Iberoamerican Journal of Medicine
Iberoamerican Journal of Medicine
Original article

Application of diphenydramine ointment to the eyelids for allergic conjunctivitis

Mitsuhiro Kamimura, Takako Ohnishi, Hisao Terada, Atsuto Mouri, Takahiro Naoi, Hiroaki Todo, Kenji Sugibayashi

Downloads: 4
Views: 7587


Introduction: Allergic conjunctivitis is treated with oral anti-allergy agents or topical eye drops, but the response is often incomplete, and symptoms persist. We considered that topical treatment with an antihistamine ointment (diphenhydramine-Restamin Cream®) on the eyelids could be effective as supplemental therapy. This study investigates the efficacy and safety of Restamin Cream® for allergic conjunctivitis.
Methods: In patients with allergic conjunctivitis, Restamin Cream® was applied to both eyelids twice a day for 2 weeks. There was a 2-week observation period before treatment and a 2-week washout period after treatment. Patients recorded symptoms (eye itching and watering) on a visual analogue scale for the entire 6-week period. Assessment of quality of life, evaluation of conjunctivitis, and measurement of visual acuity and intraocular pressure were conducted at the start of observation, at initiation of treatment, at completion of treatment, and at the end of washout.
Results: 7 patients were enrolled; 5 completed the study and 2 discontinued due to adverse reactions. The quality of life score and objective ocular findings improved in all 5 patients. Visual analogue scale scores for itching and watering also improved significantly in 3 and 2 patients, respectively. Adverse reactions included local skin irritation in 3/7 patients, and transient blurred vision and eye pain in 1 patient each. There were no changes of visual acuity or intraocular pressure.
Conclusions: Application of diphenhydramine ointment to the eyelids was effective for allergic conjunctivitis.


Allergic; Conjunctivitis; Antihistamines; Asthma; Conjunctiva; Topical administration


1. Kari O, Saari KM. Updates in the treatment of ocular allergies. J Asthma Allergy. 2010;3:149-58. doi: 10.2147/JAA.S13705.
2. Berger W, Abelson MB, Gomes PJ, Beck M, Kimura S, Westbrook T, et al. Effects of adjuvant therapy with 0.1% olopatadine hydrochloride ophthalmic solution on quality of life in patients with allergic rhinitis using systemic or nasal therapy. Ann Allergy Asthma Immunol. 2005;95(4):361-71. doi: 10.1016/S1081-1206(10)61155-6.
3. Gallacchi G, Marcolongo R. Pharmacokinetics of diclofenac hydroxyethylpyrrolidine (DHEP) plasters in patients with monolateral knee joint effusion. Drugs Exp Clin Res. 1993;19(3):95-7.
4. Sugibayashi K, Yanagimoto G, Hayashi T, Seki T, Juni K, Morimoto Y. Analysis of skin disposition of flurbiprofen after topical application in hairless rats. J Control Release. 1999;62(1-2):193-200. doi: 10.1016/s0168-3659(99)00038-3.
5. Yanagimoto G, Hayashi T, Hasegawa T, Seki T, Juni K, Sugibayashi K, Morimoto Y. Skin disposition of drugs after topical application in hairless rats. Chem Pharm Bull (Tokyo). 1999;47(6):749-54. doi: 10.1248/cpb.47.749.
6. Mills PC, Magnusson BM, Cross SE. Penetration of a topically applied nonsteroidal anti-inflammatory drug into local tissues and synovial fluid of dogs. Am J Vet Res. 2005;66(7):1128-32. doi: 10.2460/ajvr.2005.66.1128.
7. Singh P, Roberts MS. Deep tissue penetration of bases and steroids after dermal application in rat. J Pharm Pharmacol. 1994;46(12):956-64. doi: 10.1111/j.2042-7158.1994.tb03250.x.
8. Singh P, Roberts MS. Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application. J Pharmacol Exp Ther. 1994;268(1):144-51.
9. Fukagawa K, Fujishima H, Fukushima A, Sumi T, Okamoto S, Shoji J, et al. [A quality of life questionnaire for Japanese allergic conjunctival disease]. Nippon Ganka Gakkai Zasshi. 2012;116(5):494-502.
10. Tsubota K, Monden Y, Yagi Y, Goto E, Shimmura S. New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery. Br J Ophthalmol. 1999;83(7):767-70. doi: 10.1136/bjo.83.7.767.
11. See GL, Sagesaka A, Sugasawa S, Todo H, Sugibayashi K. Eyelid skin as a potential site for drug delivery to conjunctiva and ocular tissues. Int J Pharm. 2017;533(1):198-205. doi: 10.1016/j.ijpharm.2017.09.070.
12. Kimura C, Tojo K. Development of a stick-type transdermal eyelid delivery system of ketotifen fumarate for ophthalmic diseases. Chem Pharm Bull (Tokyo). 2007;55(7):1002-5. doi: 10.1248/cpb.55.1002.
13. Boddu SH, Gupta H, Bonam SP. Preclinical evaluation of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery. Int J Pharm. 2014;470(1-2):158-61. doi: 10.1016/j.ijpharm.2014.04.057.
14. Landeck L, John SM, Geier J. Topical ophthalmic agents as allergens in periorbital dermatitis. Br J Ophthalmol. 2014;98(2):259-62. doi: 10.1136/bjophthalmol-2013-304197.
15. Amin KA, Belsito DV. The aetiology of eyelid dermatitis: a 10-year retrospective analysis. Contact Dermatitis. 2006;55(5):280-5. doi: 10.1111/j.1600-0536.2006.00927.x.
16. Moreira J, Gonçalves R, Coelho P, Maio T. Eyelid Dermatitis Caused by Allergic Contact to Acrylates in Artificial Nails. Dermatol Reports. 2017;9(1):7198. doi: 10.4081/dr.2017.7198.
17. Guin JD. Eyelid dermatitis: experience in 203 cases. J Am Acad Dermatol. 2002;47(5):755-65. doi: 10.1067/mjd.2002.122736.
18. Löffler H, Happle R. Profile of irritant patch testing with detergents: sodium lauryl sulfate, sodium laureth sulfate and alkyl polyglucoside. Contact Dermatitis. 2003;48(1):26-32. doi: 10.1034/j.1600-0536.2003.480105.x.
19. Marrakchi S, Maibach HI. Sodium lauryl sulfate-induced irritation in the human face: regional and age-related differences. Skin Pharmacol Physiol. 2006;19(3):177-80. doi: 10.1159/000093112.
20. Teixeira V, Cabral R, Gonçalo M. Exuberant connubial allergic contact dermatitis from diphenhydramine. Cutan Ocul Toxicol. 2014;33(1):82-4. doi: 10.3109/15569527.2013.812106.
21. Fernández-Jorge B, Goday Buján J, Fernández-Torres R, Rodríguez-Lojo R, Fonseca E. Concomitant allergic contact dermatitis from diphenhydramine and metronidazole. Contact Dermatitis. 2008;59(2):115-6. doi: 10.1111/j.1600-0536.2008.01332.x.

Submitted date:

Reviewed date:

Accepted date:

Publication date:

5ffaf0d80e88255549e88747 iberoamericanjm Articles
Links & Downloads

Iberoam J Med

Share this page
Page Sections