ORIGINAL ARTICLE Efficacy of olopatadine hydrochloride 0.1%, emedastine difumarate 0.05%, and loteprednol etabonate 0.5% for Chinese children with seasonal allergic conjunctivitis: a randomized vehicle-controlled study Rui-fen Liu, Xiao-xuan Wu, Xiao Wang, Jing Gao, Jun Zhou and Qi Zhao, MD Background: Allergic conjunctivitis (AC) is a disease of However, there was no statistical significance (p ࣙ 0.05) various agents that affects the physical and mental health shown among the treatment groups. There were no evident of children. Although the most effective therapy has not changes in VA and no clinically significant changes were ob- been found so far, it is essential to explore the considerable served in fundus oculi. therapeutic method. We compared the clinical efficacy of olopatadine, emedastine, loteprednol etabonate (LE), and Conclusion: Aer the treatment, the efficacy presented a vehicle for treating seasonal allergic conjunctivitis (SAC) in similar distribution among the trial groups. C 2016 The Au- Chinese children. thors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC. Methods: Eighty cases of 160 eyes aged from 5 to 10 This is an open access article under the terms of the Cre- years with SAC were available and those subjects were ran- ative Commons Attribution-NonCommercial License, which domly distributed into 4 groups. Both their eyes received permits use, distribution and reproduction in any medium, olopatadine hydrochloride 0.1% twice a day, emedastine provided the original work is properly cited and is not used difumarate 0.05% twice a day, or LE 0.5% 4 times a day, for commercial purposes. respectively, whereas those of the control group received artificial tears (AT) 0.5% 3 times a day. This study was con- Key Words: ducted successfully and the observations were collected SAC; olopatadine hydrochloride; emedastine difumarate; before treatment and on day 8 (±1day)andday15(±2days) LE; vehicle; efficacy aerward. The principal measurement of efficacy was fo- cused on the signs and symptoms of the subjects, evaluated before and aer treatment, in addition to visual acuity (VA) How to Cite this Article: and fundus oculi. Liu R, Wu X, Wang X, Gao J, Zhou J, Zhao Q. Effi- cacy of olopatadine hydrochloride 0.1%, emedastine di- Results: On day 8 (±1day)andday15(±2 days), all the fumarate 0.05%, and loteprednol etabonate 0.5% for antiallergic agents were found to be more effective than Chinese children with seasonal allergic conjunctivitis: a vehicle (p < 0.05) in terms of all the symptoms and signs. randomized vehicle-controlled study. Int Forum Allergy Rhinol. 2016;XX:XXX-XXX. llergic conjunctivitis (AC) is a common allergic disease dust mites,9,12 and animal dander1,12 are the most common A that is present on the eye. The most evident case is sea- sensitizing agents. sonal allergic conjunctivitis (SAC).1,2 Patients are often also It is well known that the main current topical med- affected by allergic rhinitis,3–6 asthma,1,3,5,6 eczema,3,5 and ications available for the treatment of SAC consist food or drug allergies. Their parents and grandparents usu- of corticosteroids, such as loteprednol etabonate (LE); ally suffer from atopic-related diseases.7 Plant pollen,1,8–11 H-1antagonists, such as emedastine; and dual action agents, such as olopatadine; or artificial tears (AT), such as car- boxymethylcellulose sodium. Department of Ophthalmology, the Second Hospital Affiliated to In the past, olopatadine hydrochloride 0.1% has Dalian Medical University, Dalian, China been compared with emedastine difumarate 0.05%,13 LE Correspondence to: Qi Zhao, MD, Department of Ophthalmology, the 14 15,16 Second Hospital Affiliated to Dalian Medical University. 467, Zhongshan Rd, 0.5%, and vehicle, respectively. In addition, compar- Dalian, 116023, Liaoning Province, China; e-mail:[email protected] isons have also been done between emedastine difumarate 13 Potential conflict of interest: None provided. 0.05% and the placebo and between LE 0.5% and the 17 Received: 12 April 2016; Revised: 6 September 2016; Accepted: placebo. However, emedastine difumarate 0.05% and 18 November 2016 LE 0.5% have not been compared with each other. On the DOI: 10.1002/alr.21882 View this article online at wileyonlinelibrary.com. basis of that, this study compares their efficacy and then 1 International Forum of Allergy & Rhinology, Vol. , No. , xxxx 2016 Liu et al. TABLE 1. The scoring system of eye symptoms* TABLE 2. The scoring system of eye signs* Score Severity Description Score Severity Description 0 Absent Without any symptoms 0 Absent Without any symptoms 1 Slight Slight symptoms, patients having little or 1 Mild Mild signs slight feeling 2 Moderate Moderate signs 2 Mild Mild symptoms, patients feeling discomfort 3 Severe Severe signs but being capable of tolerating 3 Moderate Moderate symptoms, patients being difficult *The main signs include conjunctival papilla, follicle, conjunctival congestion, edema. to tolerate 4 Severe Severe symptoms, patients being incapable of tolerating of symptoms (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The evaluation of grading is shown in Table 2. *The main symptoms include itching, photophobia, blinking. The measurement standard of the symptoms and signs was evaluated by the same investigator through the direct ques- respectively compares them with olopatadine 0.1%. We tioning of children or observation. All the efficacy variables mainly focus on comparing olopatadine, emedastine, LE, were assessed for both eyes at each visit. and vehicle (AT) in the temporary treatment of Chinese Exclusion criteria: aged ࣙ11 years or ࣘ4 years old. Chil- children with SAC in similar living environments. dren who suffered from refractive errors, those whose best corrected VA was ࣘ0.4, or those children who suffered from keratoconus were also excluded. In addition, those Patients and methods who had received an ocular operation or who wore intraoc- Study design ular lens or contact lenses were excluded. Outpatients with > This was a 3-visit, prospective, single-blind, randomized, intraocular pressure 21 mm Hg in any each eye were also placebo-controlled, single-center study in the Ophthalmol- excluded. Further exclusions were children using any antial- ogy Department of the Second Hospital affiliated with lergic medication (such as H-1 antihistamines, mast cell sta- Dalian Medical University. There were 90 subjects (180 bilizers, eye drops of corticosteroid, nasal spray, or general eyes) of SAC primarily in the study. We finally had 80 chil- drugs) in the 30 days before testing. Using any drugs that dren of 160 eyes (48 cases of boys, 32 girls, ranging from 5 cause eye diseases, any anti-allergic treatment, other ocular to 10 years old, with an average age of 6.33 ± 1.89 years); diseases and systemic diseases, other active eye diseases and another 10 cases were excluded due to loss to follow-up. diseases of the heart, brain, liver, kidney, or hematopoietic Registration of children with SAC took place from July system in the last 1 month also were disqualified in outpa- 2015 through November 2015 in our study. Before study tient selection. Those who were unable to assess the efficacy procedures were conducted, written informed consent was or failed to offer information completely were excluded. obtained from all parents/guardians. The study protocol Finally, those who were not using the ophthalmic solution was approved by the Ethics Committee of Second Hospital regularly, or not following-up, thus affecting the curative affiliated with Dalian Medical University. effect, were also excluded. Study subjects Study procedures The following were all the criteria of our study: the age The subjects were distributed into 4 groups by random of children ranging from 5 to 10 years old; stopping using number table; on average, 20 cases in each group. Children other anti-allergy agents for at least 30 days14; with grade were randomly assigned to receive topical administration 3 or higher in symptoms and grade 2 or higher in signs at of 1 drop of olopatadine hydrochloride (HCL) 0.1% oph- visit 1(the first study visit). All the variables with respect to thalmic solution (Patanol) twice per day (BID) (olopatadine baseline were similar in each group. Changes of symptoms solution group); 1 drop of emedastine difumarate 0.05% were graded on a 0 to 4 scale and increased by 0.5 incre- ophthalmic solution (Emadine) BID (emedastine solution ments; the higher the points the more evident the symp- group); LE 0.5% ophthalmic suspension (Lotemax) 4 times toms were. Ocular symptoms were graded on a 0 to 4 scale per day (QID) (LE solution group); or AT 0.5% (Refresh (0 = absent, 1 = slight, 2 = mild, 3 = moderate, and 4 Plus) 3 times per day (TID) (vehicle group); in both eyes for = severe).6 The main symptoms include itching, photopho- 14 ± 2 days. Ophthalmic solution was dropped into the bia, foreign body sensation, and blinking. The assessment fornix conjunctivae inferior for 1 drop in each eye. of grade is shown in Table 1. The main signs include papilla A visit 1 (day 0), on the first day of the study, all in upper and lower of palpebral conjunctiva, follicle, con- patients were questioned about ethnicity; systemic allergic junctival congestion, and conjunctival edema. Ocular signs conditions or not, and family members (father, mother, were graded on a 0 to 3 points, similar to the definition grandfather, grandmother, etc.) with atopic history International Forum of Allergy & Rhinology, Vol. , No. , xxxx 2016 2 Three treatments for SAC in Chinese children including suffering from allergic rhinitis, asthma, eczema, statistically significant (p < 0.05) between the study groups dermatitis, food allergy, and drug allergy. Moreover, they and the placebo group. There were no statistically signif- were asked whether, in their living environment, there icant differences among the treatment groups (p > 0.05).