Abstract
OBJECTIVE
To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren's syndrome (SS) work-up.
METHODS
An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data.
RESULTS
474 survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The most common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%).
Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS work-ups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS.
CONCLUSIONS
Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an under-referral of dry eye patients for SS work-ups, which is contributing to the continued underdiagnosis of the disease. The majority of respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.
Keywords: survey, dry eye practice patterns, dry eye disease, Sjogren's syndrome
Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film that results in symptoms of discomfort, pain and visual disturbances that significantly affect quality of life1, 2. Tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities play etiological roles in DED.2 It is highly prevalent, and is one of the most common reasons that patients seek care from an ophthalmologist3, affecting up to 50% of adults.4
There currently is no gold standard test for diagnosing DED, and as a result a variety of diagnostic tests are utilized. Traditional tests include ocular surface staining with a variety of vital dyes, tear break-up time, and Schirmer testing.5 In recent years, newer tests have become available including tear osmolarity testing, MMP-9 testing, and various methods to image the tear film and meibomian glands5, 6. However, it is unknown how the introduction of these new testing modalities has influenced the way ophthalmologists evaluate DED patients.
In addition, a subset of DED patients have underlying Sjogren's syndrome (SS), a chronic, debilitating, and potentially deadly autoimmune disease which is characterized by irreversible damage to the lacrimal glands and salivary glands with a loss of tear and saliva production, leading to a significant reduction in quality of life.7–9 The disease is also associated with autoantibody production, systemic complications, and an almost 20-fold higher risk of lymphoma that increases with disease duration.10 Lacrimal gland involvement in SS often leads to aqueous deficient dry eye, which is classically associated with a marked decrease in tear production and severe ocular surface inflammation.11 SS is estimated to affect between 2 to 4 million Americans, with half of SS patients remaining undiagnosed due to the nonspecific nature of early clinical manifestations and an average delay in diagnosis of up to 7 years from the onset of symptoms11–13.
The diagnosis of SS is complex and requires collaboration among multiple subspecialists including ophthalmology, rheumatology, and oral medicine. Several different sets of classification criteria for SS have been proposed. One of the more commonly used classification criteria sets is the American European Consensus Group (AECG) criteria. The AECG set of criteria includes both symptoms and signs of DED (Schirmer without anesthesia of ≤5 mm/5 min or vital dye staining of the ocular surface ≥4 van Bijsterveld scoring system).8 In 2012, the American College of Rheumatology (ACR)/Sjogren's International Collaborative Clinical Alliance (SICCA) criteria were proposed that no longer included subjective symptoms and only included objective signs.14 Finally, more recently, the ACR-EULAR criteria were proposed which contains elements of both the AECG and ACR/SICCA criteria.15
Because SS patients often have DED, they frequently first seek care from an ophthalmologist, who is in a position to facilitate early referrals for work-ups for SS. However, it is unclear which symptoms and signs ophthalmologists currently use when deciding whether or not to refer a dry eye patient for a SS work-up, or how often dry eye patients are being referred for evaluations. Early diagnosis and management are essential for the optimal management of SS to improve quality of life and to monitor patients for the development of systemic complications such as lymphoma11.
The diagnosis of SS is hampered by significant limitations of sensitivity and specificity of traditional autoantibodies with an established link to SS16, 17. While Sjogren's Syndrome A (SSA/Ro) and Sjogren's Syndrome B (SSB/La) antibodies are traditionally described as the hallmark antibodies of SS and are included in the diagnostic criteria for SS, they are only found in 60–70% of SS patients presenting to rheumatology clinics 18. Recently, new candidate SS antibodies were described in a mouse model for SS19 and are commercially available in the "Sjo" finger stick kit performed in the office or as a blood draw (Bausch & Lomb, Rochester, NY). However, it is unclear how many ophthalmologists are currently aware of this kit and how many are using it in their practice or are ordering this blood test.
Currently there is no standardized approach to DED patients regarding ophthalmologic evaluation or referral of patients for a SS work-up. Therefore, our goal was to survey ophthalmologists to assess current practice patterns regarding the evaluation of DED patients and referrals for SS work-ups.
Methods
In August 2015, we conducted an online survey of ophthalmologists using REDCap.com, a secure web application that can be used to build and manage online survey and databases20. The survey invitation was sent to 474 ophthalmologists from across the country who are or were affiliated with the Scheie Eye Institute or Wills Eye Hospital. The questionnaire created for this study was designed to assess each ophthalmologist’s practice patterns regarding dry eye patients and referrals for evaluations for SS and has not previously been validated (see Supplemental Digital Content). The survey included questions regarding the ophthalmologists’ specialties, practice setting, and dry eye patient populations. Ophthalmologists were also asked about their knowledge and preferences regarding dry eye testing in their offices, as well as about the use of standardized dry eye grading scales. The surveyed ophthalmologists were asked to rank their top 3 traditional dry eye tests from the following tests: fluorescein staining of the cornea, tear break-up time, lissamine green staining of the conjunctiva, rose bengal staining of the conjunctiva, and Schirmer test (unanesthetized or anesthetized). Similarly, they were asked to rank their top 3 newer dry eye tests from the following tests: tear osmolarity assessment, MMP-9 testing with InflammaDry® (RPS Diagnostics, Sarasota, FL), Lipiview® (TearScience, Morrisville, NC), optical coherence tomography of tear film, and meibography. The survey also included questions regarding their general knowledge about SS, the Sjo test (Bausch & Lomb, Rochester, NY), as well as referral patterns and testing of dry eye patients with suspected SS. Ophthalmologists were asked to respond the survey questions through the Redcap.com web application.
Statistical Analysis
We performed descriptive analyses of this survey data by calculating the percentage of respondents with a response in a particular category. We compared survey responses between ophthalmologists in academic practices vs. non-academic practices, and between cornea specialists vs. non-cornea specialists using the Fisher exact test. All the statistical analyses were performed using SAS v9.4 (SAS Institute Inc., NC, Cary).
Results
Of the 474 survey invitations sent out, 101 (21.3%) ophthalmologists responded and completed the survey. The characteristics of survey respondents are shown in Table 1. The majority of the respondents were cornea specialists (42.6%), followed by comprehensive ophthalmologists (20.8%). Over half of respondents were in full-time private practice (56.4%), with about one-third practicing full-time in an academic institution (35.6%). Overall, there were no statistically significant differences in the responses of physicians in academic versus non-academic settings (all p>0.11). The majority (78.2%) of respondents had been in practice for more than 5 years. Overall, more than half (60.4%) of the participants reported that dry eye patients make up about 20–60% of their practice, and that they spent on average 5 minutes or less performing a dry eye examination in the office.
Table 1.
Characteristics of survey respondents (n=101)
| Characteristics of survey respondents | n (%) |
|---|---|
| Sub-specialty | |
| Cornea | 43 (42.6%) |
| Glaucoma | 5 (5.0%) |
| Neuro-ophthalmology | 4 (4.0%) |
| Oculoplastics | 4 (4.0%) |
| Pediatric ophthalmology | 10 (9.9%) |
| Retina | 14 (13.9%) |
| No subspecialty listed | 21 (20.8%) |
| Setting of practice | |
| Academic | 36 (35.6%) |
| Equal time in academic and private practice | 7 (6.9%) |
| Private practice | 57 (56.4%) |
| Unknown | 1 (1.0%) |
| Years in practice | |
| 2 years or less | 10 (9.9%) |
| 2–5 years | 12 (11.9%) |
| 5–10 years | 21 (20.8%) |
| 10–20 years | 24 (23.8%) |
| 20 years or more | 28 (27.7%) |
| Unknown | 6 (5.9%) |
| Percent of patients in practice with dry eye | |
| 0–20% | 25 (24.8%) |
| 20–40% | 38 (37.6%) |
| 40–60% | 23 (22.8%) |
| 60–80% | 10 (9.9%) |
| >80% | 3 (3.0%) |
| Not applicable | 2 (2.0%) |
| Length of time typically spent performing dry eye examination in the office | |
| 30 seconds or less | 13 (12.9%) |
| 30–60 seconds | 20 (19.8%) |
| 1–3 minutes | 23 (22.8%) |
| 3–5 minutes | 23 (22.8%) |
| More than 5 minutes | 19 (18.8%) |
| Not applicable | 3 (3.0%) |
Dry Eye Tests
The results of the ranking of top 3 traditional dry eye tests and top 3 newer dry eye tests are shown in Table 2. The majority of participants reported that they more frequently used traditional dry eye tests compared to newer tests in the office. The most common traditional dry eye tests performed were corneal fluorescein staining (ranked as most common by 62%), tear break-up time (49%) and anesthetized Schirmer’s test (32%). Among the newer diagnostic tests, tear osmolarity assessment was the most frequently test used, with 18% ranking this as most commonly used newer test used.
Table 2.
Top 3 most commonly used traditional and newer dry eye tests done in the office as rated by survey respondents. Respondents ranked their top 3 choices from each list.
| Percent selected as top 1, 2, 3 for each dry eye test | ||||
|---|---|---|---|---|
| Traditional dry eye tests | Top 1 | Top 2 | Top 3 | Top 1, 2, 3 combined |
| Fluorescein staining of the cornea | 63 (62.4%) | 21 (20.8%) | 6 (5.9%) | 90 (89.1%) |
| Tear break-up time (TBUT) | 19 (18.8%) | 49 (48.5%) | 11 (10.9%) | 79 (78.2%) |
| Lissamine green staining of the conjunctiva | 6 (5.9%) | 7 (6.9%) | 12 (11.9%) | 25 (24.8%) |
| Rose bengal staining of the conjunctiva | 2 (2.0%) | 3 (3.0%) | 8 (7.9%) | 13 (12.9%) |
| Schirmer test - unanesthetized | 4 (4.0%) | 7 (6.9%) | 11 (10.9%) | 22 (21.8%) |
| Schirmer test - anesthetized | 5 (5.0%) | 14(13.9%) | 32 (31.7%) | 51 (50.5%) |
| Newer dry eye tests | ||||
| Tear osmolarity | 18 (17.8%) | 2 (2.0%) | 3 (3.0%) | 23 (22.8%) |
| InflammaDry® (MMP-9) | 6 (5.9%) | 8 (7.9%) | 3 (3.0%) | 17 (16.8%) |
| Lipiview® | 3 (3.0%) | 8 (7.9%) | 2 (2.0%) | 13 (12.9%) |
| Optical coherence tomography of tear film | 4 (4.0%) | 0 (0.0%) | 2 (2.0%) | 6 (5.8%) |
| Meibography | 2 (2.0%) | 1 (1.0%) | 2 (2.0%) | 5 (4.9%) |
TBUT =Tear Break up; MMP-9=Matrix Metalloproteinase 9
Dry Eye Grading Scales
The majority of the respondents (82.2%) reported that they do not routinely use a standard DED severity grading scale. About half of the respondents (51.5%) were familiar with the Dry Eye Workshop (DEWS) dry eye severity grading scale1; however among those familiar with the scale, only 19% (n=10) use it routinely in their offices. Most (57.1%) of those who do not routinely use the scale feel it takes too long to use in the office. Only a quarter of respondents (25.7%) were familiar with the Sjogren’s International Collaborative Clinical Alliance (SICCA) Ocular Staining Score (OSS) grading scale21 and among those who were familiar, only about a quarter (23%, n=6) use it routinely in their offices. Those who do not use the OSS grading routinely felt it either takes too long (42.1%) or is not clinically useful (47.4%)
Sjogren's Syndrome
Table 3 summarizes the responses to questions about SS. Half of respondents (50.5%) reported that they refer fewer than 5% of their dry eye patients for SS work-ups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60.4%) (most common extraocular symptom: dry mouth), severe dry eye symptoms (50.5%) or signs (46.5%), or dry eye that is refractory to treatment (41.6%). The most common ocular signs that would cause referral for SS workup were severe corneal staining (59.4%), unanesthetized Schirmer’s score of <5mm (37.6%) and severe conjunctival lissamine green staining (28.7%). Approximately two-thirds (67%) of respondents were not familiar with either one of the two current sets of classification criteria for SS available at the time of the survey, specifically the American-European Consensus Group Criteria (AECG)8 and the American College of Rheumatology/Sjogren’s International Collaborative Clinical Alliance Criteria (ACR/SICCA)14.
Table 3.
Ophthalmologist responses regarding Sjogren’s syndrome (SS) management and referral patterns
| Questions regarding Sjogren's Syndrome (SS) | n (%) |
|---|---|
| Percent of dry eye patients referred to a rheumatologist for a SS work-up | |
| None | 18 (17.8%) |
| <5% | 51 (50.5%) |
| 5–10% | 18 (17.8%) |
| >10% | 10 (10.0%) |
| Unknown | 4 (4.0%) |
| Common reasons for referral of dry eye patients for SS work-up (check all that apply) | |
| Positive review of systems | 61 (60.4%) |
| Severe dry eye symptoms | 51 (50.5%) |
| Ocular signs consistent with severe dry eye | 47 (46.5%) |
| Refractory to dry eye treatment | 42 (41.6%) |
| Other disease | 5 (5.0%) |
| None of the above | 4 (4.0%) |
| Not applicable | 12 (11.9%) |
| Extra-ocular symptoms routinely asked about when trying to decide when to refer a dry eye patient for a SS work-up (check all that apply) | |
| Dry mouth | 82 (81.2%) |
| Frequent dental problems/cavities | 25 (24.8%) |
| Dry nose | 16 (15.8%) |
| Joint pain | 53 (52.5%) |
| Joint swelling | 37 (36.6%) |
| Dry skin | 24 (23.8%) |
| Constipation | 3 (3.0%) |
| Vaginal dryness | 13 (12.9%) |
| Rash | 11 (10.9%) |
| Other | 1 (1.0%) |
| Not applicable | 13 (12.9%) |
| Ocular signs that would cause referral of dry eye patients for SS work-up (check all that apply) | |
| Moderate corneal fluorescein staining | 7 (6.9%) |
| Severe corneal fluorescein staining | 60 (59.4%) |
| Moderate lissamine green staining of conjunctiva | 16 (15.8%) |
| Severe lissamine green staining of conjunctiva | 29 (28.7%) |
| Schirmer test <8 mm/min | 6 (5.9%) |
| Schirmer test <5 mm/min | 38 (37.6%) |
| Other | 3 (3.0%) |
| None of the above | 9 (8.9%) |
| Not applicable | 14 (13.9%) |
| Do you think there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred to a rheumatologist for a SS work-up? | |
| No | 14 (13.9%) |
| Yes | 84 (83.2%) |
| Unknown | 3 (3.0%) |
| Have you heard of Sjo test? | |
| No | 54 (53.5%) |
| Yes | 41 (40.6%) |
| Unknown | 6 (5.9%) |
SS= Sjogren's syndrome
Over half of respondents (53.5%) had never heard of the Sjo test. Of those who were familiar with it, only 7% of ophthalmologists were routinely checking this test on their dry eye patients. 93% of respondents were unsure how the Sjo test results would guide their management of patients. The overwhelming majority of respondents (83%) felt that there was a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS.
When comparing referral patterns for SS workups and between cornea and non-cornea specialists (Table 4), cornea specialists reported referring patients more often to a rheumatologist (100% vs. 66.7% for referring at least 5%, p <0.0001, Fisher exact test) or ordering blood work for SS antibodies (79.1% vs. 40.7% for ordering at least 5%, p <0.0001, Fisher exact test) compared to non-cornea specialists. Cornea specialists were also more commonly familiar with the DEWS dry eye severity grading scale than non-cornea specialists (43.9% vs. 17.0%, p=0.006, Fisher exact test).
Table 4.
Comparison of survey responses between cornea and non-cornea specialists
| Non-cornea specialists (n=58) |
Cornea specialists (n=43) |
Fisher exact P-value |
|
|---|---|---|---|
| Percent of dry eye patients referred to a rheumatologist for a SS work-up | <0.0001 | ||
| None | 18 (33.3%) | 0 (0.0%) | |
| <5% | 32 (59.3%) | 19 (44.2%) | |
| ≥5% | 4 (7.5%) | 24 (55.8%) | |
| Do you think there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred to a rheumatologist for a SS work-up? | 1.00 | ||
| No | 8 (14.6%) | 6 (14.0%) | |
| Yes | 47 (85.5%) | 37 (86.1%) | |
| Percent of dry eye patients in whom you order blood-work for traditional antibodies looking for SS | <0.0001 | ||
| None | 32 (59.3%) | 9 (20.9%) | |
| <5% | 16 (29.6%) | 13 (30.2%) | |
| ≥5% | 6 (11.1%) | 21 (48.8%) | |
| Are you familiar with the 2 current sets of diagnostic criteria for Sjogren’s syndrome (AECG and ACR/SICCA criteria)? | 0.006 | ||
| No | 44 (83.0%) | 23 (56.1%) | |
| Yes | 9 (17.0%) | 18 (43.9%) | |
| Have you heard of the Sjo test? | <0.0001 | ||
| No | 40 (75.5%) | 14 (33.3%) | |
| Yes | 13 (24.5%) | 28 (66.7%) | |
| Are you familiar with Dry Eye WorkShop (DEWS) severity grading scale? | <0.0001 | ||
| No | 41 (75.9%) | 2 (4.9%) | |
| Yes | 13 (24.1%) | 39 (95.1%) | |
| Are you familiar with the Ocular Staining Score (OSS)? | 0.002 | ||
| No | 46 (85.2%) | 23 (56.1%) | |
| Yes | 8 (14.8%) | 18 (43.9%) |
Discussion
Our study survey provides insight into how ophthalmologists currently approach patients with DED. Our results can be compared to a survey done in 2000 by Korb in which he surveyed 36 optometrists and 41 ophthalmologists nationally and internationally with a background in dry eye about their preferred test22. In contrast to that study, our survey included 101 ophthalmologists in the United States who are comprehensive ophthalmologists and subspecialists. Similar to the study conducted by Korb22 fifteen years ago, we found that ophthalmologists in our survey still prefer using traditional dry eye tests despite the increased availability of newer in-office DED tests. However, in contrast to Korb's study in which there was no clear top choice of DED test, our study found over half of ophthalmologists reported that corneal staining with fluorescein as the most common test for the evaluation of DED patients. Also consistent with previous reports, conjunctival staining with lissamine green is not frequently used in DED evaluations, despite the fact that conjunctival staining with lissamine green is an integral part of the DEWS severity grading scale and the OSS scale that is part of the ocular classification criteria for SS. Therefore, it is critical that ophthalmologists perform conjunctival staining with lissamine green, in addition to corneal staining with fluorescein.
Lissamine green staining of the conjunctiva is included in both the DEWS severity scale and OSS scale. Dry eye severity scales help stratify and categorize patients’ dry eye disease, and can be useful in monitoring treatment response. However, our study found a low level of familiarity with the use of these grading scales, and the majority of our respondents felt that these scales either took too long or were not clinically useful. Our study found that only a quarter of respondents were familiar with the SICCA OSS grading scale21 and among those who were familiar, only about a quarter (23%, n=6) use it routinely in their offices. The OSS scale was proposed by the SICCA group to develop a standardized method for evaluating for ocular involvement in Sjogren’s syndrome21, and is a part of the American College of Rheumatology (ACR)/SICCA criteria and also the more recently approved ACR/European League Against Rheumatism (EULAR) classification criteria for SS.15 The OSS scale is composed of scores from corneal staining with fluorescein as well as conjunctival staining with lissamine green. The OSS score is calculated by the summation of the fluorescein score for the cornea and the lissamine green scores for the nasal and temporal bulbar conjunctiva; with additional points given for the presence of central corneal staining, confluence, or the presence of filaments21. Therefore, in order to assess patients for the ocular classification criteria for SS, the ocular surface must be assessed using the OSS grading scale. Increased awareness and utilization of the OSS grading scale is needed so that dry eye patients can be properly evaluated for possible SS.
In our study, we found that the most common reasons for SS referrals included positive review of systems (most common extraocular symptom: dry mouth) and the presence of severe corneal staining. Overall there was a low referral rate of dry eye patients for SS evaluations with half of respondents reporting that they refer less than 5% of their dry eye patients for SS work-ups, and about 1 in 5 reporting that they never refer any patients. There appear to be several contributing factors to this low referral rate. Approximately two-thirds of respondents were not familiar with either one of the two current sets of classification criteria for SS available at the time of the survey. We found that the majority of ophthalmologists in our survey felt that there is a need for a standardized approach to dry eye evaluation and tools for screening those who warrant referral for SS workups. An increased awareness and familiarity with the SS classification criteria and the OSS grading scale, as well as the development of a standardized screening tool could increase referrals of dry eye patients for SS evaluations.
Over half of respondents had never heard of the Sjo test, and of those who were familiar with the test, the majority were unsure how the results affect their management. Further studies regarding the interpretation and clinical meaning of the Sjo test results would be helpful and may increase use of this test by ophthalmologists.
Finally, we found that many ophthalmologists have been slow to adopt newer dry eye tests into practice and most continue to rely on traditional in-office dry eye examinations. Newer diagnostic modalities in dry eye, such as tear osmolarity assessment, determination of surface inflammatory markers (e.g. matrix metalloproteinase 9) by using in-office rapid screening kits, Lipiview® and meibography, are available adjunctive tests for the evaluation of DED. It is possible that the hesitation to implement these tests in the office is due to the lack of evidence that show an additional benefit to the evaluation of DED patients over traditional tests.23
Our study had certain limitations. For example, our survey did not include questions about all possible biomarkers for SS such as HLA-DR or cytokines. However, because the Sjo kit is currently available and marketed to ophthalmologists we chose to focus on assessing knowledge about those antibody tests. Future surveys that include other SS biomarkers would be helpful. In addition, our sample size was limited in that 101 ophthalmologists responded to the survey. However, this response rate is similar or higher than that of other previously published survey studies24, 25, and a strength of our study was that it included cornea specialists as well as non-cornea specialists. Finally, our study was only sent to ophthalmologists and did not include other eye care providers such as optometrists. In the future, we plan to survey a broader range of eye care providers to increase the generalizability of our findings.
Conclusions
Despite the introduction of several new diagnostic dry eye tests in recent years, we found that ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There continues to be an under-referral of dry eye patients for SS work-ups, which is contributing to the continued under-diagnosis of the disease. This under-referral could partly be due to a lack of familiarity with the OSS grading scale used to evaluate patients for the ocular criteria for SS. The overwhelming majority of ophthalmologists in our study felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for SS evaluation. An increased knowledge of the SS classification criteria and the development of improved standardized screening tools could help in the optimization of timely evaluations for SS, leading to earlier diagnosis and better outcomes.
Supplementary Material
Supplemental Digital Content Legend: A copy of the questionnaire that was used in the survey.
Acknowledgments
Funding:
Vatinee Y. Bunya is supported by the National Eye Institute R01-EY026972 and Research to Prevent Blindness. Gui-shuang Ying is supported by the National Eye Institute P30 EY01583-26. Mina Massaro-Giordano is supported by Research to Prevent Blindness.
Footnotes
Financial Disclosures/Conflict of Interest Statement:
Vatinee Y. Bunya received a grant from Bausch & Lomb for an unrelated study. Gui-shuang Ying serves as a consultant for Janssen R & D and Kanghong Biotech Inc. Mina Massaro-Giordano serves as a consultant for Glaxo Smith Kline, and is an investor in PRN. Kristin M. Hammersmith serves on the speaker's bureau for Shire. Christopher J. Rapuano serves as a consultant for Aerie, Allergan, and TearLab. He also is on the speaker's bureau and is a consultant for Bausch & Lomb, Bio-Tissue, and Shire. For the remaining authors none were declared.
This work was presented in a poster presentation at ARVO, May 9, 2017, Baltimore, Maryland.
References
- 1.The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007) Ocul Surf. 2007;5(2):75–92. doi: 10.1016/s1542-0124(12)70081-2. [DOI] [PubMed] [Google Scholar]
- 2.Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276–83. doi: 10.1016/j.jtos.2017.05.008. [DOI] [PubMed] [Google Scholar]
- 3.Barabino S, Labetoulle M, Rolando M, Messmer EM. Understanding Symptoms and Quality of Life in Patients With Dry Eye Syndrome. Ocul Surf. 2016;14(3):365–76. doi: 10.1016/j.jtos.2016.04.005. [DOI] [PubMed] [Google Scholar]
- 4.Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017;15(3):334–65. doi: 10.1016/j.jtos.2017.05.003. [DOI] [PubMed] [Google Scholar]
- 5.Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017;15(3):539–74. doi: 10.1016/j.jtos.2017.05.001. [DOI] [PubMed] [Google Scholar]
- 6.McGinnigle S, Naroo SA, Eperjesi F. Evaluation of dry eye. Surv Ophthalmol. 2012;57(4):293–316. doi: 10.1016/j.survophthal.2011.11.003. [DOI] [PubMed] [Google Scholar]
- 7.Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ. 2012;344:e3821. doi: 10.1136/bmj.e3821. [DOI] [PubMed] [Google Scholar]
- 8.Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554–8. doi: 10.1136/ard.61.6.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Segal B, Bowman SJ, Fox PC, et al. Primary Sjogren's Syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes. 2009;7:46. doi: 10.1186/1477-7525-7-46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165(20):2337–44. doi: 10.1001/archinte.165.20.2337. [DOI] [PubMed] [Google Scholar]
- 11.Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med. 2004;164(12):1275–84. doi: 10.1001/archinte.164.12.1275. [DOI] [PubMed] [Google Scholar]
- 12.Kruszka P, O'Brian RJ. Diagnosis and management of Sjogren syndrome. Am Fam Physician. 2009;79(6):465–70. [PubMed] [Google Scholar]
- 13.Manthorpe R, Asmussen K, Oxholm P. Primary Sjogren's syndrome: diagnostic criteria, clinical features, and disease activity. J Rheumatol Suppl. 1997;50:8–11. [PubMed] [Google Scholar]
- 14.Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64(4):475–87. doi: 10.1002/acr.21591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjogren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017;69(1):35–45. doi: 10.1002/art.39859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Tincani A, Andreoli L, Cavazzana I, et al. Novel aspects of Sjogren's syndrome in 2012. BMC Med. 2013;11:93. doi: 10.1186/1741-7015-11-93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Goeb V, Salle V, Duhaut P, et al. Clinical significance of autoantibodies recognizing Sjogren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjogren's syndrome. Clin Exp Immunol. 2007;148(2):281–7. doi: 10.1111/j.1365-2249.2007.03337.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Hernandez-Molina G, Leal-Alegre G, Michel-Peregrina M. The meaning of anti-Ro and anti-La antibodies in primary Sjogren's syndrome. Autoimmun Rev. 2011;10(3):123–5. doi: 10.1016/j.autrev.2010.09.001. [DOI] [PubMed] [Google Scholar]
- 19.Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjogren's syndrome. Clin Immunol. 2012;145(3):251–5. doi: 10.1016/j.clim.2012.09.013. [DOI] [PubMed] [Google Scholar]
- 20.Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. doi: 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Whitcher JP, Shiboski CH, Shiboski SC, et al. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren's Syndrome International Registry. Am J Ophthalmol. 2010;149(3):405–15. doi: 10.1016/j.ajo.2009.09.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Korb DR. Survey of preferred tests for diagnosis of the tear film and dry eye. Cornea. 2000;19(4):483–6. doi: 10.1097/00003226-200007000-00016. [DOI] [PubMed] [Google Scholar]
- 23.Kuklinski E, Asbell PA. Sjogren's syndrome from the perspective of ophthalmology. Clin Immunol. 2017 doi: 10.1016/j.clim.2017.04.017. [DOI] [PubMed] [Google Scholar]
- 24.Asbell PA, Spiegel S. Ophthalmologist perceptions regarding treatment of moderate-to-severe dry eye: results of a physician survey. Eye Contact Lens. 2010;36(1):33–8. doi: 10.1097/ICL.0b013e3181c739ad. [DOI] [PubMed] [Google Scholar]
- 25.Williamson JF, Huynh K, Weaver MA, Davis RM. Perceptions of dry eye disease management in current clinical practice. Eye Contact Lens. 2014;40(2):111–5. doi: 10.1097/ICL.0000000000000020. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Supplemental Digital Content Legend: A copy of the questionnaire that was used in the survey.