**Purpose.**:
To evaluate the reproducibility of anterior chamber angle measurements obtained by swept-source optical coherence tomography (OCT) and to identify factors associated with its measurement variability.

**Methods.**:
One eye from each of 30 healthy subjects was randomly selected for anterior segment OCT imaging (Casia SS-1000 OCT; Tomey, Nagoya, Japan) in three separate visits within a week. The angle opening distance (AOD), the trabecular iris space area (TISA), and the trabecular-iris angle (TIA) at the superior (90°), nasal (0°), inferior (270°), and temporal (180°) angles were measured. The intraobserver and interobserver reproducibility coefficient (RC) and intraclass correlation coefficient (ICC) were calculated. Generalized linear latent and mixed modeling was used to examine the association between the variance of angle measurements and each of the following: angle width, pupil diameter, pupil diameter variance, iris thickness, iris thickness variance, axial length, anterior chamber depth, scan location, scleral spur visibility, and age.

**Results.**:
The intervisit, intraobserver RCs ranged between 0.140 mm and 0.252 mm for AOD, 0.050 mm^{2} and 0.090 mm^{2} for TISA, and 7.7° and 9.5° for TIA, and the interobserver RCs were between 0.103 mm and 0.187 mm, 0.049 mm^{2} and 0.101 mm^{2}, and 8.5° and 13.7°, respectively. The ICCs were all ≥0.83. Increased iris thickness, increased iris thickness variance, angle measured at the superior and inferior quadrants, increased angle width, and long axial length were associated with increased variance of angle measurements.

**Conclusions.**:
Although the swept-source OCT had high reproducibility for angle measurement, differences in iris thickness, angle width, measurement location, and axial length may influence its variability.

^{ 1 –7 }The Visante optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA) and the slit-lamp OCT (SL-OCT; Heidelberg Engineering GmbH, Dossenheim, Germany) are noncontact imaging devices that have been shown to be repeatable and reproducible for measurement of the angle.

^{ 8 –12 }Both instruments are time-domain OCT with a respective scan speed of 2000 A-scans and 200 A-scans per second. With a frame size of 256 A-scans and 215 A-scans, respectively, it takes 0.125 seconds for Visante OCT and 1.075 seconds for SL-OCT to capture a single cross-sectional image. The relatively slow scan rate limits the sampling density for both instruments and may increase the propensity for motion artifact for SL-OCT.

^{ 13,14 }The Casia SS-1000 OCT (Tomey, Nagoya, Japan) is a commercially available swept-source OCT with a swept-source laser wavelength of 1310 nm.

^{ 15 }A scleral spur visibility score (SSVS) of 2 and 1 denoted a clearly and a moderately visible scleral spur, respectively. A SSVS of 0 indicated the scleral spur was not visible. Subjects were included in the analysis only when all angles from all three images had a SSVS of at least 1. Three subjects were excluded because the scleral spur was not detectable in at least one quadrant in any of the three scans taken per eye. AOD was calculated as the perpendicular distance measured from the trabecular meshwork at 500 μm anterior to the scleral spur to the anterior iris surface.

^{ 16 }TISA was an area bounded anteriorly by the AOD, posteriorly by a line drawn from the scleral spur perpendicular to the plane of the inner scleral wall to the opposing iris, superiorly by the inner corneoscleral wall, and inferiorly by the iris surface.

^{ 17 }TIA was defined as an angle measured with the apex in the iris recess and the arms of the angle passing through a point on the trabecular meshwork 500 μm from the scleral spur and the point on the iris perpendicularly opposite.

^{ 16 }Superior (90°), nasal (0°), inferior (270°), and temporal (180°) angles were measured. Pupil diameter was measured as iris tip-to-tip distance. Anterior chamber depth (ACD) was defined as the perpendicular distance from the corneal endothelium at the corneal apex to the anterior lens surface. Iris thickness was defined as the distance between the anterior and posterior iris surfaces at 500 μm from the scleral spur. Pupil diameter, iris thickness, and ACD were measured from the OCT image. The horizontal meridian of each of the three image series of each eye was selected for measurement of pupil diameter and ACD. The average of three measurements was analyzed. Axial length was measured with an optical biometer (IOLMaster, version 3.0.1; Carl Zeiss Meditec, Dublin, CA). Iris and corneal boundaries were checked for all angle, iris, and ACD measurements. There were no segmentation errors in the analyzed images.

^{ 18 }The interpretation is that 95% of the difference between measurements obtained from two separate occasions would be less than the RC. ICC was interpreted as follows: <0.75 represents poor to moderate reliability, 0.75 to 0.90 represents good reliability, and >0.90 represents excellent reliability for clinical measures.

^{ 19 }By setting the 95% confidence interval as 20% on either side of the estimate of within-subject standard deviation Sw [

*n*= 1.96

^{2}/(2 × 0.2

^{2}× (

*m*-1)],

^{ 20 }where

*n*is the number of subjects and

*m*is the number of observations, it was estimated that a minimum of 25 subjects was required. Angle measurements at different quadrants were compared with Wilcoxon signed-rank tests at the 5% level of significance with Bonferroni adjustment. Generalized linear latent and mixed modeling was used to evaluate the effects of mean angle width, mean pupil diameter, variance of pupil diameter, iris thickness, variance of iris thickness, axial length, anterior chamber depth, SSVS, age, and scan location on the variances of AOD, TISA, and TIA. In brief, the angle variance (

*varANGLE*) was regressed on the mean angle (

*ANGLE*), mean pupil diameter (

*PD*), variance of pupil diameter (

*varPD*), mean iris thickness (

*IT*), variance of iris thickness (

*varIT*), axial length (

*AL*), anterior chamber depth (ACD), SSVS, age (

*AGE*), and the scan location (

*TEMPORAL, SUPERIOR*, and

*INFERIOR*), with random subject effect as the random intercept using uniform link function: where β

_{0}− β

_{9}represent the fixed effects associated with the intercept, mean value of the angle measurement, pupil diameter, variance of pupil diameter, iris thickness, variance of iris thickness, axial length, anterior chamber depth, subject age, and scleral spur visibility score, respectively; β

_{10}− β

_{12}represents the fixed effects associated with the scan location (Three variables—TEMPORAL, SUPERIOR, INFERIOR—were used to denote the four scan locations. For example, temporal measurement was coded as

*TEMPORAL*= 1,

*SUPERIOR*= 0,

*INFERIOR*= 0. Nasal measurement was coded as TEMPORAL = 0, SUPERIOR = 0, INFERIOR = 0. The nasal quadrant was set as a reference location for comparison with other quadrants.); η

_{0}represents the random subject effects associated with the intercept; and ε represents the residual. Insignificant factors were removed by backward selection after performing likelihood-ratio test at the 5% significance level. Comparisons of estimates among the quadrants were performed with the Wald test.

*P*< 0.05 was considered statistically significant.

^{2}to 0.497 mm

^{2}, and 0.0° to 61.9°, respectively. Angle measurements of the superior quadrant were significantly smaller than those measured in the other quadrants (

*P*< 0.001). The iris was thicker in the superior and inferior quadrants, whereas the SSVS was greater in the nasal and temporal quadrants (Table 1).

P of Pairwise Comparison* | T | ||||
---|---|---|---|---|---|

Mean ± SD | S | N | I | ||

AOD 500, mm | |||||

S | 0.319 ± 0.212 | — | 0.000† | 0.000† | 0.000† |

N | 0.454 ± 0.230 | 0.000† | — | 0.043 | 0.003† |

I | 0.491 ± 0.277 | 0.000† | 0.043 | — | 0.319 |

T | 0.507 ± 0.272 | 0.000† | 0.003† | 0.319 | — |

TISA 500, mm^{2} | |||||

S | 0.100 ± 0.088 | — | 0.000† | 0.000† | 0.000† |

N | 0.155 ± 0.084 | 0.000† | — | 0.734 | 0.280 |

I | 0.153 ± 0.098 | 0.000† | 0.734 | — | 0.382 |

T | 0.160 ± 0.095 | 0.000† | 0.280 | 0.382 | — |

TIA, deg | |||||

S | 25.3 ± 11.7 | — | 0.000† | 0.001† | 0.000† |

N | 32.9 ± 11.1 | 0.000† | — | 0.104 | 0.079 |

I | 31.1 ± 10.9 | 0.001† | 0.104 | — | 0.003† |

T | 34.8 ± 11.0 | 0.000† | 0.079 | 0.003† | — |

IT 500, mm | |||||

S | 0.354 ± 0.055 | — | 0.086 | 0.047 | 0.002† |

N | 0.335 ± 0.051 | 0.086 | — | 0.001† | 0.280 |

I | 0.371 ± 0.075 | 0.047 | 0.001† | — | 0.000† |

T | 0.323 ± 0.060 | 0.002† | 0.280 | 0.000† | — |

SSVS | |||||

S | 1.51 ± 0.45 | — | 0.000† | 0.959 | 0.001† |

N | 1.96 ± 0.19 | 0.000† | — | 0.000† | 1.000 |

I | 1.52 ± 0.45 | 0.959 | 0.000† | — | 0.000† |

T | 1.94 ± 0.22 | 0.001† | 1.000 | 0.000† | — |

^{2}and 0.090 mm

^{2}for TISA, and 7.7° and 9.5° for TIA. Interobserver RCs ranged between 0.103 mm and 0.187 mm, 0.049 mm

^{2}and 0.101 mm

^{2}, and 8.5° and 13.7°, respectively (Table 2). In general, the RC was greatest (i.e., the highest measurement variability) at the inferior quadrant. The ICC for all parameters was ≥0.83.

RC (95% CI) | ICC (95% CI) | |||
---|---|---|---|---|

Intraobserver | Interobserver | Intraobserver | Interobserver | |

AOD 500, mm | ||||

S | 0.140 (0.115–0.165) | 0.158 (0.118–0.198) | 0.94 (0.90–0.97) | 0.93 (0.85–0.97) |

N | 0.141 (0.116–0.166) | 0.116 (0.087–0.145) | 0.95 (0.91–0.98) | 0.97 (0.94–0.99) |

I | 0.252 (0.207–0.297) | 0.187 (0.140–0.235) | 0.90 (0.83–0.95) | 0.94 (0.88–0.97) |

T | 0.224 (0.184–0.265) | 0.103 (0.077–0.129) | 0.91 (0.85–0.96) | 0.98 (0.96–0.99) |

TISA 500, mm^{2} | ||||

S | 0.074 (0.061–0.087) | 0.083 (0.062–0.103) | 0.91 (0.84–0.95) | 0.90 (0.81–0.95) |

N | 0.050 (0.041–0.059) | 0.049 (0.037–0.062) | 0.95 (0.92–0.98) | 0.96 (0.91–0.98) |

I | 0.090 (0.074–0.106) | 0.101 (0.075–0.126) | 0.90 (0.83–0.95) | 0.86 (0.74–0.93) |

T | 0.086 (0.071–0.101) | 0.051 (0.038–0.064) | 0.90 (0.83–0.95) | 0.96 (0.93–0.98) |

TIA 500, deg | ||||

S | 7.7 (6.4–9.1) | 13.3 (9.9–16.6) | 0.94 (0.90–0.97) | 0.88 (0.77–0.94) |

N | 8.9 (7.3–10.5) | 13.7 (10.2–17.2) | 0.92 (0.86–0.96) | 0.83 (0.68–0.92) |

I | 9.5 (7.8–11.2) | 13.4 (10.0–16.8) | 0.91 (0.83–0.95) | 0.87 (0.74–0.94) |

T | 8.2 (6.8–9.8) | 8.5 (6.4–10.7) | 0.93 (0.87–0.96) | 0.94 (0.87–0.97) |

*P*≤ 0.009) were associated with increased variability of TISA. Greater mean angle width was associated with increased variability of AOD and TISA (

*P*≤ 0.001). TIA variance, in contrast, was not related to the mean angle width or the location of measurement. The only significant factor associated with the variance of TIA was the axial length (

*P*< 0.001), which was also significantly associated with the variance of AOD (

*P*= 0.009). Mean and variance of iris thickness were associated with the variance of AOD (

*P*= 0.027 and

*P*= 0.005, respectively). Age, anterior chamber depth, pupil diameter, variance of pupil diameter, and scleral spur visibility were not related to the variance of angle measurements. Except for iris thickness in the model of AOD (power = 60%) and the temporal quadrant in the model of TISA (power = 14%), the statistical power of all the GLLAM models ranged between 74% and 100%, with an alpha = 5% (Tables 3 4–5).

Coefficient | Estimate | 95% CI | P | Power (%)* | |
---|---|---|---|---|---|

Mean AOD | β_{1} | 1.04 × 10^{−2} | 0.51 × 10^{−2} to 1.56 × 10^{−2} | 0.000 | 97 |

Mean IT | β_{4} | 9.77 × 10^{−3} | 1.13 × 10^{−3} to 18.41 × 10^{−3} | 0.027 | 60 |

IT variance | β_{5} | 9.24 × 10^{−1} | 2.73 × 10^{−1} to 15.76 × 10^{−1} | 0.005 | 79 |

Axial length | β_{6} | 6.29 × 10^{−4} | 1.57 × 10^{−4} to 11.02 × 10^{−4} | 0.009 | 74 |

Intercept | β_{0} | −1.98 × 10^{−2} | −3.04 × 10^{−2} to −0.91 × 10^{−2} | 0.000 | — |

Coefficient | Estimate | 95% CI | P | Power (%)* | |
---|---|---|---|---|---|

Mean TISA | β_{1} | 4.81 × 10^{−3} | 2.74 × 10^{−3} to 6.87 × 10^{−3} | 0.000 | 100 |

Superior† | β_{11} | 4.15 × 10^{−4} | 1.02 × 10^{−4} to 7.29 × 10^{−4} | 0.009 | 74 |

Inferior† | β_{12} | 4.65 × 10^{−4} | 1.32 × 10^{−4} to 7.97 × 10^{−4} | 0.006 | 78 |

Temporal | β_{9} | 1.49 × 10^{−4} | −1.91 × 10^{−4} to 4.89 × 10^{−4} | 0.390 | 14 |

Intercept | β_{0} | −7.7 × 10^{−2} | −143.12 × 10^{−2} to 127.73 × 10^{−2} | 0.911 | — |

Coefficient | Estimate | 95% CI | P | Power (%)* | |
---|---|---|---|---|---|

Axial length | β_{6} | 3.11 | 2.09 to 4.13 | 0.000 | 100 |

Intercept | β_{0} | −6.62 × 10 | −9.07 × 10 to −4.17 × 10 | 0.000 | — |

^{ 11 }the interobserver ICCs of AOD500, AOD750, TISA500, and TISA750 measured by the Visante OCT (Carl Zeiss Meditec) ranged between 0.978 and 0.988. Using the SL-OCT (Heidelberg Engineering), Muller et al.

^{ 12 }reported that the interobserver ICC of the anterior chamber angle was 0.96. Although the ICCs reported by Radhakrishnan et al.

^{ 10 }were generally smaller (0.31–0.73 for the inferior quadrant; 0.56–0.93 for the nasal and temporal quadrants), it is notable that they used a prototype device. The disparities in ICCs would be related to the differences in study populations, study design, instruments, and quadrants of assessment. We showed in a previous study that the intervisit RCs for AOD and TIA measured at the nasal angle in the dark by the Visante OCT were 0.177 mm and 9.4°, respectively (we analyzed only the nasal angle and measured AOD and TIA in this study).

^{ 8 }These values closely resemble those reported in the present study using the Casia SS-1000 OCT (0.141 mm for AOD, 8.9° for TIA at the nasal angle).

^{ 16,17 }They have different units (μm, μm

^{2}, and degree, respectively) and represent different dimensions (length, area, and angle) of the angle. For this reason, it is not surprising to find disparities in the comparisons of angle width (Table 1) and different factors accounting for measurement variability of AOD, TISA, and TIA (Tables 3 4–5). The most consistent observation in the comparison of angle width in different quadrants is that the superior angle was the smallest. This concurs with the earlier studies performed with gonioscopy and ultrasound biomicroscopy showing that the angle is narrower in the superior quadrant.

^{ 21,22 }Although there were also significant differences between the temporal and inferior angles for TIA (

*P*= 0.003) and between the nasal and temporal angles for AOD (

*P*= 0.003), the differences were fairly small (3.7° and 0.053 mm, respectively).

^{ 15,23 }we did not find an association between scleral spur visibility score and any of the angle measurement variances. Without a validated approach to quantify the configuration of the anterior iris surface, it is uncertain whether there are greater variations in iris surface contour in the superior and inferior quadrants and whether such variations, if they exist, contribute to the increased variability of TISA.

^{ 24,25 }The ciliary body is a dynamic structure, and the increase in ciliary body and ciliary muscle thicknesses might impose additional variations in measurement of the angle. Limited by scleral scattering, it is not feasible to visualize the ciliary body in full with the swept-source OCT, and its dimensions were not measured in this study.