CLINICAL SCIENCE
Concordance Between Patient and Clinician Assessment of Dry Eye Severity and Treatment Response in Taiwan Po-Ting Yeh, MD, MMS,* Hsu-Chih Chien, BS Pharm, MS,† Kwong Ng, MClinPharm, MPH,‡ Sung-Huei Tseng, MD,§ Wei-Li Chen, MD, PhD,* Yu-Chih Hou, MD,* I-Jong Wang, MD, PhD,* Hsiao-Sung Chu, MD MS,* Yea-Huei Kao Yang, BSPharm,† and Fung-Rong Hu, MD*
Purpose: Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response.
Methods: This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1–4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. Results: A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P , 0.001) and treatment response (rho = 0.22, P , 0.001).
Received for publication November 2, 2014; revision received January 23, 2015; accepted January 27, 2015. Published online ahead of print March 17, 2015. From the *Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; †Institute of Clinical Pharmacy and Pharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan; ‡Regional Market Access (Asia Pacific), Allergan Singapore Pte Ltd, Singapore, Singapore; and §Sung-Huei Tseng Ophthalmology Clinic, Tainan, Taiwan. Supported by Allergan Singapore Pte Ltd. Writing and editorial assistance were provided to the authors by Eddy Saputra, PhD, of In Vivo Communications (Asia) Pte Ltd and funded by Allergan Singapore Pte Ltd. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. K. Ng is an employee of Allergan Singapore Pte Ltd. H.-C. Chien and Y.-H. Kao Yang are consultants to Allergan Singapore Pte Ltd. The other authors have no conflicts of interest to disclose. Reprints: Fung-Rong Hu, MD, Department of Ophthalmology, National Taiwan University Hospital, Medical College, National Taiwan University, Taipei, Taiwan, No. 7, Chung Shan S Rd, Zhongzheng Dist, Taipei City 10002, Taiwan (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Conclusions: There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226. Key Words: concordance, disease severity, dry eye syndrome, keratoconjunctivitis sicca, patient-clinician assessment, treatment response (Cornea 2015;34:500–505)
D
ry eye disease (DED) is a multifactorial disease caused by inadequate tear production and/or rapid tear film evaporation as a result of inflammatory disease, environmental factors, hormonal changes, or aging.1 It has been shown to adversely impact quality of life, with health utilities for moderate-to-severe dry eyes reported to be similar to moderate-to-severe angina.2 The prevalence of DED varies worldwide and has been reported to be 2-fold higher in Asia than in the United States.3,4 Several risk factors have been identified for the development of DED, including increasing age, female gender, and menopausal status.5 The frequency and severity of DED have been observed to be higher in women compared with men in both the United States and Asia.6–9 The correlation between dry eye tests and symptoms of discomfort is generally weak because of the wide-ranging etiologies of DED and the great variability of clinical signs.10 As a consequence, no gold standard clinical test is widely accepted for diagnosing DED.11,12 In 2007, the subcommittee of the International Dry Eye Workshop (DEWS) recommended a standardized classification of disease severity that considered both signs and symptoms of DED.13,14 Although most studies have evaluated the correlation between clinical tests and symptoms, to date, only 1 study, conducted in 2005 (which predates the DEWS classifications), has evaluated the relationship between patient and clinician assessment of dry eye severity.15 The study demonstrated that clinicians often underestimated disease severity compared with patients’ self-assessment. As similar research is lacking in Asia, the objective of this study was to examine the concordance between patient and clinician assessment of DED severity and treatment response in Taiwan. Cornea Volume 34, Number 5, May 2015
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Cornea Volume 34, Number 5, May 2015
METHODS Study Subjects Participants in this cross-sectional study were recruited from the corneal clinic at the National Taiwan University Hospital (NTUH) in Taipei and a local ophthalmology clinic in Tainan, Taiwan, from August 2013 to November 2013. Patients enrolled in this study were .20 years of age with suspected DED defined by at least 1 positive Schirmer test (#10 mm per 5 minutes) in at least 1 eye within the past 12 months. Individuals who were pregnant or had cognitive or psychiatric deficits that precluded informed consent and the ability to complete the study questionnaire were excluded. Informed consent was obtained from the participants in accordance with the Declaration of Helsinki. The study protocol was approved by the institutional review boards at both sites, and it is registered on ClinicalTrials.gov (identifier: NCT01942226).
Patient Characteristics Participants were asked to complete a questionnaire designed to capture information including age, gender, menopausal status for female participants, employment status, duration of DED, and comorbidities.
Severity of DED Clinicians assessed DED severity based on the DEWS severity grading scheme, which considers both signs and symptoms of DED at every visit.13,14 Every patient underwent comprehensive ophthalmic examinations, and tests for dry eye included the slit-lamp examination, assessment of meibomian gland dysfunction (MGD), ocular surface fluorescence staining (Oxford scheme),16 tear film break-up time, and then the Schirmer test with anesthesia (only performed in the baseline visit).6 According to the DEWS severity scheme, dry eye severity was graded from level 1 to level 4, with higher levels indicating more severe DED. To differentiate between severity levels 1 and 2, corneal staining photographs were required. However, because staining photographs were not readily available for all participants, levels 1 and 2 could not be well differentiated. To avoid severe statistical error, only 3 groups of varying degree of severity were graded, namely, level 1 or 2, level 3, and level 4. Patient-reported DED severity was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Although the OSDI is not routinely used in clinical practice in Taiwan, it has been shown to be valid and reliable for quantifying the impact of dry eye on vision-related quality of life.17 The Chinese version of the OSDI questionnaire was supplied by Allergan, Irvine, CA. The validity and reliability of the Chinese OSDI have been independently tested and shown to be psychometrically robust.18 The OSDI questionnaire consists of 12 items designed to assess the symptoms of ocular irritation consistent with DED and their impact on vision-related functioning in the previous week. The OSDI consists of 3 subscales: ocular symptoms, vision-related function, and environmental triggers. It is scored on a scale Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Dry Eye Severity and Treatment Response
of 0 to 100, with higher scores representing greater disability. Based on the OSDI score, the ocular surface was defined as normal (0–12), mild (13–22), moderate (23–32), or severe (33–100).19 Clinicians were masked to patients’ OSDI scores.
Changes in Treatment Response At the study visit, clinicians used the English version of the Clinician Global Impression (CGI) rating scale to judge the overall change in dry eye signs and symptoms compared with patients’ baseline values. The results of the clinical assessment at the study visit were considered final and were used to be compared with patients’ baseline or first-time visit. The 7 response options of the CGI scale were marked worsening, moderate worsening, minimal worsening, unchanged, minimal improvement, moderate improvement, and marked improvement. Patients were also asked to recall their overall change of symptoms from baseline using the Subject Global Assessment (SGA) scale. The 5 response options of SGA were much worse, worse, about the same, improved, and much improved. For the purpose of this study, the SGA scale was translated into Chinese and validated linguistically by local experts (n = 10), achieving a content validity index of 1. The physicians were masked to the results of the SGA. Both the CGI and SGA scales were previously used as anchors to estimate the minimally clinically important difference for the overall OSDI score as described by Miller et al.19
Subgroup Analysis
Chalmers et al15 previously reported that .54% of the subjects aged above 65 years and 43% of the female subjects had their dry eye conditions underestimated by their clinicians. Therefore, subgroup analyses according to gender (male vs. female) and age ($65 vs. ,65 years) were conducted to evaluate whether similar findings were observed in this Asian population.
Statistical Analysis For descriptive statistics, the mean and SD were determined for continuous variables and frequency distributions for discrete variables. The concordance of dry eye severity grades and treatment response assessed by patients and clinicians were examined using the Spearman rank correlation coefficient (rho). A Fisher r-to-z transformation test was used to compare the correlation coefficients in the subgroup analyses for male versus female and age $65 versus ,65 years, respectively. For all analyses, 2-sided P values were reported and results were considered statistically significant if P , 0.05. All statistical analyses were performed using SAS software 9.3 (SAS Institute Inc 2013, Cary, NC).
RESULTS Between August and November 2013, 477 patients with dry eye symptoms were screened and met the inclusion criteria. Eleven patients were excluded because of either reluctance to participate in the study (n = 10, 2.1%) or www.corneajrnl.com |
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inability to complete the study questionnaire (n = 1, 0.2%). A total of 466 patients with DED were included in the study, in which 316 were from Taipei and 150 from Tainan. The mean age of the patients was 61.0 years with 74.0% being female. The 3 most common comorbidities were cataract, diabetes, and Sjögren syndrome (Table 1). Based on clinician assessment, 411 (88.3%) patients were graded as level 1 or 2 severity, 42 (9.0%) as level 3, and 13 (2.7%) as level 4. More than 80% of patients reported a Schirmer score of #5 mm per 5 minutes (Table 2). Based on patients’ self-assessment, 112 (24.0%) patients reported normal (0–12 points) symptoms, 97 (20.8%) reported mild symptoms (13–22 points), 80 (17.1%) reported moderate severity (23–32 points), and 177 (38.0%) severe DED (33– 100 points). In addition, 243 (52.1%) patients had their DED severity graded as milder by their clinician than by their selfreporting, whereas 18 (3.9%) patients had their DED severity graded as more severe by their clinician (Table 3). Because differentiation was not possible between levels 1 and 2 severity as assessed by clinicians, both levels were
combined when the level of concordance was examined that showed low agreement between clinician and patient assessments in terms of disease severity (rho = 0.166, P , 0.001). A sensitivity analysis was further conducted to examine the effect of potential overestimation of discordance by assuming a best-case scenario where patients who reported normal OSDI scores were assigned as level 1 severity and those reported mild symptoms assigned as level 2 severity. This analysis showed a correlation coefficient (rho) of 0.272, which was not significantly different from the initial result of 0.166 (P = 0.09) (Table 3). According to clinician CGI assessment, 48 (10.3%) patients were unchanged on their disease severity after treatment compared with baseline and 409 (88.0%) patients had minimal to marked improvement after treatment (Table 4). In contrast, 229 (49.2%) patients reported their dry eye symptoms being almost the same after treatment and 161 (34.6%) patients reported their symptoms improved or much improved. Overall, there was low agreement between patient and clinician assessment of treatment response after treatment
TABLE 1. Patient Characteristics
TABLE 2. Results of Dry Eye Clinical Tests Participants (N = 466)
Characteristics Men Women Age (all), mean 6 SD, yrs Age (women), mean 6 SD, yrs Age (male), mean 6 SD, yrs Employment status Employed Housewives Retired Unemployed Student DED duration ,3 mo 4–6 mo 7–12 mo .12 mo Menstrual status Normal menstrual cycle Premenopause Perimenopause Postmenopause Not reported Comorbidities Cataract Diabetes Sjögren syndrome Conjunctivitis Retinopathy Others*
n (%) 121 (26.0) 345 (74.0) 61.0 6 14.0 61.4 6 13.7 59.7 6 14.9 162 (34.8) 152 (32.6) 130 (27.9) 13 (2.8) 6 (1.3) 96 (20.6) 53 (11.4) 86 (18.5) 231 (49.6) 52 (15.1) 9 (2.6) 7 (2.0) 270 (78.3) 7 (2.0) 115 (24.7) 55 (11.8) 32 (6.9) 28 (6.0) 24 (5.2) 110 (23.6)
Participants (N = 466) Characteristics
Patients, n
Schirmer score (mm per 5 minutes) (OD) .5 mm 2–5 mm ,2 mm Schirmer score (mm per 5 minutes) (OS) .5 mm 2–5 mm ,2 mm Corneal signs With filamentary keratitis (OD) With filamentary keratitis (OS) Ocular surface fluorescein staining Oxford scheme (OD)† Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Missing Oxford scheme (OS)† Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Missing
4.1 (2.2)* 81 313 72 4.1 (2.3)* 86 302 78
%
18.5 64.8 16.7
27 27
5.8 5.8
168 202 60 26 8 1 1
36.1 43.4 12.9 5.6 1.7 0.2 0.2
177 198 54 23 11 2 1
38.1 42.5 11.6 4.9 2.4 0.4 0.2
17.4 67.2 15.5
*Other comorbidities (.1%) included glaucoma (3.9%), keratitis (4.3%), keratoplasty (1.5%), refractive surgery (1.7%), systemic lupus erythematosus (1.1%), rheumatoid arthritis (3.7%), and thyroidism (4.1%).
Results of tear break-up time were not analyzed. *Mean (SD). †Oxford scheme is a grading scale for the assessment of corneal and conjunctival fluorescein staining.16
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Dry Eye Severity and Treatment Response
DISCUSSION
TABLE 3. Concordance Between Patient and Clinician Assessment of Disease Severity Clinician Overall Assessment, n (%) Subgroup All participants (N = 466)
Male (n = 121)
Female (n = 345)
$65 yrs (n = 204)
,65 yrs (n = 262)
Patient Assessment (OSDI)
Level 1 or Level 2 Level 3 4
Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100)
194 (41.7) 13 (2.8) 2 (0.4) 74 (15.9) 3 (0.6) 3 (0.6) 143 (30.7) 26 (5.6) 8 (1.7) 60 (49.6) 4 (3.3) 0 25 (20.7) 26 (21.5) 134 (38.8)
1 (0.8) 0 3 (2.5) 2 (1.6) 9 (2.6) 2 (0.6)
49 (14.2) 2 (0.6) 3 (0.9) 117 (33.9) 23 (6.7) 6 (1.7) 95 (46.5) 4 (2.0) 2 (1.0) 33 (16.1) 2 (1.0) 2 (1.0) 51 (25.0) 11 (5.4) 4 (2.0) 99 (37.8) 9 (3.4) 0 41 (15.7) 1 (0.4) 1 (0.4) 92 (35.1) 15 (5.7) 4 (1.5)
(rho = 0.22, P , 0.001), with a tendency for clinicians to report greater treatment response compared with the patientreported SGA response. We also conducted subgroup analyses by gender (male vs. female) and age ($65 vs. ,65 years). As shown in Table 3, agreement between patient and clinician assessment in dry eye severity was low in both male (rho = 0.13, P = 0.17) and female (rho = 0.17, P = 0.002) patients, which were not statistically different (P = 0.70). Similarly, subgroup analysis by age group showed weak agreement between patient and clinician assessment of dry eye severity. The correlation coefficients were 0.22 (P = 0.002) for the $65-year-old group and 0.130 (P = 0.035) for the ,65-year-old group, which were not statistically different (P = 0.33).
This study shows poor correlation between clinician and patient assessments in terms of disease severity and response to DED treatment. Patient-assessed DED was generally reported to be more severe compared with clinician-assessed DED. Nearly half of patients had their DED severity graded milder by their clinicians, indicating that clinicians may underestimate DED severity in this population. According to clinician assessment, the majority of the patients improved after treatment, whereas only one-third of patients reported improvement after treatment. The impact of underrecognizing DED severity is compounded by the overestimation of treatment response, representing dual obstacles to achieving optimal care for patients with DED in clinical practice. Compared with the study by Chalmers et al,15 where moderate-to-high correlation was observed, the degree of disparities between patient and clinician assessment in disease severity was greater in this study. It was noteworthy that different methods and classification in assessing DED severity were used. In our study, the OSDI and DEWS severity grading scheme were used by patients and clinicians to determine disease severity, respectively. In contrast, the study by Chalmers et al15 was conducted before the consensus statement on classification of dry eye severity was published by DEWS.13 Chalmers et al15 used different quality of life questionnaires (eg, Impact of Dry Eye on Everyday Life) and a global clinician grading based on a combination of routine clinical tests and patients’ symptoms to determine disease severity. The use of quality of life questionnaires as part of the clinician assessment in the study by Chalmers et al15 could explain the higher correlation compared with that observed in this study. In addition, cultural differences may exist in doctor–patient communication between Asian and Western countries. Evidence suggests that doctor–patient communication tends to be more unidirectional in the Southeast Asian setting with limited input from the patient compared with the partnership communication style in Western culture.20 Effective doctor–patient communication is particularly important in DED given the subjective nature of this symptomatic disease. Although this study did not differentiate between level 1 and 2 severity, the proportion of dry eye severity in this
TABLE 4. Concordance of Subject Global Assessment and Clinician Global Impression Rating Scales CGI (N = 465*)
SGA Much worse Worse About the same Improved Much improved
Marked Worsening
Moderate Worsening
Minimal Worsening
Unchanged
Minimal Improvement
Moderate Improvement
Marked Improvement
0 1 0
0 0 1
0 1 2
0 10 32
2 31 100
0 28 86
0 2 8
0 0
0 0
3 0
5 1
49 2
83 2
10 6
*Missing data from 1 patient (which was excluded for calculating percentages).
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study was similar to that published by Song et al.21 In South Korea, where dry eye severity was based on a classification modified from the DEWS guideline, the prevalence of patients with dry eye at level 1 was 47.5%, 33.5% at 2 (ie, 81.0% if levels 1 and 2 were combined), 9.1% at level 3, and 1.1% at level 4. These numbers closely related to our findings of 88.2% at level 1 or 2, 9.0% at level 3, and 2.6% at level 4. It is likely that clinicians in this study gave preferential weight to clinical signs over symptoms in the event of a discrepancy between clinical signs and a patient’s symptoms. As a result, the proportion of patients assessed by clinicians as having level 3 or 4 severity (11.7%) is much lower compared with that assessed by patients having severe disease (38.0%). The low agreement between patient and clinician assessment observed in this study may be further explained by the current categorical DEWS classification of DED severity. Sullivan et al22 evaluated distributions of clinical signs and symptoms against a continuous composite severity index. Recent research has shown the validity of tear osmolarity as one of the best objective measures of dry eye.23–25 The observed variability in tear osmolarity between eyes or multiple measurements in the same eye has established a means of identifying patients with mild tear dysfunction, given that such variability is not observed in normal tears. Hence, measuring tear osmolarity may be useful in diagnosing and grading DED severity. This study has several strengths. It is believed that this is the first Asian study to examine concordance of dry eye severity and treatment response assessed by patients and clinicians. The study also has a relatively large sample size in comparison with other studies.15,26 In addition, this study used the validated OSDI questionnaire, which has been shown to be a reliable disease-specific questionnaire to capture the patient’s perspective on the impact of DED severity on vision-related quality of life. In comparison, most previous studies11,26,27 did not include any validated quality of life instruments in assessing the association between signs and symptoms in dry eye. This study also has limitations. Our study focused on a group of symptomatic DED patients whose Schirmer test results were ,10 mm, which was likely to be more “severe” or aqueous tear deficient in nature. In this study, no distinction was made between aqueous tear deficient dry eye versus other types of DED that were evaporative, for example, MGD, given that the assessment of MGD in this study was only performed under slit-lamp examination and the level of severity was not quantified. Furthermore, a subset of patients with MGD who were symptomatic but with a Schirmer test results of .10 mm would have been excluded in this study. Recently, a special type of DED with corneal sensory receptor dysfunction induced central cornea–projected pain had been widely discussed.28–30 This subtype of DED might be asymptomatic on the questionnaires because of desensitized ocular surfaces. Our study was unable to identify these patients into a further subset. Therefore, the overall conclusion of this study might not applicable to these DED patients. The study was unable to differentiate between severity levels 1 and 2 assessed by the
clinicians. Subsequently, this study may have overestimated the discordance between patient and clinician assessment of DED severity. However, a sensitivity analysis was conducted and showed that the level of agreement remained low even when a best-case scenario was assumed for perfect concordance for level 1 and 2 severity. Both the CGI and SGA scales require clinicians and patients to compare their assessments with baseline or first-time visit. Patients were also required to recall the use of any dry eye treatment over the past 1 month to 1 year. Consequently, there may be a recall bias on patients’ reported medication use and treatment response. The results presented in this report were based on a cross-sectional study; therefore, it does not capture the correlation and treatment response over time. Patients may also adapt to dry eye symptoms over time, which may have an impact on the concordance between patient and clinician assessment in disease severity and treatment response longitudinally. The results from this study may have several clinical implications. For instance, clinicians may need to consider systematically taking into account patient perspectives of DED management and assessment by including a validated questionnaire (eg, OSDI) to assess DED symptoms in routine practice to aid doctor–patient communication and determine optimal treatment strategy. Compared with other questionnaires, the OSDI is a more convenient option for clinical use because of its shorter completion time.31 The low agreement between patient and clinician assessment may indicate that ophthalmologists in Taiwan need better and more accurate quantitative tools to improve the concordance in severity assessment. To date, there is no available universally accepted gold standard test that is reliable to assess dry eye severity. Although recent research has shown the validity of tear osmolarity as one of the best objective measures of dry eye, such technology is not yet widely available in Asia. Many newer techniques such as inferior tear meniscus height measured by optical coherence tomography, tear film composition analysis, and measurement of tear inflammatory biomarkers have been developed to evaluate and measure tear film conditions in vivo. It is hoped that these new methods would be integrated into clinical practice for diagnosis, classification, and severity grading of DEDs in the near future.24,32,33 Furthermore, symptoms alone are not enough to diagnose and manage DED. A consensus of clinical signs that better captures the totality of DED is needed.25 However, clinicians tend to use the most convenient tests for DED diagnosis. In a survey of clinicians’ attitudes towards diagnostic tests and therapies for DED, Turner et al34 reported that clinicians valued “ease of use” or “time taken to perform the tests” over the “evidence” of DED in their patients. In summary, there are marked differences in dry eye severity and treatment response as assessed by patients and clinicians. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears. The findings of this study may highlight the need for further redefining DED severity, as well as the routine use of a validated disease-specific questionnaire in clinical practice in Taiwan to ensure better treatment choices.
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ACKNOWLEDGMENTS The authors thank Emily Cheng (Allergan Taiwan Pte Ltd) for her administrative support throughout the conduct and execution of this study. REFERENCES 1. Kastelan S, Tomic M, Salopek-Rabatic J, et al. Diagnostic procedures and management of dry eye. Biomed Res Int. 2013;2013:309723. 2. Schiffman RM, Walt JG, Jacobsen G, et al. Utility assessment among patients with dry eye disease. Ophthalmology. 2003;110:1412–1419. 3. Jie Y, Xu L, Wu YY, et al. Prevalence of dry eye among adult Chinese in the Beijing Eye Study. Eye (Lond). 2009;23:688–693. 4. Lekhanont K, Rojanaporn D, Chuck RS, et al. Prevalence of dry eye in Bangkok, Thailand. Cornea. 2006;25:1162–1167. 5. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009;3:405–412. 6. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology. 2003;110:1096–1101. 7. Schaumberg DA, Sullivan DA, Buring JE, et al. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136:318–326. 8. Schaumberg DA, Uchino M, Christen WG, et al. Patient reported differences in dry eye disease between men and women: impact, management, and patient satisfaction. PLoS One 2013;8:e76121. 9. Uchino M, Nishiwaki Y, Michikawa T, et al. Prevalence and risk factors of dry eye disease in Japan: Koumi study. Ophthalmology. 2011;118: 2361–2367. 10. Pflugfelder SC, Solomon A, Stern ME. The diagnosis and management of dry eye: a twenty-five-year review. Cornea. 2000;19:644–649. 11. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea. 2004;23: 762–770. 12. Johnson ME. The association between symptoms of discomfort and signs in dry eye. Ocul Surf. 2009;7:199–211. 13. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5:93–107. 14. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25: 900–907. 15. Chalmers RL, Begley CG, Edrington T, et al. The agreement between self-assessment and clinician assessment of dry eye severity. Cornea. 2005;24:804–810. 16. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003;22:640–650.
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17. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118:615–621. 18. Li M, Gong L, Chapin WJ, et al. Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci. 2012;53:5722–5727. 19. Miller KL, Walt JG, Mink DR, et al. Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmol. 2010; 128:94–101. 20. Claramita M, Nugraheni MD, van Dalen J, et al. Doctor-patient communication in Southeast Asia: a different culture? Adv Health Sci Educ Theory Pract. 2013;18:15–31. 21. Song JS, Hyon JY, Lee D, et al. Current practice pattern for dry eye patients in South Korea: a multicenter study. Korean J Ophthalmol. 2014;28:115–121. 22. Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51:6125–6130. 23. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011;151:792– 798.e1. 24. Foulks GN, Pflugfelder SC. New testing options for diagnosing and grading dry eye disease. Am J Ophthalmol. 2014;157:1122–1129. 25. Sullivan BD, Crews LA, Messmer EM, et al. Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications. Acta Ophthalmol. 2014;92:161–166. 26. Begley CG, Chalmers RL, Abetz L, et al. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci. 2003;44: 4753–4761. 27. Lin PY, Cheng CY, Hsu WM, et al. Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Invest Ophthalmol Vis Sci. 2005;46:1593–1598. 28. Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain: is it real? Ocul Surf. 2009;7:28–40. 29. Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf. 2012;10:2–14. 30. Chao C, Golebiowski B, Stapleton F. The role of corneal innervation in LASIK-induced neuropathic dry eye. Ocul Surf. 2014;12:32–45. 31. Grubbs JR Jr, Tolleson-Rinehart S, Huynh K, et al. A review of quality of life measures in dry eye questionnaires. Cornea. 2014;33:215–218. 32. Sullivan B. Challenges in using signs and symptoms to evaluate new biomarkers of dry eye disease. Ocul Surf. 2014;12:2–9. 33. Bron AJ, Tomlinson A, Foulks GN, et al. Rethinking dry eye disease: a perspective on clinical implications. Ocul Surf. 2014;12:S1–S31. 34. Turner AW, Layton CJ, Bron AJ. Survey of eye practitioners’ attitudes towards diagnostic tests and therapies for dry eye disease. Clin Experiment Ophthalmol. 2005;33:351–355.
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Concordance Between Patient and Clinician Assessment of Dry Eye Severity and Treatment Response in Taiwan Po-Ting Yeh, MD, MMS,* Hsu-Chih Chien, BS Pharm, MS,† Kwong Ng, MClinPharm, MPH,‡ Sung-Huei Tseng, MD,§ Wei-Li Chen, MD, PhD,* Yu-Chih Hou, MD,* I-Jong Wang, MD, PhD,* Hsiao-Sung Chu, MD MS,* Yea-Huei Kao Yang, BSPharm,† and Fung-Rong Hu, MD*
Purpose: Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response.
Methods: This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1–4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. Results: A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P , 0.001) and treatment response (rho = 0.22, P , 0.001).
Received for publication November 2, 2014; revision received January 23, 2015; accepted January 27, 2015. Published online ahead of print March 17, 2015. From the *Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; †Institute of Clinical Pharmacy and Pharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan; ‡Regional Market Access (Asia Pacific), Allergan Singapore Pte Ltd, Singapore, Singapore; and §Sung-Huei Tseng Ophthalmology Clinic, Tainan, Taiwan. Supported by Allergan Singapore Pte Ltd. Writing and editorial assistance were provided to the authors by Eddy Saputra, PhD, of In Vivo Communications (Asia) Pte Ltd and funded by Allergan Singapore Pte Ltd. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. K. Ng is an employee of Allergan Singapore Pte Ltd. H.-C. Chien and Y.-H. Kao Yang are consultants to Allergan Singapore Pte Ltd. The other authors have no conflicts of interest to disclose. Reprints: Fung-Rong Hu, MD, Department of Ophthalmology, National Taiwan University Hospital, Medical College, National Taiwan University, Taipei, Taiwan, No. 7, Chung Shan S Rd, Zhongzheng Dist, Taipei City 10002, Taiwan (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Conclusions: There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226. Key Words: concordance, disease severity, dry eye syndrome, keratoconjunctivitis sicca, patient-clinician assessment, treatment response (Cornea 2015;34:500–505)
D
ry eye disease (DED) is a multifactorial disease caused by inadequate tear production and/or rapid tear film evaporation as a result of inflammatory disease, environmental factors, hormonal changes, or aging.1 It has been shown to adversely impact quality of life, with health utilities for moderate-to-severe dry eyes reported to be similar to moderate-to-severe angina.2 The prevalence of DED varies worldwide and has been reported to be 2-fold higher in Asia than in the United States.3,4 Several risk factors have been identified for the development of DED, including increasing age, female gender, and menopausal status.5 The frequency and severity of DED have been observed to be higher in women compared with men in both the United States and Asia.6–9 The correlation between dry eye tests and symptoms of discomfort is generally weak because of the wide-ranging etiologies of DED and the great variability of clinical signs.10 As a consequence, no gold standard clinical test is widely accepted for diagnosing DED.11,12 In 2007, the subcommittee of the International Dry Eye Workshop (DEWS) recommended a standardized classification of disease severity that considered both signs and symptoms of DED.13,14 Although most studies have evaluated the correlation between clinical tests and symptoms, to date, only 1 study, conducted in 2005 (which predates the DEWS classifications), has evaluated the relationship between patient and clinician assessment of dry eye severity.15 The study demonstrated that clinicians often underestimated disease severity compared with patients’ self-assessment. As similar research is lacking in Asia, the objective of this study was to examine the concordance between patient and clinician assessment of DED severity and treatment response in Taiwan. Cornea Volume 34, Number 5, May 2015
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Cornea Volume 34, Number 5, May 2015
METHODS Study Subjects Participants in this cross-sectional study were recruited from the corneal clinic at the National Taiwan University Hospital (NTUH) in Taipei and a local ophthalmology clinic in Tainan, Taiwan, from August 2013 to November 2013. Patients enrolled in this study were .20 years of age with suspected DED defined by at least 1 positive Schirmer test (#10 mm per 5 minutes) in at least 1 eye within the past 12 months. Individuals who were pregnant or had cognitive or psychiatric deficits that precluded informed consent and the ability to complete the study questionnaire were excluded. Informed consent was obtained from the participants in accordance with the Declaration of Helsinki. The study protocol was approved by the institutional review boards at both sites, and it is registered on ClinicalTrials.gov (identifier: NCT01942226).
Patient Characteristics Participants were asked to complete a questionnaire designed to capture information including age, gender, menopausal status for female participants, employment status, duration of DED, and comorbidities.
Severity of DED Clinicians assessed DED severity based on the DEWS severity grading scheme, which considers both signs and symptoms of DED at every visit.13,14 Every patient underwent comprehensive ophthalmic examinations, and tests for dry eye included the slit-lamp examination, assessment of meibomian gland dysfunction (MGD), ocular surface fluorescence staining (Oxford scheme),16 tear film break-up time, and then the Schirmer test with anesthesia (only performed in the baseline visit).6 According to the DEWS severity scheme, dry eye severity was graded from level 1 to level 4, with higher levels indicating more severe DED. To differentiate between severity levels 1 and 2, corneal staining photographs were required. However, because staining photographs were not readily available for all participants, levels 1 and 2 could not be well differentiated. To avoid severe statistical error, only 3 groups of varying degree of severity were graded, namely, level 1 or 2, level 3, and level 4. Patient-reported DED severity was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Although the OSDI is not routinely used in clinical practice in Taiwan, it has been shown to be valid and reliable for quantifying the impact of dry eye on vision-related quality of life.17 The Chinese version of the OSDI questionnaire was supplied by Allergan, Irvine, CA. The validity and reliability of the Chinese OSDI have been independently tested and shown to be psychometrically robust.18 The OSDI questionnaire consists of 12 items designed to assess the symptoms of ocular irritation consistent with DED and their impact on vision-related functioning in the previous week. The OSDI consists of 3 subscales: ocular symptoms, vision-related function, and environmental triggers. It is scored on a scale Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Dry Eye Severity and Treatment Response
of 0 to 100, with higher scores representing greater disability. Based on the OSDI score, the ocular surface was defined as normal (0–12), mild (13–22), moderate (23–32), or severe (33–100).19 Clinicians were masked to patients’ OSDI scores.
Changes in Treatment Response At the study visit, clinicians used the English version of the Clinician Global Impression (CGI) rating scale to judge the overall change in dry eye signs and symptoms compared with patients’ baseline values. The results of the clinical assessment at the study visit were considered final and were used to be compared with patients’ baseline or first-time visit. The 7 response options of the CGI scale were marked worsening, moderate worsening, minimal worsening, unchanged, minimal improvement, moderate improvement, and marked improvement. Patients were also asked to recall their overall change of symptoms from baseline using the Subject Global Assessment (SGA) scale. The 5 response options of SGA were much worse, worse, about the same, improved, and much improved. For the purpose of this study, the SGA scale was translated into Chinese and validated linguistically by local experts (n = 10), achieving a content validity index of 1. The physicians were masked to the results of the SGA. Both the CGI and SGA scales were previously used as anchors to estimate the minimally clinically important difference for the overall OSDI score as described by Miller et al.19
Subgroup Analysis
Chalmers et al15 previously reported that .54% of the subjects aged above 65 years and 43% of the female subjects had their dry eye conditions underestimated by their clinicians. Therefore, subgroup analyses according to gender (male vs. female) and age ($65 vs. ,65 years) were conducted to evaluate whether similar findings were observed in this Asian population.
Statistical Analysis For descriptive statistics, the mean and SD were determined for continuous variables and frequency distributions for discrete variables. The concordance of dry eye severity grades and treatment response assessed by patients and clinicians were examined using the Spearman rank correlation coefficient (rho). A Fisher r-to-z transformation test was used to compare the correlation coefficients in the subgroup analyses for male versus female and age $65 versus ,65 years, respectively. For all analyses, 2-sided P values were reported and results were considered statistically significant if P , 0.05. All statistical analyses were performed using SAS software 9.3 (SAS Institute Inc 2013, Cary, NC).
RESULTS Between August and November 2013, 477 patients with dry eye symptoms were screened and met the inclusion criteria. Eleven patients were excluded because of either reluctance to participate in the study (n = 10, 2.1%) or www.corneajrnl.com |
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inability to complete the study questionnaire (n = 1, 0.2%). A total of 466 patients with DED were included in the study, in which 316 were from Taipei and 150 from Tainan. The mean age of the patients was 61.0 years with 74.0% being female. The 3 most common comorbidities were cataract, diabetes, and Sjögren syndrome (Table 1). Based on clinician assessment, 411 (88.3%) patients were graded as level 1 or 2 severity, 42 (9.0%) as level 3, and 13 (2.7%) as level 4. More than 80% of patients reported a Schirmer score of #5 mm per 5 minutes (Table 2). Based on patients’ self-assessment, 112 (24.0%) patients reported normal (0–12 points) symptoms, 97 (20.8%) reported mild symptoms (13–22 points), 80 (17.1%) reported moderate severity (23–32 points), and 177 (38.0%) severe DED (33– 100 points). In addition, 243 (52.1%) patients had their DED severity graded as milder by their clinician than by their selfreporting, whereas 18 (3.9%) patients had their DED severity graded as more severe by their clinician (Table 3). Because differentiation was not possible between levels 1 and 2 severity as assessed by clinicians, both levels were
combined when the level of concordance was examined that showed low agreement between clinician and patient assessments in terms of disease severity (rho = 0.166, P , 0.001). A sensitivity analysis was further conducted to examine the effect of potential overestimation of discordance by assuming a best-case scenario where patients who reported normal OSDI scores were assigned as level 1 severity and those reported mild symptoms assigned as level 2 severity. This analysis showed a correlation coefficient (rho) of 0.272, which was not significantly different from the initial result of 0.166 (P = 0.09) (Table 3). According to clinician CGI assessment, 48 (10.3%) patients were unchanged on their disease severity after treatment compared with baseline and 409 (88.0%) patients had minimal to marked improvement after treatment (Table 4). In contrast, 229 (49.2%) patients reported their dry eye symptoms being almost the same after treatment and 161 (34.6%) patients reported their symptoms improved or much improved. Overall, there was low agreement between patient and clinician assessment of treatment response after treatment
TABLE 1. Patient Characteristics
TABLE 2. Results of Dry Eye Clinical Tests Participants (N = 466)
Characteristics Men Women Age (all), mean 6 SD, yrs Age (women), mean 6 SD, yrs Age (male), mean 6 SD, yrs Employment status Employed Housewives Retired Unemployed Student DED duration ,3 mo 4–6 mo 7–12 mo .12 mo Menstrual status Normal menstrual cycle Premenopause Perimenopause Postmenopause Not reported Comorbidities Cataract Diabetes Sjögren syndrome Conjunctivitis Retinopathy Others*
n (%) 121 (26.0) 345 (74.0) 61.0 6 14.0 61.4 6 13.7 59.7 6 14.9 162 (34.8) 152 (32.6) 130 (27.9) 13 (2.8) 6 (1.3) 96 (20.6) 53 (11.4) 86 (18.5) 231 (49.6) 52 (15.1) 9 (2.6) 7 (2.0) 270 (78.3) 7 (2.0) 115 (24.7) 55 (11.8) 32 (6.9) 28 (6.0) 24 (5.2) 110 (23.6)
Participants (N = 466) Characteristics
Patients, n
Schirmer score (mm per 5 minutes) (OD) .5 mm 2–5 mm ,2 mm Schirmer score (mm per 5 minutes) (OS) .5 mm 2–5 mm ,2 mm Corneal signs With filamentary keratitis (OD) With filamentary keratitis (OS) Ocular surface fluorescein staining Oxford scheme (OD)† Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Missing Oxford scheme (OS)† Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Missing
4.1 (2.2)* 81 313 72 4.1 (2.3)* 86 302 78
%
18.5 64.8 16.7
27 27
5.8 5.8
168 202 60 26 8 1 1
36.1 43.4 12.9 5.6 1.7 0.2 0.2
177 198 54 23 11 2 1
38.1 42.5 11.6 4.9 2.4 0.4 0.2
17.4 67.2 15.5
*Other comorbidities (.1%) included glaucoma (3.9%), keratitis (4.3%), keratoplasty (1.5%), refractive surgery (1.7%), systemic lupus erythematosus (1.1%), rheumatoid arthritis (3.7%), and thyroidism (4.1%).
Results of tear break-up time were not analyzed. *Mean (SD). †Oxford scheme is a grading scale for the assessment of corneal and conjunctival fluorescein staining.16
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Dry Eye Severity and Treatment Response
DISCUSSION
TABLE 3. Concordance Between Patient and Clinician Assessment of Disease Severity Clinician Overall Assessment, n (%) Subgroup All participants (N = 466)
Male (n = 121)
Female (n = 345)
$65 yrs (n = 204)
,65 yrs (n = 262)
Patient Assessment (OSDI)
Level 1 or Level 2 Level 3 4
Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100) Normal (0–12) or mild (13–22) Moderate (23–32) Severe (33–100)
194 (41.7) 13 (2.8) 2 (0.4) 74 (15.9) 3 (0.6) 3 (0.6) 143 (30.7) 26 (5.6) 8 (1.7) 60 (49.6) 4 (3.3) 0 25 (20.7) 26 (21.5) 134 (38.8)
1 (0.8) 0 3 (2.5) 2 (1.6) 9 (2.6) 2 (0.6)
49 (14.2) 2 (0.6) 3 (0.9) 117 (33.9) 23 (6.7) 6 (1.7) 95 (46.5) 4 (2.0) 2 (1.0) 33 (16.1) 2 (1.0) 2 (1.0) 51 (25.0) 11 (5.4) 4 (2.0) 99 (37.8) 9 (3.4) 0 41 (15.7) 1 (0.4) 1 (0.4) 92 (35.1) 15 (5.7) 4 (1.5)
(rho = 0.22, P , 0.001), with a tendency for clinicians to report greater treatment response compared with the patientreported SGA response. We also conducted subgroup analyses by gender (male vs. female) and age ($65 vs. ,65 years). As shown in Table 3, agreement between patient and clinician assessment in dry eye severity was low in both male (rho = 0.13, P = 0.17) and female (rho = 0.17, P = 0.002) patients, which were not statistically different (P = 0.70). Similarly, subgroup analysis by age group showed weak agreement between patient and clinician assessment of dry eye severity. The correlation coefficients were 0.22 (P = 0.002) for the $65-year-old group and 0.130 (P = 0.035) for the ,65-year-old group, which were not statistically different (P = 0.33).
This study shows poor correlation between clinician and patient assessments in terms of disease severity and response to DED treatment. Patient-assessed DED was generally reported to be more severe compared with clinician-assessed DED. Nearly half of patients had their DED severity graded milder by their clinicians, indicating that clinicians may underestimate DED severity in this population. According to clinician assessment, the majority of the patients improved after treatment, whereas only one-third of patients reported improvement after treatment. The impact of underrecognizing DED severity is compounded by the overestimation of treatment response, representing dual obstacles to achieving optimal care for patients with DED in clinical practice. Compared with the study by Chalmers et al,15 where moderate-to-high correlation was observed, the degree of disparities between patient and clinician assessment in disease severity was greater in this study. It was noteworthy that different methods and classification in assessing DED severity were used. In our study, the OSDI and DEWS severity grading scheme were used by patients and clinicians to determine disease severity, respectively. In contrast, the study by Chalmers et al15 was conducted before the consensus statement on classification of dry eye severity was published by DEWS.13 Chalmers et al15 used different quality of life questionnaires (eg, Impact of Dry Eye on Everyday Life) and a global clinician grading based on a combination of routine clinical tests and patients’ symptoms to determine disease severity. The use of quality of life questionnaires as part of the clinician assessment in the study by Chalmers et al15 could explain the higher correlation compared with that observed in this study. In addition, cultural differences may exist in doctor–patient communication between Asian and Western countries. Evidence suggests that doctor–patient communication tends to be more unidirectional in the Southeast Asian setting with limited input from the patient compared with the partnership communication style in Western culture.20 Effective doctor–patient communication is particularly important in DED given the subjective nature of this symptomatic disease. Although this study did not differentiate between level 1 and 2 severity, the proportion of dry eye severity in this
TABLE 4. Concordance of Subject Global Assessment and Clinician Global Impression Rating Scales CGI (N = 465*)
SGA Much worse Worse About the same Improved Much improved
Marked Worsening
Moderate Worsening
Minimal Worsening
Unchanged
Minimal Improvement
Moderate Improvement
Marked Improvement
0 1 0
0 0 1
0 1 2
0 10 32
2 31 100
0 28 86
0 2 8
0 0
0 0
3 0
5 1
49 2
83 2
10 6
*Missing data from 1 patient (which was excluded for calculating percentages).
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study was similar to that published by Song et al.21 In South Korea, where dry eye severity was based on a classification modified from the DEWS guideline, the prevalence of patients with dry eye at level 1 was 47.5%, 33.5% at 2 (ie, 81.0% if levels 1 and 2 were combined), 9.1% at level 3, and 1.1% at level 4. These numbers closely related to our findings of 88.2% at level 1 or 2, 9.0% at level 3, and 2.6% at level 4. It is likely that clinicians in this study gave preferential weight to clinical signs over symptoms in the event of a discrepancy between clinical signs and a patient’s symptoms. As a result, the proportion of patients assessed by clinicians as having level 3 or 4 severity (11.7%) is much lower compared with that assessed by patients having severe disease (38.0%). The low agreement between patient and clinician assessment observed in this study may be further explained by the current categorical DEWS classification of DED severity. Sullivan et al22 evaluated distributions of clinical signs and symptoms against a continuous composite severity index. Recent research has shown the validity of tear osmolarity as one of the best objective measures of dry eye.23–25 The observed variability in tear osmolarity between eyes or multiple measurements in the same eye has established a means of identifying patients with mild tear dysfunction, given that such variability is not observed in normal tears. Hence, measuring tear osmolarity may be useful in diagnosing and grading DED severity. This study has several strengths. It is believed that this is the first Asian study to examine concordance of dry eye severity and treatment response assessed by patients and clinicians. The study also has a relatively large sample size in comparison with other studies.15,26 In addition, this study used the validated OSDI questionnaire, which has been shown to be a reliable disease-specific questionnaire to capture the patient’s perspective on the impact of DED severity on vision-related quality of life. In comparison, most previous studies11,26,27 did not include any validated quality of life instruments in assessing the association between signs and symptoms in dry eye. This study also has limitations. Our study focused on a group of symptomatic DED patients whose Schirmer test results were ,10 mm, which was likely to be more “severe” or aqueous tear deficient in nature. In this study, no distinction was made between aqueous tear deficient dry eye versus other types of DED that were evaporative, for example, MGD, given that the assessment of MGD in this study was only performed under slit-lamp examination and the level of severity was not quantified. Furthermore, a subset of patients with MGD who were symptomatic but with a Schirmer test results of .10 mm would have been excluded in this study. Recently, a special type of DED with corneal sensory receptor dysfunction induced central cornea–projected pain had been widely discussed.28–30 This subtype of DED might be asymptomatic on the questionnaires because of desensitized ocular surfaces. Our study was unable to identify these patients into a further subset. Therefore, the overall conclusion of this study might not applicable to these DED patients. The study was unable to differentiate between severity levels 1 and 2 assessed by the
clinicians. Subsequently, this study may have overestimated the discordance between patient and clinician assessment of DED severity. However, a sensitivity analysis was conducted and showed that the level of agreement remained low even when a best-case scenario was assumed for perfect concordance for level 1 and 2 severity. Both the CGI and SGA scales require clinicians and patients to compare their assessments with baseline or first-time visit. Patients were also required to recall the use of any dry eye treatment over the past 1 month to 1 year. Consequently, there may be a recall bias on patients’ reported medication use and treatment response. The results presented in this report were based on a cross-sectional study; therefore, it does not capture the correlation and treatment response over time. Patients may also adapt to dry eye symptoms over time, which may have an impact on the concordance between patient and clinician assessment in disease severity and treatment response longitudinally. The results from this study may have several clinical implications. For instance, clinicians may need to consider systematically taking into account patient perspectives of DED management and assessment by including a validated questionnaire (eg, OSDI) to assess DED symptoms in routine practice to aid doctor–patient communication and determine optimal treatment strategy. Compared with other questionnaires, the OSDI is a more convenient option for clinical use because of its shorter completion time.31 The low agreement between patient and clinician assessment may indicate that ophthalmologists in Taiwan need better and more accurate quantitative tools to improve the concordance in severity assessment. To date, there is no available universally accepted gold standard test that is reliable to assess dry eye severity. Although recent research has shown the validity of tear osmolarity as one of the best objective measures of dry eye, such technology is not yet widely available in Asia. Many newer techniques such as inferior tear meniscus height measured by optical coherence tomography, tear film composition analysis, and measurement of tear inflammatory biomarkers have been developed to evaluate and measure tear film conditions in vivo. It is hoped that these new methods would be integrated into clinical practice for diagnosis, classification, and severity grading of DEDs in the near future.24,32,33 Furthermore, symptoms alone are not enough to diagnose and manage DED. A consensus of clinical signs that better captures the totality of DED is needed.25 However, clinicians tend to use the most convenient tests for DED diagnosis. In a survey of clinicians’ attitudes towards diagnostic tests and therapies for DED, Turner et al34 reported that clinicians valued “ease of use” or “time taken to perform the tests” over the “evidence” of DED in their patients. In summary, there are marked differences in dry eye severity and treatment response as assessed by patients and clinicians. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears. The findings of this study may highlight the need for further redefining DED severity, as well as the routine use of a validated disease-specific questionnaire in clinical practice in Taiwan to ensure better treatment choices.
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ACKNOWLEDGMENTS The authors thank Emily Cheng (Allergan Taiwan Pte Ltd) for her administrative support throughout the conduct and execution of this study. REFERENCES 1. Kastelan S, Tomic M, Salopek-Rabatic J, et al. Diagnostic procedures and management of dry eye. Biomed Res Int. 2013;2013:309723. 2. Schiffman RM, Walt JG, Jacobsen G, et al. Utility assessment among patients with dry eye disease. Ophthalmology. 2003;110:1412–1419. 3. Jie Y, Xu L, Wu YY, et al. Prevalence of dry eye among adult Chinese in the Beijing Eye Study. Eye (Lond). 2009;23:688–693. 4. Lekhanont K, Rojanaporn D, Chuck RS, et al. Prevalence of dry eye in Bangkok, Thailand. Cornea. 2006;25:1162–1167. 5. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009;3:405–412. 6. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology. 2003;110:1096–1101. 7. Schaumberg DA, Sullivan DA, Buring JE, et al. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136:318–326. 8. Schaumberg DA, Uchino M, Christen WG, et al. Patient reported differences in dry eye disease between men and women: impact, management, and patient satisfaction. PLoS One 2013;8:e76121. 9. Uchino M, Nishiwaki Y, Michikawa T, et al. Prevalence and risk factors of dry eye disease in Japan: Koumi study. Ophthalmology. 2011;118: 2361–2367. 10. Pflugfelder SC, Solomon A, Stern ME. The diagnosis and management of dry eye: a twenty-five-year review. Cornea. 2000;19:644–649. 11. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea. 2004;23: 762–770. 12. Johnson ME. The association between symptoms of discomfort and signs in dry eye. Ocul Surf. 2009;7:199–211. 13. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5:93–107. 14. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25: 900–907. 15. Chalmers RL, Begley CG, Edrington T, et al. The agreement between self-assessment and clinician assessment of dry eye severity. Cornea. 2005;24:804–810. 16. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003;22:640–650.
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17. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118:615–621. 18. Li M, Gong L, Chapin WJ, et al. Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci. 2012;53:5722–5727. 19. Miller KL, Walt JG, Mink DR, et al. Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmol. 2010; 128:94–101. 20. Claramita M, Nugraheni MD, van Dalen J, et al. Doctor-patient communication in Southeast Asia: a different culture? Adv Health Sci Educ Theory Pract. 2013;18:15–31. 21. Song JS, Hyon JY, Lee D, et al. Current practice pattern for dry eye patients in South Korea: a multicenter study. Korean J Ophthalmol. 2014;28:115–121. 22. Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51:6125–6130. 23. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011;151:792– 798.e1. 24. Foulks GN, Pflugfelder SC. New testing options for diagnosing and grading dry eye disease. Am J Ophthalmol. 2014;157:1122–1129. 25. Sullivan BD, Crews LA, Messmer EM, et al. Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications. Acta Ophthalmol. 2014;92:161–166. 26. Begley CG, Chalmers RL, Abetz L, et al. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci. 2003;44: 4753–4761. 27. Lin PY, Cheng CY, Hsu WM, et al. Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Invest Ophthalmol Vis Sci. 2005;46:1593–1598. 28. Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain: is it real? Ocul Surf. 2009;7:28–40. 29. Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf. 2012;10:2–14. 30. Chao C, Golebiowski B, Stapleton F. The role of corneal innervation in LASIK-induced neuropathic dry eye. Ocul Surf. 2014;12:32–45. 31. Grubbs JR Jr, Tolleson-Rinehart S, Huynh K, et al. A review of quality of life measures in dry eye questionnaires. Cornea. 2014;33:215–218. 32. Sullivan B. Challenges in using signs and symptoms to evaluate new biomarkers of dry eye disease. Ocul Surf. 2014;12:2–9. 33. Bron AJ, Tomlinson A, Foulks GN, et al. Rethinking dry eye disease: a perspective on clinical implications. Ocul Surf. 2014;12:S1–S31. 34. Turner AW, Layton CJ, Bron AJ. Survey of eye practitioners’ attitudes towards diagnostic tests and therapies for dry eye disease. Clin Experiment Ophthalmol. 2005;33:351–355.
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