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Benjamin D. Sullivan, Baris Sonmez, María F. de la Paz, Michael S. Berg, Michael A. Lemp; Longitudinal Variability Of Biomarkers for Dry Eye Disease - Implications for Clinical Trials. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3804.
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The purpose of this study was to evaluate normative statistics of biomarkers for dry eye disease over time periods typical of clinical trials. An additional therapeutic arm continued to follow a subset of patients on Restasis therapy to determine the comparative efficacy of signs in measuring treatment effect.
Bilateral tear film breakup time (TBUT), Schirmers, staining, meibomian gland grading, OSDI, and tear osmolarity were measured over three consecutive months. 52 subjects completed the study across two sites (n=16 mild/moderate, n=36 severe dry eye). 10 subjects were prescribed Restasis and signs were recorded for an additional three months. To compare variability, the average observed range (as defined by the difference of maximum and minimum values of the more severe eye across all three visits) was calculated as a percentage of the dynamic range for each marker.
Tear osmolarity (16.7±12.2%) was found to have significantly less variability over three months than TBUT (30.2±26.1%, p<0.001), Schirmers (30.6±26.5%, p<0.001), meibomain gland scoring (26.5±16.5%, p<0.001) and OSDI (24.8±18.4%, p<0.01). Across all subjects, there was no difference between osmolarity and corneal (12.6±15.3%, p<0.14) or conjunctival (15.4±17.9%, p<0.67) staining. However, the majority of subjects at one site (20/31) demonstrated zero staining, artificially lowering its average variability. Osmolarity variation was significantly less in mild patients (11±6%) than in severe patients (19±13%, p<0.03). For subjects enrolled in the therapeutic arm, the average pretreatment osmolarity was significantly reduced from 341±18 mOsms/L to 307±8 mOsms/L (p=0.000002), while OSDI was significantly reduced from 51±18 to 38±18 (p=0.04). None of the other signs demonstrated a significant change in response to treatment.
The longitudinal variability of tear film osmolarity is significantly less than the other biomarkers of dry eye disease. Changes in osmolarity were paralleled by changes in symptoms during therapy.
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