we finally had 80 children of 160 eyes ( 48 cases of boys , 32 girls , ranging from 5 to 10 years old , with an average age of 6.33  1.89 years ) ; another 10 cases were excluded due to loss to followup . registration of children with sac took place from july 2015 through november 2015 in our study . before study procedures were conducted , written informed consent the study protocol was approved by the ethics committee of second hospital affiliated with dalian medical university . the following were all the criteria of our study : the age of children ranging from 5 to 10 years old ; stopping using other antiallergy agents for at least 30 days14 ; with grade 3 or higher in symptoms and grade 2 or higher in signs at visit 1(the first study visit ) . all the variables with respect to baseline were similar in each group . changes of symptoms were graded on a 0 to 4 scale and increased by 0.5 increments ; the higher the points the more evident the symptoms were . ocular symptoms were graded on a 0 to 4 scale ( 0 = absent , 1 = slight , 2 = mild , 3 = moderate , and 4 = severe).6 the main symptoms include itching , photophobia , foreign body sensation , and blinking . the main signs include papilla in upper and lower of palpebral conjunctiva , follicle , conjunctival congestion , and conjunctival edema . ocular signs were graded on a 0 to 3 points , similar to the definition of symptoms ( 0 = absent , 1 = mild , 2 = moderate , and 3 = severe ) . the measurement standard of the symptoms and signs was evaluated by the same investigator through the direct questioning of children or observation . the scoring system of eye symptoms * 
  * the main symptoms include itching , photophobia , blinking . the scoring system of eye signs * 
  * the main signs include conjunctival papilla , follicle , conjunctival congestion , edema . exclusion criteria : aged 11 years or 4 years old . children who suffered from refractive errors , those whose best corrected in addition , those who had received an ocular operation or who wore intraocular lens or contact lenses were excluded . outpatients with intraocular pressure > 21 mm hg in any each eye were also excluded . further exclusions were children using any antiallergic medication ( such as h1 antihistamines , mast cell stabilizers , eye drops of corticosteroid , nasal spray , or general drugs ) in the 30 days before testing . using any drugs that cause eye diseases , any antiallergic treatment , other ocular diseases and systemic diseases , other active eye diseases and diseases of the heart , brain , liver , kidney , or hematopoietic system in the last 1 month also were disqualified in outpatient selection . those who were unable to assess the efficacy or failed to offer information completely were excluded . finally , those who were not using the ophthalmic solution regularly , or not followingup , thus affecting the curative effect , were also excluded . the subjects were distributed into 4 groups by random number table ; on average , 20 cases in each group . children were randomly assigned to receive topical administration of 1 drop of olopatadine hydrochloride ( hcl ) 0.1% ophthalmic solution ( patanol ) twice per day ( bid ) ( olopatadine solution group ) ; 1 drop of emedastine difumarate 0.05% ophthalmic solution ( emadine ) bid ( emedastine solution group ) ; le 0.5% ophthalmic suspension ( lotemax ) 4 times per day ( qid ) ( le solution group ) ; or at 0.5% ( refresh plus ) 3 times per day ( tid ) ( vehicle group ) ; in both eyes for 14  2 days . ophthalmic solution was dropped into the fornix conjunctivae inferior for 1 drop in each eye . a visit 1 ( day 0 ) , on the first day of the study , all patients were questioned about ethnicity ; systemic allergic conditions or not , and family members ( father , mother , grandfather , grandmother , etc . ) with atopic history including suffering from allergic rhinitis , asthma , eczema , dermatitis , food allergy , and drug allergy . moreover , they were asked whether , in their living environment , there were pets or not ; and whether they had done allergen detection ( especially plant , pollen , dust mites , and animal dander ) in the past or not . furthermore , naked va and the best corrected va were measured carefully , va was observed through the international standard e vision table and all the children used the same va chart . the investigator was blinded to what ophthalmic solution the children were taking upon their treatment . ocular symptoms and signs , va , and fundus preset lens examination was also collected during visit 2 ( day 7  1 ) and visit 3 ( day 14  2 ) . the spss 21.0 software program ( ibm corp . , armonk , ny ) was used to perform the statistical analysis . the symptoms and signs of objects were consistent with homogeneity of variance by levene test . data were summarized and presented as the number of collection , percentages , mean and standard deviation ( sd ) . the variables of symptoms and signs from baseline were used in this randomized and vehiclecontrolled study , analysis of covariance ( ancova ) model with double side test . they were expressed as mean , sd , 95% confidence interval ( ci ) , and p value . this was a 3visit , prospective , singleblind , randomized , placebocontrolled , singlecenter study in the ophthalmology department of the second hospital affiliated with dalian medical university . we finally had 80 children of 160 eyes ( 48 cases of boys , 32 girls , ranging from 5 to 10 years old , with an average age of 6.33  1.89 years ) ; another 10 cases were excluded due to loss to followup . registration of children with sac took place from july 2015 through november 2015 in our study . before study procedures were conducted , written informed consent the study protocol was approved by the ethics committee of second hospital affiliated with dalian medical university . the following were all the criteria of our study : the age of children ranging from 5 to 10 years old ; stopping using other antiallergy agents for at least 30 days14 ; with grade 3 or higher in symptoms and grade 2 or higher in signs at visit 1(the first study visit ) . all the variables with respect to baseline were similar in each group . changes of symptoms were graded on a 0 to 4 scale and increased by 0.5 increments ; the higher the points the more evident the symptoms were . ocular symptoms were graded on a 0 to 4 scale ( 0 = absent , 1 = slight , 2 = mild , 3 = moderate , and 4 = severe).6 the main symptoms include itching , photophobia , foreign body sensation , and blinking . the main signs include papilla in upper and lower of palpebral conjunctiva , follicle , conjunctival congestion , and conjunctival edema . ocular signs were graded on a 0 to 3 points , similar to the definition of symptoms ( 0 = absent , 1 = mild , 2 = moderate , and 3 = severe ) . the measurement standard of the symptoms and signs was evaluated by the same investigator through the direct questioning of children or observation . the scoring system of eye symptoms * 
  * the main symptoms include itching , photophobia , blinking . the scoring system of eye signs * 
  * the main signs include conjunctival papilla , follicle , conjunctival congestion , edema . children 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 who had received an ocular operation or who wore intraocular lens or contact lenses were excluded . outpatients with intraocular pressure > 21 mm hg in any each eye were also excluded . further exclusions were children using any antiallergic medication ( such as h1 antihistamines , mast cell stabilizers , eye drops of corticosteroid , nasal spray , or general drugs ) in the 30 days before testing . using any drugs that cause eye diseases , any antiallergic treatment , other ocular diseases and systemic diseases , other active eye diseases and diseases of the heart , brain , liver , kidney , or hematopoietic system in the last 1 month also were disqualified in outpatient selection . those who were unable to assess the efficacy or failed to offer information completely were excluded . finally , those who were not using the ophthalmic solution regularly , or not followingup , thus affecting the curative effect , were also excluded . the subjects were distributed into 4 groups by random number table ; on average , 20 cases in each group . children were randomly assigned to receive topical administration of 1 drop of olopatadine hydrochloride ( hcl ) 0.1% ophthalmic solution ( patanol ) twice per day ( bid ) ( olopatadine solution group ) ; 1 drop of emedastine difumarate 0.05% ophthalmic solution ( emadine ) bid ( emedastine solution group ) ; le 0.5% ophthalmic suspension ( lotemax ) 4 times per day ( qid ) ( le solution group ) ; or at 0.5% ( refresh plus ) 3 times per day ( tid ) ( vehicle group ) ; in both eyes for 14  2 days . ophthalmic solution was dropped into the fornix conjunctivae inferior for 1 drop in each eye . a visit 1 ( day 0 ) , on the first day of the study , all patients were questioned about ethnicity ; systemic allergic conditions or not , and family members ( father , mother , grandfather , grandmother , etc . ) with atopic history including suffering from allergic rhinitis , asthma , eczema , dermatitis , food allergy , and drug allergy . moreover , they were asked whether , in their living environment , there were pets or not ; and whether they had done allergen detection ( especially plant , pollen , dust mites , and animal dander ) in the past or not . furthermore , naked va and the best corrected va were measured carefully , va was observed through the international standard e vision table and all the children used the same va chart . the investigator was blinded to what ophthalmic solution the children were taking upon their treatment . ocular symptoms and signs , va , and fundus preset lens examination was also collected during visit 2 ( day 7  1 ) and visit 3 ( day 14  2 ) . the spss 21.0 software program ( ibm corp . , armonk , ny ) was used to perform the statistical analysis . the symptoms and signs of objects were consistent with homogeneity of variance by levene test . data were summarized and presented as the number of collection , percentages , mean and standard deviation ( sd ) . the variables of symptoms and signs from baseline were used in this randomized and vehiclecontrolled study , analysis of covariance ( ancova ) model with double side test . they were expressed as mean , sd , 95% confidence interval ( ci ) , and p value . for the olopatadine group , the mean age of the children was 6.35  2.01 years and 65% were boys . in the emedastine group , the mean age of children in the le group was 6.40  1.99 years , 50% of whom were boys ; the mean age of the children from the vehicle group was 6.33  1.80 years , 55% of whom were boys . the general characteristics of children between the treatment groups and the control group were wellbalanced ( table 3 ) . demographic characteristics of the study population ac = allergic conjunctivitis ; sd = standard deviation . table 4 shows the changes of ocular symptoms from baseline of the drug groups compared with those of the placebo group after 2 weeks of treatment . after 1 week , changes in ocular itching , blinking of eyes , and photophobia were statistically significant ( p < 0.05 ) between the study groups and the placebo group . there were no statistically significant differences among the treatment groups ( p > 0.05 ) . after 2 weeks of treatment , the changes in ocular itching , blinking of eyes , and photophobia were statistically significant between the study groups and the vehicle group ( p < 0.05 ) , and there were no statistically significant differences among the treatment groups ( p > 0.05 ) . the ocular symptoms changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . table 5 expresses the grades of sac for all the tests in ocular signs after 2 weeks of treatment . for all the signs , there were no statistically significant differences among the treatment groups ( p > 0.05 ) , and the differences between the treatment groups and the control group were statistically significant ( p < 0.05 ) . the ocular signs changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . no clinically significant changes were found in va from the baseline and no changes were found in fundus oculi among all the groups in each observation . for the olopatadine group , the mean age of the children was 6.35  2.01 years and 65% were boys . in the emedastine group , the mean age of children in the le group was 6.40  1.99 years , 50% of whom were boys ; the mean age of the children from the vehicle group was 6.33  1.80 years , 55% of whom were boys . the general characteristics of children between the treatment groups and the control group were wellbalanced ( table 3 ) . demographic characteristics of the study population ac = allergic conjunctivitis ; sd = standard deviation . table 4 shows the changes of ocular symptoms from baseline of the drug groups compared with those of the placebo group after 2 weeks of treatment . after 1 week , changes in ocular itching , blinking of eyes , and photophobia were statistically significant ( p < 0.05 ) between the study groups and the placebo group . there were no statistically significant differences among the treatment groups ( p > 0.05 ) . after 2 weeks of treatment , the changes in ocular itching , blinking of eyes , and photophobia were statistically significant between the study groups and the vehicle group ( p < 0.05 ) , and there were no statistically significant differences among the treatment groups ( p > 0.05 ) . the ocular symptoms changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . table 5 expresses the grades of sac for all the tests in ocular signs after 2 weeks of treatment . for all the signs , there were no statistically significant differences among the treatment groups ( p > 0.05 ) , and the differences between the treatment groups and the control group were statistically significant ( p < 0.05 ) . the ocular signs changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . table 4 shows the changes of ocular symptoms from baseline of the drug groups compared with those of the placebo group after 2 weeks of treatment . after 1 week , changes in ocular itching , blinking of eyes , and photophobia were statistically significant ( p < 0.05 ) between the study groups and the placebo group . there were no statistically significant differences among the treatment groups ( p > 0.05 ) . after 2 weeks of treatment , the changes in ocular itching , blinking of eyes , and photophobia were statistically significant between the study groups and the vehicle group ( p < 0.05 ) , and there were no statistically significant differences among the treatment groups ( p > 0.05 ) . the ocular symptoms changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . table 5 expresses the grades of sac for all the tests in ocular signs after 2 weeks of treatment . for all the signs , there were no statistically significant differences among the treatment groups ( p > 0.05 ) , and the differences between the treatment groups and the control group were statistically significant ( p < 0.05 ) . the ocular signs changing from baseline after 2 weeks of treatment ( based on the uniform diagnostic criteria ) * 
  * values are mean  sd or p ( 95% ci ) , as indicated . no clinically significant changes were found in va from the baseline and no changes were found in fundus oculi among all the groups in each observation . for patients who suffer from ocular discomfort , with ac , their quality of life is affected19 to a certain degree and their families may be economically burdened.20 as for children , when visiting doctors , the parents sometimes mistakenly assume that their children have hyperkinetic , to some extent , which can affect the physical and mental health of children.21 so it is essential to explore a safe , effective , shortterm , and proper therapeutic drug to manage the ac.22 
  the novelty of the present trial lies in that it is the first time the efficacy of olopatadine hydrochloride 0.1% , emedastine difumarate 0.05% , and le 0.5% ophthalmic suspension has been compared among the 3 drugs . to the best of our knowledge , olopatadine hydrochloride 0.1% has been compared to emedastine difumarate 0.05%,13 le 0.5% ophthalmic suspension,14 and placebo15 , 16 , 22 , 23 , 24 with each other , respectively , in efficacy . emedastine difumarate 0.05% has been compared with vehicle to assess efficacy.13 in addition , le 0.5% ophthalmic suspension has been compared with placebo to evaluate efficacy.17 however , emedastine difumarate 0.05% and le 0.5% ophthalmic suspension have not been compared with each other , while on that basis we put forward with these 2 eye drops compared to olopatadine hydrochloride 0.1% , respectively . after the treatment , ocular signs and symptoms that appeared in our study may be related to the following reasons : ( 1 ) in this trial the control group was at , some of which offered alleviation through lubricating the ocular surface and raised humidity or glutinosity factors to salt solution25 ; ( 2 ) at may improve the barrier function of the ocular surface,26 which is useful in the treatment of sac27 ; ( 3 ) compliance of guardians / parents and children was good  they very strictly used the ophthalmic solution according to the requirements . hence the efficacy of the treatment came out . in the current study , compared with emedastine difumarate 0.05% , olopatadine hydrochloride 0.1% did not show a statistically significant difference ( p > 0.05 ) in suppressing the symptoms and signs of sac and it was consistent with the conclusion obtained by borazan et  al.13 
  olopatadine hydrochloride 0.1% solution displayed no obvious superiority when compared to le 0.5% ophthalmic suspension , which was in agreement with gong et  al.,14 who reported that le ophthalmic suspension 0.5% compared with olopatadine hydrochloride 0.1% was inferior in 300 patients . on the contrary , berdy et  al.28 reported that olopatadine hydrochloride 0.1% was superior to le hydrochloride 0.5% in the alleviation of ocular itch and ocular hyperemia . in relief of the symptoms and signs of sac , olopatadine hydrochloride 0.1% ophthalmic solution compared with vehicle , the difference was statistically significant ( p < 0.05 ) . our study was consistent with that of mclaurin et  al.23 and mah et  al.,29 who reported how olopatadine hydrochloride 0.1% ophthalmic solution compared with placebo . in their reports , olopatadine hydrochloride 0.1% ophthalmic solution was more effective in reducing ocular symptoms and signs of patients suffering from ac . the results of olopatadine hydrochloride 0.1% ophthalmic solution compared with placebo may be that the control agent was at , though it may water down the allergen from eyes and serve as a barrier to additional exposure by keeping the allergen from adhesion to the ocular surface,30 whereas olopatadine hydrochloride 0.1% is a dualaction agent . in the current study , emedastine difumarate 0.05% was superior to vehicle in releasing the symptoms and signs of sac and the differences were significant ( p < 0.05 ) . in a previous study , borazan et  al.13 compared the efficacy of emedastine difumarate 0.05% with placebo and highlighted that emedastine difumarate 0.05% was more effective than placebo in offering rapid relief to patients with sac . as for the comparison of le hydrochloride 0.5% and vehicle , le hydrochloride 0.5% has been demonstrated to be more effective than placebo in the treatment of sac in an earlier study.30 
  in the present study , emedastine difumarate 0.05% was equally effective with le hydrochloride 0.5% ( p > 0.05 ) in suppressing the clinical symptoms and signs of sac . since this was the first time comparing them with each other , the sample size was small , with only 20 cases in each group , and the study was confined to children 5 to 10 years old , it was confirmed that emedastine and le had no statistically significant difference in a small sample caseseries research study . the reasons of the study are as follows : olopatadine hydrochloride 0.1% is a dualaction agent ; emedastine difumarate 0.05% is a h1 receptor antagonist ; le suspension 0.5% is a new c20 ester drug , transforming into inactive metabolites , in this case the side effect is small30 ; and at may water down the allergen from eyes and serve as a barrier for additional exposure through keeping the allergen from adhering to the ocular surface.27 in addition , the observation in the study lasts 2 weeks , which is relatively short . it is still required a longterm observation to provide a new theoretical support in the clinical study to make more patients to alleviate the pain suffering from sac . we have not performed conjunctival impression cytology in the study , which is a limitation of our research . conjunctival cytology may find eosinophils , basophils , as well as mast cells , while it will receive negative results inevitably . on the other hand , we also take the tolerability and acceptance of children and guardians into consideration . in particular , the subjects are 5 to 10 years old , which makes it inevitable for them to have fears . among the 80patient case study we conducted , our conclusion was relatively limited to the drug use of children ; besides , the compliance of children is usually poor . it confirmed that olopatadine , emedastine , and le were equally effective only in a small sample of children . as far as we all know , this is the first time in the comparison of three drugs , so it is still necessary for a longterm observation in a further large sample with antiallergic drugs , and taking the adults as the subjects should be performed in the further clinical studies to certificate and validate this research . in summary , the efficacy of olopatadine hydrochloride 0.1% , emedastine difumarate 0.05% , and le suspension 0.5% was equal , and olopatadine hydrochloride 0.1% , emedastine difumarate 0.05% , and le suspension 0.5% were more effective than vehicle . we expect the present study will be beneficial to clinical research and will be illuminating for ophthalmologists when selecting an appropriate ophthalmic solution in sac .
backgroundallergic conjunctivitis ( ac ) is a disease of various agents that affects the physical and mental health of children . 
 although the most effective therapy has not been found so far , it is essential to explore the considerable therapeutic method . 
 we compared the clinical efficacy of olopatadine , emedastine , loteprednol etabonate ( le ) , and vehicle for treating seasonal allergic conjunctivitis ( sac ) in chinese children.methodseighty cases of 160 eyes aged from 5 to 10 years with sac were available and those subjects were randomly distributed into 4 groups . 
 both their eyes received olopatadine hydrochloride 0.1% twice a day , emedastine difumarate 0.05% twice a day , or le 0.5% 4 times a day , respectively , whereas those of the control group received artificial tears ( at ) 0.5% 3 times a day . 
 this study was conducted successfully and the observations were collected before treatment and on day 8 ( 1 day ) and day 15 ( 2 days ) afterward . the principal measurement of efficacy was focused on the signs and symptoms of the subjects , evaluated before and after treatment , in addition to visual acuity ( va ) and fundus oculi.resultson day 8 ( 1 day ) and day 15 ( 2 days ) , all the antiallergic agents were found to be more effective than vehicle ( p < 0.05 ) in terms of all the symptoms and signs . 
 however , there was no statistical significance ( p  0.05 ) shown among the treatment groups . 
 there were no evident changes in va and no clinically significant changes were observed in fundus oculi.conclusionafter the treatment , the efficacy presented a similar distribution among the trial groups .