Diagnostic Performance of the ISNT Rule for Glaucoma Based on the Heidelberg Retinal Tomograph.

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. TRANSLATIONAL RELEVANCE The high sensitivity of the ISNT rule, and high specificities of its variants, may have potential utility when used in combination with other HRT algorithms for glaucoma assessment.

[1]  R. Hitchings,et al.  The optic disc in glaucoma II: correlation of the appearance of the optic disc with the visual field. , 1977, The British journal of ophthalmology.

[2]  Airaksinen Pj,et al.  Neuroretinal rim area and retinal nerve fiber layer in glaucoma. , 1985 .

[3]  J. Jonas,et al.  Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. , 1988, Investigative ophthalmology & visual science.

[4]  K Rohrschneider,et al.  Reproducibility of the optic nerve head topography with a new laser tomographic scanning device. , 1994, Ophthalmology.

[5]  S. Drance,et al.  The effect of optic disc size on diagnostic precision with the Heidelberg retina tomograph. , 1997, Ophthalmology (Rochester, Minn.).

[6]  W Leisenring,et al.  A marginal regression modelling framework for evaluating medical diagnostic tests. , 1997, Statistics in medicine.

[7]  Jost B Jonas,et al.  Neuroretinal rim width ratios in morphological glaucoma diagnosis , 1998, The British journal of ophthalmology.

[8]  P A Sample,et al.  Detection of early glaucomatous structural damage with confocal scanning laser tomography. , 1998, Journal of glaucoma.

[9]  C. Rutter,et al.  Bootstrap estimation of diagnostic accuracy with patient-clustered data. , 2000, Academic radiology.

[10]  L. Zangwill,et al.  Discriminating between normal and glaucomatous eyes using the Heidelberg Retina Tomograph, GDx Nerve Fiber Analyzer, and Optical Coherence Tomograph. , 2001, Archives of ophthalmology.

[11]  P. Foster,et al.  The definition and classification of glaucoma in prevalence surveys , 2002, The British journal of ophthalmology.

[12]  A. Coleman,et al.  Comparison of optic nerve imaging methods to distinguish normal eyes from those with glaucoma. , 2002, Investigative ophthalmology & visual science.

[13]  Jost B Jonas,et al.  GEE approaches to marginal regression models for medical diagnostic tests , 2004, Statistics in medicine.

[14]  S. Vernon,et al.  Specificity of the Heidelberg Retina Tomograph's diagnostic algorithms in a normal elderly population: the Bridlington Eye Assessment Project. , 2006, Ophthalmology.

[15]  Robert Ritch,et al.  The ISNT rule and differentiation of normal from glaucomatous eyes. , 2006, Archives of ophthalmology.

[16]  F. Medeiros,et al.  Influence of disease severity and optic disc size on the diagnostic performance of imaging instruments in glaucoma. , 2006, Investigative ophthalmology & visual science.

[17]  Augusto Azuara-Blanco,et al.  The quality of reporting of diagnostic accuracy studies in glaucoma using the Heidelberg retina tomograph. , 2006, Investigative ophthalmology & visual science.

[18]  T. Wong,et al.  Rationale and Methodology for a Population-Based Study of Eye Diseases in Malay People: The Singapore Malay Eye Study (SiMES) , 2007, Ophthalmic epidemiology.

[19]  A. Ferreras,et al.  Diagnostic ability of Heidelberg Retina Tomograph 3 classifications: glaucoma probability score versus Moorfields regression analysis. , 2007, Ophthalmology.

[20]  Robert N Weinreb,et al.  The effect of disc size and severity of disease on the diagnostic accuracy of the Heidelberg Retina Tomograph Glaucoma Probability Score. , 2007, Investigative ophthalmology & visual science.

[21]  Ronnie George,et al.  Neural rim characteristics of healthy South Indians: the Chennai Glaucoma Study. , 2008, Investigative ophthalmology & visual science.

[22]  L. Rossetti,et al.  Exploring the Heidelberg Retinal Tomograph 3 diagnostic accuracy across disc sizes and glaucoma stages: a multicenter study. , 2008, Ophthalmology.

[23]  T Dada,et al.  Is the ISNT rule violated in early primary open-angle glaucoma—a scanning laser tomography study , 2008, Eye.

[24]  Tin Aung,et al.  The prevalence and types of glaucoma in malay people: the Singapore Malay eye study. , 2008, Investigative ophthalmology & visual science.

[25]  Joel S Schuman,et al.  Diagnostic tools for glaucoma detection and management. , 2008, Survey of ophthalmology.

[26]  P. Mitchell,et al.  Methodology of the Singapore Indian Chinese Cohort (SICC) Eye Study: Quantifying ethnic variations in the epidemiology of eye diseases in Asians , 2009, Ophthalmic epidemiology.

[27]  M. Michelessi,et al.  Sector-based analysis with the Heidelberg Retinal Tomograph 3 across disc sizes and glaucoma stages: a multicenter study. , 2009, Ophthalmology.

[28]  Ecosse Lamoureux,et al.  Diagnostic ability of Heidelberg Retina Tomography in detecting glaucoma in a population setting: the Singapore Malay Eye Study. , 2010, Ophthalmology.

[29]  Katherine L. Pogrebniak,et al.  Violation of the ISNT rule in Nonglaucomatous pediatric optic disc cupping. , 2010, Investigative ophthalmology & visual science.

[30]  Rachel V North,et al.  The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule for diagnosing glaucomatous optic disc damage. , 2012, Ophthalmology.