacrolimus: a new option in therapy-resistant chronic external otitis. Laryngoscope 117:1046–1052PubMedCrossRefGoogle Scholar
  19. 19.
    Kymionis GD, Kankariya VP, Kontadakis GA (2012) Tacrolimus ointment 0.03% for treatment of refractory childhood phlyctenular keratoconjunctivitis. Cornea 31:950–952PubMedCrossRefGoogle Scholar
  20. 20.
    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 33:545–549PubMedCrossRefGoogle Scholar
  21. 21.
    MedLine Plus (2013) Tacrolimus TM Drug Insert. National Institutes of Health (nlm.nih.gov)Google Scholar
  22. 22.
    Ebihara N, Ohashi Y, Fujishima H, Fukushima A, Nakagawa Y, Namba K, Okamoto S, Shoji J, Takamura E, Uchio E, Miyazaki D (2012) Blood level of tacrolimus in patients with severe allergic conjunctivitis treated by 0.1% tacrolimus ophthalmic suspension. Allergol Int 61:275–282PubMedGoogle Scholar
  23. 23.
    Ohashi Y, Ebihara N, Fujishima H, Fukushima A, Kumagai N, Nakagawa Y, Namba K, Okamoto S, Shoji J, Takamura E, Hayashi K (2010) A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther 26:165–174PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Eliya Levinger
    • 1
    • 2
  • Omer Trivizki
    • 1
    • 2
  • Yonathan Shachar
    • 1
  • Samuel Levinger
    • 2
  • David Verssano
    • 1
  1. 1.Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel, affiliated to the Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  2. 2.Enaim Medical CenterTel-AvivIsrael

Personalised recommendations