Abstract: Retinal nerve fiber layer defect (RNFLD), including localized and diffuse RNFLD, is believed to be a characteristic feature of glaucoma and an important clue for the detection of early glaucoma. However, RNFLD does not always equate to a diagnosis of glaucoma.It can also be induced by systemic or ocular vascular accidents or some other central nervous systemic (CNS) disease, such as hypertension, nonarteritic anterior ischemic optic neuropathy, multiple sclerosis, and so on. For those systemic or CNS diseases, there are strong correlations between RNFLD and visual field loss, which makes it possible to use RNFLD to indicate the severity of the diseases. With recent advances in ocular imaging technology such as OCT, RNFL thickness measurement could potentially be used to evaluate ganglion cell loss in patients with systemic or CNS diseases, and might be used to detect damage and followup of these patients. (Int Rev Ophthalmol, 2014, 38: 93-98)