Online-Only Supplemental Materials
• Supplemental Methods
• Supplemental Table S1: Age distribution of volunteers in the first (S1a) and second (S1b) examinations (N = 421)
• Supplemental Table S2: The clinical characteristics of each grade (N, N2, N3, GS).
• Supplemental Figure 1: The correlation between the 10-year change in the vertical cup-to-disc ratio and the intraocular pressure at the first examination.
• Supplemental Figure 2:The correlation between the 10-year change in the vertical cup-to-disc ratio and the age at the first examination
• Supplemental Figure 3. The correlation between the 10-year change in the vertical cup-to-disc ratio and the age at the first examination by gender,
Supplemental Methods Subject enrollment
At the beginning of the study, we approached people close to us who had never been diagnosed with glaucoma and asked them to participate in the study. Over time, we began to ask actively participating volunteers to introduce new friends who were interested in eye health and who had never been diagnosed with glaucoma to increase the number of volunteers. No rewards were offered to the volunteers.
To estimate the glaucoma transition rate (GTR) in the second examination 10 years after the first examination, 421 volunteers were enrolled in the second examination. First, 842 volunteers were nominated for the second examination from volunteers who met both of the following two criteria: diagnosis of non-glaucoma in the first examination and time passage exactly 10 ± 0.5 years from the first examination between April 2016 and July 2019. Among these nominated 842 volunteers, 421 volunteers who expressed active consent to join our study were enrolled in the second round of examinations. The reduction of 842 nominees to 421 enrolled volunteers is due to refusals, failure to communicate, relocation to other addresses too far to participate, and so on, after the passing of a 10-year period.
Measurement of clinical parameters
Fundus photography: Fundus photography was conducted using TRC-NW200 (45 degrees; Topcon, Tokyo, Japan).
Slit lamp: One glaucoma specialist (YI) performed anterior and posterior slit lamp examinations using 90D lenses in all volunteers.
Intraocular pressure and gonio lens examination: Intraocular pressure (IOP) was measured with a noncontact tonometer (RKT-7700, Nidek, Gamagori, Japan). Until May 2008, one glaucoma specialist (YI) measured IOP using a Goldmann applanation tonometer (GAT:Haag-Streit AG, Bern, Switzerland, Rodenstock Instruments, Munich, Germany) and a gonio lens examination in volunteers who showed an IOP ≥20 mmHg using a noncontact tonometer, a Van Heric less than 3/4 in the slit lamp examination, suspected glaucoma, or scotoma in the visual field using frequency-doubling technology (FDT). After June 2008, the YI measured IOP in all volunteers using an applanation tonometer and a gonio lens examination. Correction IOP was calculated by the following formula1: correction IOP = measured IOP -0.012 (central cornea thickness
[μm] -520).
Spherical equivalent/spherical keratometric mean: The spherical equivalent and spherical keratometric mean were measured using a noncontact tonometer (RKT-7700, Nidek, Gamagori, Japan).
Visual field test: The visual field was evaluated by FDT perimetry (24-2 central screening mode) (Matrix; Carl Zeiss Meditec, Jena, Germany). If the subject had more than one scotoma in the FDT perimetry, we performed an additional FDT test. If the FDT test showed an abnormality in at least one eye, we performed Humphrey automated perimetry using the 30-2 SITA Fast program (Carl Zeiss Meditec, Jena, Germany).
Disc area/cup area/rim area/vertical cup-to-disc ratio: Disc area/cup area/rim area/vertical cup-to-disc ratio were measured using a confocal scanning laser
ophthalmoscope (HRT-II; Heidelberg Engineering GmbH, Heidelberg, Germany). For the analysis, we selected subjects who had spherical refraction of more than -12D and less than +12D, and SD of less than 50. A contour line of the optic disc margin was drawn around the inner margin of the peripapillary scleral ring by an experienced glaucoma specialist (YI). Magnification errors were corrected using the subjects’
spherical equivalent and spherical keratometric mean.
Anterior chamber (AC) depth (ACD)/volume (ACV)/angle (ACA):
ACD/ACV/central cornea thickness (CCT) was measured using a 3D rotating
Scheimpflug camera, Pentacam® (OCULUS Optikgerate GmbH, Wetzlar, Germany).
For the analysis, we selected the subjects’ data on good Q scores for CCT, including both phakia eyes for ACD, ACV, and ACA.
Axial length: Axial length was measured using IOL Master 700 (Carl Zeiss Meditec, Jena, Germany, version 1.70.16.55256).
Optical coherence tomography (OCT): OCT was taken at the first (Optovue, Inc., Fremont, CA, USA) and second examinations (RS-300, NIDEK). If the visual field was abnormal with myopic changes, we judged whether the visual field abnormality was consistent with the optic nerve. In cases where we were not certain whether the visual field abnormality was myopic or not, we referred to the GCC data to diagnose as glaucoma.
References
1 Suzuki S, Suzuki Y, Iwase A, Araie M. Corneal thickness in an ophthalmologically normal Japanese population. Ophthalmology 2005;112(8):1327-1336. DOI:
10.1016/j.ophtha.2005.03.022
Supplemental Table S1. Age distribution of volunteers in the first and second examinations (N = 421)
a. First examination
b. Second examination
This table shows the age distribution of 421 volunteers who received the second examination 10 years after the first examination. In the first examination, all subjects were diagnosed with non-glaucoma. There was no significant difference in the age of the N1, N2, N3, and GS groups (chi-square test: p > 0.05).
Supplemental Table S1a shows the category status in the first examination, and Supplemental S1b shows it in the second examination. N1, N2, N3: Three classified normal subjects according to vertical cup-to-disk ratio. GS = glaucoma suspect, GL = glaucoma
Male Female N1 N2 N3 GS GL
Age, yrs; mean(SD) 69.9 (9.9) 68.8 (8.2) 67.4 (8.6) 69.1 (8.8) 69.7 (8.9) 66.5 (8.4) 73.0 (7.2) Age groups, yrs; n(%)
50–59 25 (36.2) 44 (63.8) 8 (11.6) 33 (47.8) 22 (31.9) 5 (7.2) 1 (1.4)
60–69 37 (25.9) 106 (74.1) 13 (9.1) 75 (52.4) 44 (30.8) 10 (7.0) 1 (0.7)
70–79 46 (28.6) 115 (71.4) 13 (8.1) 72 (44.7) 63 (39.1) 5 (3.1) 8 (5.0)
80 and older 23 (47.9) 25 (52.1) 2 (4.2) 26 (54.2) 17 (35.4) 1 (2.1) 2 (4.2)
All subjects 131 (31.1) 290 (68.9) 36 (8.6) 206 (48.9) 146 (34.7) 21 (5.0) 12 (2.9)
Male Female N1 N2 N3 GS
Age, yrs; mean(SD) 59.5 (10.0) 58.5 (8.4) 58.4 (8.2) 58.9 (9.4) 59.0 (8.9) 58.5 (7.9) Age groups, yrs; n(%)
40–49 26 (37.1) 44 (62.9) 12 (17.1) 41 (58.6) 14 (20.0) 3 (4.3)
50–59 37 (25.0) 111 (75.0) 29 (19.6) 73 (49.3) 37 (25.0) 9 (6.1)
60–69 47 (29.6) 112 (70.4) 29 (18.2) 83 (52.2) 37 (23.3) 10 (6.3)
70–79 20 (46.5) 23 (53.5) 6 (14.0) 25 (58.1) 12 (27.9) 0 (0.0)
80 and older 1 (100.0) 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0)
All subjects 131 (31.1) 290 (68.9) 76 (18.1) 223 (53.0) 100 (23.8) 22 (5.2)
Supplemental Table S2. Clinical characteristics of each grade (right eye).
Data are shown as mean (standard deviation), except familial history, and familial history; N (%).
P value was analyzed by the AVOVA test.
DA: disc area; CA: cup area; RA: rim area; VCDR: vertical cup-to-disc ratio; CCT:
central cornea thickness; NCT: noncontact; IOP: intraocular pressure; ACD: anterior chamber depth; ACV: anterior chamber volume; ACA: anterior chamber angle; AL:
axial length
Parameter N1 N2 N3 GS P value
DA (mm2) 1.55 (0.33) 1.93 (0.36) 2.11 (0.49) 2.34 (0.49) <0.001
CA (mm2) 0.19 (0.18) 0.47 (0.27) 0.74 (0.33) 0.92 (0.33) <0.001
RA (mm2) 1.36 (0.25) 1.46 (0.28) 1.38 (0.34) 1.43 (0.34) 0.006
VCDR 0.3 (0.15) 0.47 (0.12) 0.57 (0.12) 0.60 (0.12) <0.001
CCT (μm) 546.08 (29.42) 541.53 (31.74) 540.18 (34.67) 550.26 (34.67) 0.180
NCT IOP (mmHg) 13.54 (2.85) 13.75 (2.53) 14.19 (3.13) 14.02 (3.13) 0.174
NCT IOP (correction with CCT) (mmHg) 13.15 (2.54) 13.57 (2.43) 13.94 (3.09) 13.62 (3.09) 0.160
Applanation IOP (mmHg) 12.56 (2.05) 12.66 (2.45) 12.77 (2.17) 13.08 (2.17) 0.844
Applanation IOP (correction with CCT) (mmHg) 11.87 (1.99) 12.17 (2.18) 12.39 (2.08) 12.58 (2.08) 0.725
ACD (mm) 2.75 (0.44) 2.72 (0.46) 2.73 (0.39) 2.71 (0.39) 0.911
ACV (mm3) 145.3 (51.15) 140.35 (38.14) 146.06 (37.23) 149.07 (37.23) 0.321
ACA (°） 33.33 (5.93) 33.54 (6.34) 33.31 (6.07) 32.61 (6.07) 0.819
AL(mm) 23.62 (1.37) 23.56 (1.17) 23.96 (1.45) 24.51 (1.45) <0.001
Sperical equivalent (D) -0.52 (2.18) -0.69 (2.58) -1.08 (2.76) -2.07 (2.76) 0.001
Spherical keratometric mean (D) 7.61 (0.27) 7.68 (0.27) 7.74 (0.30) 7.73 (0.3) <0.001 Family history
No 141 (93.4) 377 (90.6) 168 (86.6) 56 (91.8) 0.202
Yes 10 (6.6) 39 (9.4) 26 (13.4) 5 (8.2)
Right eye
Supplemental Figure 1.The correlation between the 10-year change in the vertical cup-to-disc ratio and intraocular pressure at the first examination.
There was no significant correlation between the 10-year change in the vertical cup-to- disc ratio and intraocular pressure at the first examination (Pearson’s correlation coefficient, r = -0.08, p = 0.437). The vertical cup-to-disc ratio were measured using a confocal scanning laser ophthalmoscope (HRT-II; Heidelberg Engineering GmbH, Heidelberg, Germany) as described in Supplemental Methods. N = 238.
VCDR: vertical cup-to-disc ratio; IOP: intraocular pressure
Supplemental Figure 2. The correlation between the 10-year change in the vertical cup-to-disc ratio and age at the first examination.
There was no significant correlation between the 10-year change in the vertical cup-to- disc ratio and the age of the subject at the first examination (Pearson’s correlation coefficient, r = -0.05, p = 0.419). The vertical cup-to-disc ratio were measured using a confocal scanning laser ophthalmoscope (HRT-II; Heidelberg Engineering GmbH, Heidelberg, Germany) as described in Supplemental Methods. N = 253.
VCDR: vertical cup-to-disc ratio.
Supplemental Figure 3. The correlation between the 10-year change in the vertical cup-to-disc ratio and age at the first examination by gender.
There was no significant correlation between the 10-year change in the vertical cup-to- disc ratio and the both age at the first examination (male: Pearson’s correlation
coefficient, r = -0.09, p = 0.449, female: r = -0.03, p = 0.718). The vertical cup-to-disc ratio were measured using a confocal scanning laser ophthalmoscope (HRT-II;
Heidelberg Engineering GmbH, Heidelberg, Germany) as described in Supplemental Methods. Male: n = 77; Female: n = 176.
VCDR: vertical cup-to-disc ratio