***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 and compare corneal staining patterns of lissamine green ( LG ) versus rose bengal ( RB ) in patients with dry eye syndrome . Secondary objectives included addressing patient 's comfort after instillation and to correlate disease severity with staining patterns . Methods : R and omized , comparative , crossover series . Patients with previous diagnosis of mild to moderate dry eye syndrome were divided in 2 groups regarding dye instillation order ( group A : RB first ; group B : LG first ) . Both dyes were applied in regular intervals , and a staining score ( van Bijsterveld scale ) was used to correlate and compare the results . Disease severity was determined by the Ocular Surface Disease Index . Comfort was evaluated by patient 's answer in an objective question naire . Results : Sixty eyes of 30 consecutive patients ( 24 females and 6 males ) were included . There was no statistical difference between groups regarding disease severity , sex , or age . LG and RB showed good clinical correlation in both groups ( group A : r = 0.939 , P < 0.001 ; group B : r = 0.915 , P < 0.001 ) . LG was better tolerated than RB ( P = 0.003 in both groups ) . Overall , we found a low statistical correlation between disease severity and staining scores . Conclusions : Both LG and RB showed similar staining patterns .  RB was found to provide greater patient discomfort . There was no correlation between disease severity ( addressed by the ocular surface disease index question naire ) and staining patterns ( measured by the van Bijsterveld scale ) OBJECTIVE To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practice s and a reference sample of persons without eye disease . SETTING Eleven university-based ophthalmology practice s and the NEI Clinical Center . PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Seven of the 12 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to create the NEI VFQ-25  , all subjects completed an interview that included the 51-item NEI VFQ . Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable . The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure , observed between-group differences in scores for persons with different eye diseases of varying severity , and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity . CONCLUSIONS The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey . This shorter version will be more feasible in setting s such as clinical trials where interview length is a critical consideration . In addition , preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied ; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity Aim To investigate the association between dry eye symptoms and depression in an adult population . Methods In this population -based cross-sectional study , a r and om sample of 1957 subjects from the Beijing Eye Study was examined for dry eye disease ( DED ) in 2006 . All patients completed an interviewer-assisted question naire on dry eye symptoms and underwent measurement of tear break-up time ( TBUT ) , slit-lamp evaluation of corneal staining and meibomian gl and dysfunction ( MGD ) , and the Schirmer test .  In 2011 , 1456 subjects from this sample were evaluated for depression using a depression scale . The association between depression symptoms and dry eye clinical tests was evaluated . Results Definite depression was more prevalent in patients with DED than in subjects without DED ( 13.7±0.4 % vs 8.6±0.3 % , p=0.02 ) . The depression score was correlated with dry eye symptoms ( correlation coefficient r=0.07 ; p=0.013 ) but not with TBUT ( p=0.18 ) , the Schirmer test ( p=0.37 ) , corneal staining ( p=0.30 ) and MGD evaluation ( p=0.93 ) . In multivariate regression analysis , the risk of definite depression remained significantly associated with dry eye symptoms ( p=0.028 ) after adjusting for lower cognitive status ( p=0.01 ) , rural region of habitation ( p=0.023 ) and lower body weight ( p=0.05 ) . Conclusions In an older population from Beijing , depression was associated with DED and in particular with dry eye symptoms PURPOSE To evaluate mRNA levels of the ocular mucins MUC1 , MUC2 , MUC4 , MUC5AC , and MUC7 in conjunctival impression cytology sample s from patients with moderate to severe dry eye syndrome ( DES ) compared with a population of healthy subjects ; and to investigate the use of the levels of these mucin genes as biomarkers of DES and subsequently as a potential diagnostic test for DES . METHODS This prospect i ve study commenced in the year 2000 and ended in the year 2009 . Thirty-eight patients with DES and 43 age- and sex-matched healthy subjects completed the initial part of the study . Investigations were repeated at a later stage in 16 healthy subjects and 30 patients with DES , which were used as external validation data . Conjunctival impression cytology was performed in all subjects to test gene expression of ocular mucin genes MUC1 , MUC2 , MUC4 , MUC5AC , and MUC7 . Statistical analysis was performed to determine whether there was a difference in the levels of mucin gene expression between the two groups of subjects . Sensitivity and specificity of mucin gene expression for the diagnosis of DES was calculated . RESULTS Expressions of MUC1 , MUC2 , MUC4 , and MUC5AC ( P < 0.0001 ) were significantly lower in conjunctival epithelium of patients with DES compared with that in normal subjects . These results were replicated in the external control subject and patient groups . MUC1 expression levels demonstrated the greatest sensitivity ( 83.3 % ) and specificity ( 87.5 % ) among all genes tested . CONCLUSIONS The data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials PURPOSE To evaluate the use of tear osmolarity in the diagnosis of dry eye disease . DESIGN A prospect i ve , observational case series to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose dry eye disease . METHODS A multicenter , 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age .  Bilateral tear osmolarity , tear film break-up time ( TBUT ) , corneal staining , conjunctival staining , Schirmer test  , and meibomian gl and grading were performed . Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal , mild or moderate , or severe dry eye . The main outcome measures were sensitivity , specificity , area under the receiver operating characteristic curve , and intereye variability . RESULTS Of the 6 tests , tear osmolarity was found to have superior diagnostic performance . The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L , whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L , tear hyperosmolarity exhibited 73 % sensitivity and 92 % specificity . By contrast , the other common tests exhibited either poor sensitivity ( corneal staining , 54 % ; conjunctival staining , 60 % ; meibomian gl and grading , 61 % ) or poor specificity ( tear film break-up time , 45 % ; Schirmer test , 51 % ) .  Tear osmolarity also had the highest area under the receiver operating characteristic curve ( 0.89 ) . Intereye differences in osmolarity were found to correlate with increasing disease severity ( r(2 ) = 0.32 ) . CONCLUSIONS Tear osmolarity is the best single metric both to diagnose and classify dry eye disease . Intereye variability is a characteristic of dry eye not seen in normal subjects PURPOSE A prospect i ve , multisite clinical study ( 10 sites in the European Union and the United States ) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity . METHODS Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population , 299 of which qualified with complete data sets .  Osmolarity testing , Schirmer test without anesthesia , tear film breakup time ( TBUT ) , corneal staining , meibomian dysfunction assessment , and conjunctival staining  were performed bilaterally . A symptom question naire , the Ocular Surface Disease Index ( OSDI ) , was also administered to each patient . Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated . RESULTS Osmolarity was found to have the highest correlation coefficient to disease severity ( r(2 ) = 0.55 ) , followed by conjunctival staining ( r(2 ) = 0.47 ) , corneal staining ( r(2 ) = 0.43 ) , OSDI ( r(2 ) = 0.41 ) , meibomian score ( r(2 ) = 0.37 ) , TBUT ( r(2 ) = 0.30 ) , and Schirmer result ( r(2 ) = 0.17 ) . A comparison of st and ard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospect ively defined normal and dry eye groups . Fully 63 % of the subjects were found to be poorly classified by combinations of clinical thresholds . CONCLUSIONS Tear film osmolarity was found to be the single best marker of disease severity across normal , mild/moderate , and severe categories . Other tests were found to be informative in the more severe forms of disease ; thus , clinical judgment remains an important element in the clinical assessment of dry eye severity . The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs . ( Clinical Trials.gov number , NCT00848198 . ) Purpose : To measure the correlation between subjective symptom score , conventional clinical tests , and Fourier-domain optical coherence tomography ( FD-OCT ) of lower tear meniscus parameters in patients with dry eye disease . Methods : Eighteen patients with dry eye disease requiring medical therapy and /or punctal occlusion were recruited for this prospect i ve , nonr and omized , observational case series . Severity of symptoms of dry eye disease was assessed using the Indiana University Dry Eye Question naire 2002 . Clinical assessment s were completed using slit-lamp biomicroscopy , rose bengal dye staining , fluorescein tear breakup time ( TBUT ) , and a 5-minute Schirmer test with topical anesthesia . The lower tear meniscus was imaged using an FD-OCT system with 5-&mgr;m axial resolution and measured manually by a masked grade r using computer calipers . Correlation was assessed using Spearman correlation coefficient ( & rgr ; ) . Results : The mean ( ±SD ) scaled symptom score was 58 ± 21 , with a range of 0 to 100 . Vital staining test averaged 1.7 ± 3.4 , TBUT averaged 4.4 ± 1.8 seconds , and Schirmer tests averaged 10.2 ± 8.1 mm . As determined by optical coherence tomography , the meniscus height was 228 ± 153 & mgr;m , depth was 127 ± 79 & mgr;m , and cross-sectional area was 0.018 ± 0.021 mm2 . Optical coherence tomography meniscus area was negatively correlated with the symptom question naire score ( P < 0.01 ) and positively correlated with Schirmer test results ( P < 0.01 ) . There was no significant correlation between symptom score and rose bengal staining , TBUT , or Schirmer test results ( P > 0.01 ) . Conclusions : Lower tear meniscus measurement with FD-OCT is an objective noninvasive test that correlates well with symptoms of dry eye disease and the Schirmer test Purpose : To determine the prevalence of dry eye syndrome , analyze the relationship between dry eye symptoms and signs , and identify associated risk factors for dry eye syndrome in an elderly Tibetan population at high altitude . Methods : A population -based survey was conducted from October 2006 to December 2006 . A stratified , clustered , r and om sampling procedure was used to select 2632 native Tibetan people ≥ 
    Output:
    
Associations between DED signs and symptoms are low and inconsistent , which may have implication s for monitoring the response to treatment , both in the clinic and in clinical trials .