One hundred fifty-one healthy eyes of 151 Korean adults, 58 early glaucoma eyes of 58 Korean adults, and 62 age-matched additional healthy control eyes of 62 Korean adults were consecutively enrolled in 2013. This study was approved by the Institutional Review Board of CHA Bundang Medical Center and conducted at CHA Bundang Medical Center. The study conformed to the Declaration of Helsinki, and written informed consent was obtained from all subjects. All subjects underwent a full ophthalmologic examination including best-corrected visual acuity (BCVA), Goldmann applanation tonometry by a glaucoma specialist (SR), central corneal thickness (CCT), axial length (AXL), spherical equivalent refractive error (SER), gonioscopy, visual field test, fundus examination after pupil dilation, fundus photography, red-free photography, and spectral-domain optical coherence tomography (SD-OCT). Central corneal thickness was measured using an ultrasonic pachymeter (UP-1000; Nidek, Gamagori, Japan), and AXL was measured using Echoscan (US-4000; Nidek). Fundus photography and red-free photography were performed with a fundus camera (VX-10i; Kowa, Nagoya, Japan).
The inclusion criteria for both the normative group and the validation group were visual acuity of at least 20/30 and age between 18 and 80 years. Subjects with clinical evidence of retinal disease, neuro-ophthalmologic disease, history of refractive or retinal surgery within 3 months, or closed iridocorneal angle and refractive error more than ±8.0 diopters and ±3.0 diopters of cylinder were excluded from both groups. In the normal group, subjects were additionally excluded if they had intraocular pressure (IOP) higher than 21 mm Hg, glaucomatous optic disc, or abnormal visual field test results (described in the section on visual field tests below). Cases of severe myopic degeneration on the retina or physiologic cupping with large optic disc size were also excluded for the sake of accuracy. Subjects were consecutively enrolled in a validation set if they had mean deviation (MD) values higher than −6 decibels (dB; normal or early damage). One eye from each participant was included randomly in the assessment.
The validation group was set to compare the RNFL defect-detecting ability of three different comparative criteria for lower 1% limit. Criterion 1 was from the manufacturer's data; criterion 2 was from the established normative data in 151 healthy Korean eyes; and criterion 3 was from shifting of the data of the established normative values in 151 healthy Korean eyes considering each volunteer's vessel position. For criterion 3, the volunteers' normative data were separated into four subgroups, which were combinations of two superotemporal groups and two inferotemporal groups, according to each volunteer's vessel position, for confirmation of RNFL defects. As the parameter contributing the most to the RNFL peak was the position of the major retinal artery (described in the section on statistical analysis), the superotemporal and inferotemporal subgroups were divided by the median angle degree of the superotemporal and inferotemporal major vessel peaks, respectively. These were designated references 1, 2, 3, and 4 (see more in the sections on RNFL measurement and statistical analysis). All three criteria were assessed based on the standard criterion defined as the “early glaucoma state.” The early glaucoma state was defined as that in which subjects showed glaucomatous optic disc contours plus a corresponding abnormal visual field result, or RNFL defects in red-free photography plus a corresponding abnormal visual field result. Using these parameters, validation subjects were divided into two groups: “healthy control,” which should not be detected by the RNFL defect measurements, or “early glaucoma,” which should be detected by the RNFL defect measurements.