***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE To evaluate the efficacy and safety of 0.18 % sodium hyaluronate ophthalmic solution ( Rejena , Vismed ) compared with its vehicle for the treatment of signs and symptoms of dry eye disease . DESIGN R and omized , placebo-controlled clinical trial . METHODS A total of 444 subjects with dry eye disease were r and omized 1:1 to active study drug ( n = 221 ) or vehicle control ( n = 223 ) in this multicenter , double-masked trial . Subjects instilled 1 to 2 drops , 3 to 6 times daily for 14 days , with evaluations at Days 7 and 14 . The study 's 2 primary efficacy endpoints were change from baseline at Day 7 in lissamine green staining scores ( objective ) and in global symptom frequency scores ( subjective ) . Results were analyzed using Wilcoxon rank sum test and Student t test in the intent-to-treat ( ITT ) population with last observation carried forward ( LOCF ) . RESULTS At Day 7 , the differences between the active and vehicle groups in change from baseline for lissamine green staining score ( P = .050 , Wilcoxon ; P = .029 , t test ) and global symptom frequency score ( P = .050 , Wilcoxon ; P = .017 , t test ) were both statistically significant . There were no clinical ly relevant safety findings related to the use of Rejena . CONCLUSIONS This study demonstrated the clinical efficacy of Rejena in the treatment of dry eye disease in both a primary objective endpoint and a primary subjective endpoint when compared to its vehicle . The study results also supported the well-known safety profile of Rejena Background Dry eye is a common condition , affecting approximately 10–20 % of the adult population . Artificial tears are often effective in relieving symptoms in mild and moderate dry eye by replenishing deficient tear volume . Sodium hyaluronate has been proposed as a component in artificial tears , due to its viscoelastic rheology . This paper reports on a study carried out to assess the efficacy of two recently developed eyedrops containing 0.1 % and 0.3 % sodium hyaluronate ( SH ) in the treatment of moderate dry eye . Methods Thirteen subjects were recruited with moderate dry eye . Forty microlitres of 0.1 % SH , 0.3 % SH , or 0.9 % saline were instilled in both eyes , and the subjects ’ symptom intensity and non-invasive break-up time ( NIBUT ) were measured at 5 , 15 , 30 , 45 , and 60 min , and then hourly , until 6 h after drop instillation . This was repeated twice following an interval of 7(±1 ) days , but with a different treatment so that at the end of the final visit each subject had trialled all products . Drop allocation was r and omized and double-masked . Results Both symptoms and NIBUT improved with all treatments . These changes were of a larger magnitude and longer duration with the SH containing eyedrops than with saline . SH of 0.3 % tended to perform better than 0.1 % SH and achieved statistical significance ( P=0.04 ) for NIBUT when considered over the whole 6-h study period . Conclusions Sodium hyaluronate of 0.1 % and 0.3 % reduces symptoms of ocular irritation and lengthens NIBUT in subjects with moderate dry eye more effectively than saline , in terms of peak effect and duration of action BACKGROUND / AIMS Hyaluronan ( sodium hyaluronate ) has been shown to confer objective and subjective improvement in patients with dry eye syndrome . This study compared the efficacy and safety of a 0.1 % solution of hyaluronan with 0.9 % saline , when administered topically to the eye , in the treatment of symptoms of severe dry eye syndrome . METHODS A r and omised , double blind , crossover clinical trial in which subjects were r and omised to receive either hyaluronan or saline , applied as one or two drops to the eye , three or four times a day or as required . After 28 days ’ treatment , subjects crossed over to the other study medication for a further 28 days ’ treatment . RESULTS 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer ’s score ( p=0.0006 ) and rose bengal staining score ( p=0.0001 ) were observed during treatment with hyaluronan . In a subjective assessment of the effectiveness of two treatments , a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness ( p<0.001 ) . No adverse events attributable to hyaluronan treatment were reported . CONCLUSION The study demonstrates a clear benefit of hyaluronan over saline , in both subjective and objective assessment s of dry eye syndrome . Hyaluronan was shown to be well tolerated Aims To assess the safety and performance of a 0.1 % ( w/v ) solution of sodium hyaluronate ( HA , Fermavisc ® , in the alleviation of symptoms of severe dry eye in comparison with a 1.4 % ( w/v ) solution of polyvinyl alcohol . Methods A r and omised , crossover , multicentre study carried out at eight centres in the UK . Eligible patients giving written informed consent were r and omised to the order in which they would receive the two study products . Each treatment period lasted for 4 weeks , then the patient crossed over to the other study product . Symptoms of burning and grittiness were assessed by visual analogue scale ( VAS ) at each study visit and other objective clinical assessment s of ocular structure and function were carried out at baseline and the end of each treatment period . Results Thirty-nine patients were entered into the study and 32 completed both treatment periods and were included in the statistical analyses . A significant improvement in the patients ’ VAS assessment of burning was seen after treatment with HA ( P = 0.03 , 95 % Confidence Interval : −23.5 to −1.1 ) . This treatment also result ed in a significantly lower rose bengal staining score ( P = 0.04 , 95 % Confidence Interval : −1.62 to −0.05 for the right eye ) . Conclusion The results show a significant clinical benefit in terms of relief of the symptom of burning when HA is applied topically to the eye three or four times per day or as required . HA also appears to have a protective effect on the corneal epithelium , as shown by a reduction in the level of staining of corneal epithelial cells by rose bengal . This study confirms that Fermavisc ® is a safe and effective product for use in the alleviation of symptoms of severe dry eye syndrome Background The ocular surface changes of keratoconjunctivitis sicca ( KCS ) could be the result of the effect of an altered tear film on the epithelial environment . Purpose To evaluate the possibility of improving the environmental conditions of the ocular surface by lowering tear osmolarity , increasing tear film volume and stabilising the tear film . Also , to study the effect of such an improvement on the epithelial cells of the ocular surface . Methods One hundred and thirty-five patients with a diagnosis of KCS were treated on a r and omised basis with either unpreserved hypotonic 0.4 % hyaluronic acid ( HHA ) eye drops or 0.3 % hydroxypropylmethylcellulose plus 0.1 % Dextran 70 ( HPMC ) eye drops 6 times a day for 60 or 90 days . In all patients a Schirmer I test , break-up time ( BUT ) , ocular surface staining with 1 % Bengal Rose , or 2 % fluorescein , as well as subjective symptoms , were recorded before and 15 , 30 and 60 days after the beginning of the study . Patients were divided into three subgroups and the effect of the treatment was studied using three different techniques : the tear ferning test , conjunctival impression cytology and tear osmolarity measurement . Results Improvements in BUT , vital staining , Schirmer I and symptoms were recorded in both groups of treatment , with significant differences for patients treated with 0.4 % HHA . On day 60 , 30 min after installation : tear ferning patterns changed from 100 % pathological ( types III – IV ) to 93 % physiological ( types I – II ) in the 0.4 % HHA group and from 100 % pathological to 78 % physiological in the 0.3 % HPMC group ( p < 0.01 between groups ) . Tear osmolarity shifted from 353 ± 23 to 305 ± 6 mosmolA in the 0 - 4 % HHA group and from 346 ± 15 to 336 ± 8 mosmol/l in the 0.3 % HPMC group ( p < 0.001 between groups ) . On day 90 , the impression cytology score improved from 1.2 to 1.9 in the 0.4 % HHA group while it did not change in the 0.3 % HPMC group ( p < 0.05 between groups ) . Conclusion In KCS appropriate treatment with a hypotonic 0.4 % HHA tear substitute can change the tear environment and results in improvement of the epithelial conditions of the ocular surface This study assessed the repeatability of various methods of measuring tear break-up time ( TBUT ) with and without soft contact lenses ( CLs ) .  TBUT was measured on 22 subjects with the tearscope , videokeratoscope and slit-lamp before and after  30 min of soft CL wear  , and immediately after  CL removal .  Slit-lamp corneal TBUT was measured with fluorescein and without fluorescein while wearing CLs .  TBUT was measured three times on the right eye only , using each technique in r and omised order . TBUT measurements on CLs were repeated a second day . TBUT measurements were highly variable under all conditions and our results indicated a lack of correlation between techniques . The videokeratoscope was the least repeatable ; while the tearscope was the most repeatable technique Between mid-May and mid-July 1987 we performed a prospect i ve crossover study of two unit-dose preservative-free artificial tear solutions , 1.4 % polyvinyl alcohol ( Refresh ) and 0.1 % sodium hyaluronate ( Hylorin ) in 14 female patients with severe dry eye syndrome . The patients were examined before treatment and after each of two trials with both products . A significant reduction in the mean score for dry-eye-induced keratitis ( p = 0.001 ) and for mucous str and s ( p = 0.03 ) was observed following the second of two trials with sodium hyaluronate . A significant reduction in the mean score for burning and irritation was observed with both solutions ( p = 0.009 ) . We believe that the elimination of preservatives from artificial tear preparations may substantially reduce the iatrogenic effects of these frequently applied medications Clinical trials to evaluate the effectiveness of therapy for dry eye disease are challenging because of the nature of the disease , the multiple palliative methods used by patients to control their symptoms , and the potential limitations of the techniques available to evaluate therapeutic outcomes . This review identifies some of the pitfalls encountered in recent clinical trials in dry eye disease . The peculiarities of dry eye disease with respect to symptoms , signs , and patho- physiological changes are discussed . Potential problems that apply to all clinical trials , including patient selection , r and omization in small population s , and assessment of the placebo effect , are presented with respect to dry eye clinical trials . Considerations regarding study design address inclusion /exclusion criteria and selection of outcome measures . Special attention is given to methods of symptom analysis , techniques of staining of the ocular surface , and grading systems for surface staining . Alternative methods to the st and ard clinical trial are mentioned to place them in perspective for overall evaluation of dry eye disease therapy . Finally , caveats are provided to encourage investigators to vigorously conduct future clinical trials in dry eye therapy Purpose : To compare the effects of Viscofresh 0.5 % ( carmellose sodium 0 . 5 % ) versus Lubristil ( sodium hyaluronate 0.15 % ) in dry eye syndrome and to study the influence of these two treatments on the expression of various inflammatory markers by flow cytometry in impression cytology specimens . Methods : In this r and omized , masked-observer , parallel group , single-center study , 15 patients with dry eye syndrome were r and omized to sodium carmellose 0.5 % or sodium hyaluronate 0.15 % 1-month treatment after a 1-week washout period .  Corneal staining with flurescein , breakup time , Schirmer 1 test with anesthesia ( Jones test ) , and tear clearance were assessed . Besides , conjunctival impression cytology was performed to investigate inflammatory markers ( CD3 , CD11b , and HLA-DR ) using flow cytometry . Results : Carmellose group shows statistical improvement compared with the hyaluronate group in breakup time , corneal staining , and HLA-DR . The two other inflammatory markers had also a tendency for a decreased expression in both groups , with no statistical significance . There were neither visual acuity loss nor other complications related to treatment . Conclusion : Both artificial tears improve dry eye signs and symptoms and inflammatory markers expression , with significant better results in carmellose group Background / aims : Several studies have reported that sodium hyaluronate is able to improve both symptoms and signs in patients with dry eye but none have demonstrated an improvement of conjunctival epithelial cell abnormalities of the ocular surface . The aim of this study was to explore the effect of sodium hyaluronate-containing eye drops on the ocular surface of patients with dry eye during long term treatment . Methods : A r and omised double blind study was undertaken in 86 patients with medium to severe dry eye ( that is , rose beng 
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In summary , neither preparation was shown to be consistently superior across all outcome measures .
The difference in effect between preparations on SH and TBUT was not clinical ly significant