Title:
Computer simulation of progressive retinal nerve fiber layer loss in glaucoma: performance of event and trend analyses.

Abstract:
Although event analysis (EA) and trend analysis (TA) have been widely adopted to evaluate glaucoma progression in clinical trials, there is poor agreement between the strategies and no consensus on strategy selection in clinical practice. With computer simulation of progressive loss of the retinal nerve fiber layer (RNFL), the authors compared the performance of TA and EA for the detection of glaucoma progression.
RNFL progression was modeled with reference to the individual's test-retest variability and the pattern and rate of progression. The sensitivity and specificity of each scenario were computed from 5000 simulated datasets. Simulation results were validated with longitudinal RNFL measurements obtained from 107 glaucoma and glaucoma suspect patients who had a median follow-up period of 38 months.
TA generally attained a sensitivity ≥80% earlier than EA, although EA with a group reproducibility coefficient had a higher sensitivity than TA for eyes with a large test-retest variability in the early follow-up period, albeit at a lower specificity. The specificity of TA was 95% and ranged between 80% and 100% for EA. Independent of test-retest variability and the pattern and rate of progression, TA had an accuracy ≥80% earlier than EA. In the longitudinal study, the detection rate was 42%, 35%, and 3% for TA, whereas it was 11% to 40%, 12% to 28%, and 3% to 23% for EA at 36 months of follow-up in eyes with small, average, and large test-retest variabilities, respectively.
Although test-retest variability is an important determinant in progression analysis, TA generally outperformed EA for the detection of RNFL progression in glaucoma.