Informed consent was obtained from all patients, and the study was approved by the Institutional Review Boards of the National University Hospital of Singapore and the Singapore Eye Research Institute. The research was performed in accordance with the tenets of the Declaration of Helsinki. The subject population for this study was a subset selected from a larger study of 203 subjects aged 40 years or older that included patients with suspected glaucoma and patients with glaucoma, ocular hypertension, or primary angle closure. Subjects were recruited from the glaucoma service at the National University Hospital, Singapore and the majority (71%) had a clinical diagnosis of treated or untreated primary angle closure. All subjects underwent gonioscopy and AS-OCT imaging.
Gonioscopy was performed under dim illumination with a Goldmann two-mirror lens. An angle quadrant was classified as closed on gonioscopy if the iris was in contact with the posterior trabecular meshwork. An individual was classified with angle-closure if one or more of the temporal, inferior, and nasal quadrants of the angle were closed in either eye.
Imaging of the nasal, temporal, and inferior AC angles was performed with an AS-OCT prototype (Carl Zeiss Meditec, Inc., Dublin, CA) under standardized dark and light conditions.
Figure 1is an example of an AS-OCT image of the nasal and temporal angles obtained with this instrument. The prototype used a 1.3-μm-wavelength light with a scan speed of 2000 A-scans per second and a full width-half maximum axial resolution of 17 μm in tissue. The scan depth was 8 mm, and the scan length was 16 mm. An accommodative internal fixation target was used, and the spherical equivalent of the subject’s distance spectacle correction was dialed into the instrument optics so that imaging was performed in a nonaccommodated state. The superior quadrant could not be imaged because the bulky casing and short working distance of the prototype instrument used in this study prevented the operator from lifting the subject’s upper eyelid with a cotton tip applicator or other devices. A commercially available OCT (Visante; Carl Zeiss Meditec) has a greater working distance and may allow the operator to use a device to lift the upper eyelid and image the superior quadrant. The other design difference between the prototype and the OCT was a joystick control for patient positioning in the former versus a motorized chin-rest in the latter.
For short-term reproducibility analysis, a single observer acquired two sets of images (sessions 1 and 2, respectively), followed by a third set of images (session 3) acquired by a second observer. The subject was repositioned for each session. The interval between each of the three sessions was 10 minutes. The first set of images acquired by the first observer (session 1) was used for analysis of interobserver reproducibility. For long-term reproducibility analysis, a single observer acquired two sets of images (sessions A and B, respectively) with the mean time between sessions being 10.5 weeks (range, 1 day–73 weeks; median, 3 weeks). Each set of images consisted of one image each of the nasal, inferior, and temporal quadrants obtained with the eye in primary gaze. If the lower lid prevented visualization of the inferior angle, the patient was instructed to hold the lid down against the infraorbital rim.
All images were measured offline by an independent, masked third observer, who used custom software (MathWorks, Natick, MA)
9 to determine the AC depth (ACD), angle opening distance at 500 μm (AOD
500), angle recess area at 500 μm and 750 μm (ARA
500 and ARA
750), and trabecular–iris space area at 500 and 750 μm (TISA
500 and TISA
750, respectively;
Fig. 2 ). Images of the right eye were used; left eye data were included only if data from the right eye were not available. The software was semiautomated. The operator first marked the anterior and posterior corneal surfaces and the anterior iris surface with the mouse so that the image could be corrected for the effects of refraction at the cornea and the fan-shaped scan geometry of the device. The operator then marked the scleral spur, after which the program calculated the aforementioned quantitative parameters. All images of a particular subject were measured at one sitting. The AOD
500 was defined as the linear distance between the trabecular meshwork and the iris at 500 μm anterior to the scleral spur.
10 The ARA was defined as the triangular area formed by the AOD
500 or AOD
750 (the base), the angle recess (the apex), the iris surface, and the inner corneoscleral wall (sides of triangle).
11 The TISA was defined as the trapezoidal area with the following boundaries: anteriorly, the AOD
500 or AOD
750; posteriorly, a line drawn from the scleral spur perpendicular to the plane of the inner scleral wall to the opposing iris; superiorly, the inner corneoscleral wall and inferiorly, the iris surface.
5
The correlation between gonioscopy and angle parameters measured by AS-OCT was calculated using the Pearson correlation coefficient. Analysis of variance was used to calculate the intraclass correlation coefficient (ICC) as a measure of intraobserver and interobserver reproducibility. An ICC of <0.4 indicated poor reproducibility, between 0.4–0.75 indicated fair to good reproducibility, and >0.75 indicated excellent reproducibility. The mean of measurements from paired data sets (sessions 1 and 2 for intraobserver short-term reproducibility, sessions 1 and 3 for interobserver short-term reproducibility, and sessions A and B for intraobserver long-term reproducibility), the difference between measurements from paired data sets and the 95% confidence interval for this difference were also calculated.