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

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.

Prospective cohort.

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.

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.

Comparison between hit rates of trend-analysis versus rule of 5 at matched specificity.

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).

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.