Comparing the Rule of 5 to Trend-based Analysis for Detecting Glaucoma Progression on OCT.

Purpose: The rule of 5 is a simple rule for detecting retinal nerve fiber layer (RNFL) change on spectral-domain OCT (SD-OCT), in which a loss of 5 μm of global RNFL on a follow-up test is considered evidence of significant change when compared with the baseline. The rule is based on short-term test-retest variability of SD-OCT and is often used in clinical practice. The purpose of this study was to compare the rule of 5 with trend-based analysis of global RNFL thickness over time for detecting glaucomatous progression.

Design: Prospective cohort.

Participants: A total of 300 eyes of 210 glaucoma subjects followed for an average of 5.4±1.5 years with a median of 11 (interquartile range, 7-14) visits.

Methods: Trend-based analysis was performed by ordinary least-squares (OLS) linear regression of global RNFL thickness over time. For estimation of specificity, false-positives were obtained by assessing for progression on series of randomly permutated follow-up visits for each eye, which removes any systematic trend over time. The specificity of trend-based analysis was matched to that of the rule of 5 to allow meaningful comparison of the "hit rate," or the proportion of glaucoma eyes categorized as progressing at each time point, using the original sequence of visits.

Main Outcome Measures: Comparison between hit rates of trend-analysis versus rule of 5 at matched specificity.

Results: After 5 years, the simple rule of 5 identified 37.5% of eyes as progressing at a specificity of 81.1%. At the same specificity, the hit rate for trend-based analysis was significantly greater than that of the rule of 5 (62.9% vs. 37.5%; P < 0.001). If the rule of 5 was required to be repeatable on a consecutive test, specificity improved to 93.4%, but hit rate decreased to 21.0%. At this higher specificity, trend-based analysis still had a significantly greater hit rate than the rule of 5 (47.4% vs. 21.0%, respectively; P < 0.001).

Conclusions: Trend-based analysis was superior to the simple rule of 5 for identifying progression in glaucoma eyes and should be preferred as a method for longitudinal assessment of global SD-OCT RNFL change over time.