1. Vatinee Y. Bunya, MD, Mina Massaro-Giordano, MD, Frederick B. Vivino, MD*, Stephen E. Orlin, MD, Michael E. Sulewski, MD, and Maureen G. Maguire, PhD The authors are receiving research supplies from TearLab for a separate study. Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA * Division of Rheumatology, Penn Presbyterian Medical Center, Philadelphia, PA

2. Purpose To study tear film osmolarity in Sjogren’s syndrome patients To assess if tear film osmolarity in Sjogren’s syndrome patients is correlated with symptoms (OSDI) or unanesthetized Schirmer testing To compare patient discomfort associated with tear osmolarity testing to unanesthetized Schirmer testing

3. Methods Prospective study to evaluate the tear film osmolarity of Sjogren’s syndrome patients Demographic information and medication usage was recorded Tear film osmolarity: TearLab osmolarity system System calibrated daily as specified by manufacturer Unanesthetized Schirmer testing Patient-reported pain scores (0-5 with 5 = severe pain) after tear osmolarity and Schirmer testing OSDI self-administered Spearman (non-parametric) correlation coefficients used due to small sample size

4. Age Mean (Std), yrs55.7 (15.5) Range18-88 Sex Male1 (5%) Female19 (95%) Race/Ethnicity White13 (65%) African-American6 (30%) Hispanic1 (5%) Sjogren’s Syndrome Primary16 (80%) Secondary4 (20%) Results

5. Systemic Medications Hydroxychloroquine (Plaquenil)12 (63%) Pilocarpine (Salagen)12 (63%) Fish oil (not Lovaza)11 (58%) Omega-3-acid ethyl esters (Lovaza)3 (16%) Flaxseed6 (32%) Prednisone (oral)6 (32%) Methotrexate4 (21%) Azathioprine (Imuran)2 (11%) Rituximab (Rituxan)1 (6%) Eye Medications Cyclosporine (Restasis)5 (26%) Erythromycin Ointment2 (11%) * 1 patient did not provide a medication list Medication Use

6. Results Average OSDI score: 46.6 Average tear osmolarity: 311 mOsmol/L Average unanesthetized Schirmer score: 13 mm/5 min Median pain scores Tear osmolarity testing: 1 Unanesthetized Schirmer testing: 4 p < 0.001 (Wilcoxon signed rank test)

7. OSDI does not correlate well with unanesthetized Schirmer score (averaged between eyes).

8. OSDI correlates well with tear osmolarity (averaged between eyes).

9. Average unanesthetized Schirmer score does not correlate with average tear osmolarity. r= - 0.14 p= 0.56

10. Previous studies have suggested that tear film osmolarity may be the single best test in the diagnosis of dry eye. 1, 2 To our knowledge, tear osmolarity has not been studied specifically in Sjogren’s syndrome patients. In our study, the average tear osmolarity was 311 mOsmol/L. This is lower than the referent of 316 mOsmol/L. 1 This is most likely due to the fact that 95% of our patients were on treatment at the time of the study. We would expect the tear osmolarity to be higher in untreated patients.

11. Tear osmolarity correlated with patient symptoms while unanesthetized Schirmer testing did not. Tear osmolarity did not correlate with unanesthetized Schirmer scores. In addition, pain scores associated with osmolarity testing were lower than for unanesthetized Schirmer testing. Tear osmolarity testing may be superior to Schirmer testing to follow dry eye disease in patients with Sjogren’s syndrome. Future larger studies would be needed to confirm this hypothesis.

12. 1. Tomlinson A, Khanal S, Ramaesh K, Diaper C, et al. Tear film osmolarity: Determination of a Referent for Dry Eye Diagnosis. Invest Ophthalmol Vis Sci 2006; 47:4309-15. 2. Khanal S, Tomlinson A, McFadyen A, Diaper C, et al. Dry Eye Diagnosis. Invest Ophthalmol Vis Sci 2008; 49:1407-14.