ISNT Rule in Normal Population

Glaucoma is a disease of the optic nerve, which results in structural optic nerve head (ONH) damage and functional visual field (VF) loss. It has increased as a cause of global blindness from 4.4% in 1990 to 6.3% in 2010. Its global prevalence is also increasing from 3.54% or 64.3 million people in 2013 to a projected 111.8 million people by 2040. Detection of structural ONH damage is critical for early diagnosis, because ONH changes usually precede VF loss. Two cornerstone elements of the ONH and peripapillary examination are stereo disc photography and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements. By analyzing the neuroretinal rim in disc photos of normal subjects, Jonas et al found that the rim width typically exhibited a specific pattern of the inferior (I) rim being the widest, followed by the superior (S) rim, then the nasal (N) rim, and then the temporal (T) rim being the thinnest. This specific neuroretinal rim pattern was later coined by Elliot Werner as the "ISNT rule." Because neuroretinal rim loss is a hallmark feature of glaucoma, patients who deviate from the ISNT rule may need to be watched more closely for glaucoma. The RNFL, on the other hand, has also been shown in histological studies in normal, non-glaucomatous eyes to exhibit a similar pattern of the inferior quadrant being the thickest, followed by the superior, nasal, then temporal quadrant. Since RNFL thinning, particularly in the superior and inferior quadrants, is also a characteristic structural change in glaucoma, deviation from the ISNT rule for RNFL thickness may also be an early indicator of glaucomatous structural change. Therefore, many investigators have sought to determine whether the ISNT rule, either applied to the neuroretinal rim disc photos or to RNFL thickness measurements, is useful in the diagnosis of glaucoma or not. However, the optic disc photo ISNT rule studies are conflicting, with some finding the ISNT rule and its variants clinically useful, while others have not. In contrast, RNFL ISNT rule studies based on OCT findings are in uniform agreement, stating that the ISNT rule and its variants were not helpful in the diagnosis of glaucoma. Some have hypothesized that the ISNT rule is not easily generalizable to the individual, because the initial studies were derived from mean values. Therefore, some of the limitations of the ISNT rule may stem from the fact that it is unclear what percentage of individual normal eyes follow the ISNT rule. Other limitations may arise from the fact that perhaps other rules may be more common in the normal population.