Diagnostic Performance of the ISNT Rule for Glaucoma Based on the Heidelberg Retinal Tomograph (vol 2, 2, 2013)

Purpose: We determined the accuracy of the inferior > superior > nasal > temporal (ISNT) neuroretinal rim area rule and its variants in adult Asian populations, and evaluated whether disc area impacts its performance characteristics. Methods: Participants in the Singapore Malay Eye Study (SiMES) and Singapore Indian Eye Study (SINDI) underwent standardized ocular examinations, including optic disc imaging with the Heidelberg retinal tomograph (HRT). Glaucoma was defined using the ISGEO criteria. HRT rim areas in the superior, inferior, nasal, and temporal quadrants were quantified. We determined sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of violating the ISNT rule and 4 variants (I > S > T, I > S, I > T, and combined I > T and S > T). The influence of disc area was analyzed with multivariate marginal logistic regression. Results: There were 6112 participants (mean age: 57.6 +/- 10.3 years). Glaucoma was present in 194 individuals (3.2%). Among 11,840 eyes, 232 (93.2%) of 249 glaucomatous eyes and 9768 (84.3%) of 11,591 nonglaucomatous eyes, violated the ISNT rule. The ISNT rule had highest sensitivity (93.5%), but lowest specificity (15.7%); I > T had highest specificity (98.2%), but low sensitivity (7.4%). For all variants, PPVs were low (2.1%-8.4%) and NPVs were high (97.9-99.1%). Larger disc area was associated with reduced specificity for the ISNT rule (P < 0.001), and reduced sensitivity (P = 0.01) and increased specificity for I > S > T (P < 0.05). PPV increased (P < 0.05) and NPV decreased (P < 0.001) with increasing disc area. Conclusions: The ISNT rule based on HRT has high sensitivity, and the I > T, S > T, and combined I > T and S > T variants have high specificity. Disc area influences sensitivity, specificity, PPV, and NPV of the ISNT rule and its variants.