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1From the Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Peoples Republic of China; the 2Hamilton Glaucoma Center, University of California, San Diego, California; 4The New York Eye and Ear Infirmary, New York, New York; the 5Department of Applied Mathematics, Hong Kong Polytechnic University, Hong Kong, Peoples Republic of China; and the 6New York Medical College, Valhalla, New York.
| Abstract |
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METHODS. Thirty-seven normal subjects with open angles on dark-room gonioscopy and 18 subjects with narrow angles were analyzed. The dynamic dark–light changes of the anterior-chamber angle were captured with real-time video recording. The angle opening distance (AOD500) and trabecular iris space area (TISA500) of the nasal angle and the pupil diameter in each of the representative serial images were measured. Linear regression analysis was performed to investigate the association between AOD500/TISA500 and pupil diameter. Demographic and biometry measurements associated with the AOD difference (AOD500(light) – AOD500(dark)) and TISA difference (TISA500(light) – TISA500(dark)) were analyzed with univariate and multivariate regression models.
RESULTS. The AOD500/TISA500 measured in the light in the open-angle and the narrow-angle groups were 694 ± 330 µm/0.24 ± 0.10 mm2 and 265 ± 78 µm/0.10 ± 0.03 mm2, respectively. These values were significantly greater than the AOD500/TISA500 measured in the dark (492 ± 265 µm/0.16 ± 0.08 mm2 and 119 ± 82 µm/0.05 ± 0.04 mm2, respectively, all with P < 0.001). The ranges of the AOD/TISA difference were 13 to 817µm/0.011 to 0.154 mm2, with an average of 180 µm/0.073 mm2. Multivariate regression analysis identified a positive correlation between anterior chamber depth and the AOD/TISA difference. Fifty eyes showed significant correlations between AOD/TISA and pupil diameter, whereas one eye showed no association. Four eyes in the narrow angle group developed appositional angle closure in the dark.
CONCLUSIONS. The dynamic dark–light changes of the anterior chamber angle can be imaged and analyzed with anterior segment OCT. Although the angle width generally decreased linearly with increasing pupil diameter, the differences of the angle width measured in the dark and in the light varied substantially among individuals.
The Visante anterior segment optical coherence tomograph (Carl Zeiss Meditec, Inc. Dublin, CA) was recently introduced to provide noncontact and noninvasive optical imaging of the anterior segment. With this technology, detailed spatial relationships of the structures forming the anterior chamber angle can be visualized and objective angle measurements performed. In addition, the use of the infrared laser and the noncontact technique during examination permits capture of angle morphology in the dark. Anterior segment OCT thus has the potential to provide valuable quantitative and spatial information regarding dynamic changes of the angle configuration not provided by standard gonioscopy. In this study, we investigated and measured the dark–light dynamic changes of the anterior chamber angle with real-time video capture using the anterior segment OCT.
| Materials and Methods |
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Visante Anterior Segment Optical Coherence Tomography Imaging
Each selected eye was imaged with anterior segment optical coherence tomography (The Zeiss Visante OCT Model 1000; Carl Zeiss Meditec, Dublin, CA). The Visante OCT is a noncontact, high-resolution tomographic and biomicroscopic device designed for anterior segment imaging and measurement. The imaging principle is based on low-coherence interferometry, with a 1310-nm superluminescent light-emitting diode (SLD) as the light source. Analogous to an ultrasound B-scan, the Visante OCT acquires multiple A-scans and aligns them to construct two-dimensional images. The scanning of the anterior chamber angle is a noncontact procedure during which the subject fixates on an internal fixation target (wavelength of visual aiming beam is 845 nm). The Visante OCT allows real-time imaging of the anterior chamber with scan speed of 2000 A-scans per second. The scan acquisition time is 0.125 second per line for the anterior segment single scan (limbus to limbus; eight frames per second). To capture the dynamic change of the angle configuration in response to dark–light changes, video recording software (CamStudio 2.1; Rendersoft Software; Singapore) was installed in the Visante computer with one frame recorded every 5 msec (the default recording rate). OCT imaging was performed with the protocol anterior segment single 0° to 180° (6 mm deep x 16 mm wide, with 256 A-scans per line). The scan line was manually adjusted to bisect the pupil. Video recording began once the subject had been dark adapted for about 1 minute. The room light was then turned on (light intensity measured at the subject sitting position = 368 lux). The change in pupil size, from dilation in darkness to constriction under room light, and the associated changes in angle configuration, were recorded in a video file, which was subsequently exported for editing. Each video file was reviewed with video editing software (Video Edit Magic version 4.21; Deskshare, Plainview, NY). Depending on the recording time, which varied among subjects, each video file contained 600 to 1000 images. Only the portion of images showing the smooth transition of pupil size from the dark to the light was used for the analysis. Because the video capture rate is high (the default rate is 5 msec), there were many identical images during the video capture. As we could not pinpoint where the changes occur in the image series, rather than using the approach of systematic sampling, we examined all the images to prevent skipping and missing potentially useful images showing changes in pupil size and angle configuration. Each image series was reviewed in the video editing software frame by frame, beginning from a fully dilated to a constricted pupil. Since the images were sequentially reviewed in the same viewing window, any subtle change in the images, including change in pupil size, could be detected easily by flipping the images back and forth. In other words, if there is no change in the angle configuration or pupil size, the images would appear as "static" despite changing the frames. During the video capture, any microsaccade or eye movement can be detected, both in the real-time camera and in the OCT panel, as movement of the whole eyeball, and not just the iris tip. Therefore, one can easily differentiate whether it is the movement of the iris tip or the whole eyeball. If there is microsaccade and eye tremor observed during the video capture, the capture was repeated. Since the duration for the pupil to change from a dilated to a constricted state was only a few seconds, it is not difficult for subjects to have steady fixation during this short period.
Measurement of AOD and TISA
We specifically wrote a program (in MatLab ver. 6.5; The MathWorks, Natick, MA) to measure the AOD500 and TISA500. The AOD500 was calculated as the distance from the corneal endothelium to the anterior iris surface perpendicular to a line drawn at 500 µm from the scleral spur. The TISA500 is an area bound anteriorly by the AOD500, 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.3 This parameter was used instead of the angle recess area (ARA500) because it has been proposed that the ARA may be less sensitive in identifying narrow angles in eyes with deep angle recess.3 The program requires the user to input the location of the scleral spur. The AOD500 and TISA500 are then calculated automatically. High repeatability (intraclass correlation [AOD500] = 0.98 [95% CI: 0.96–0.99] and intraclass correlation [TISA500] = 0.98 [95% CI: 0.96–0.99]; three measurements in a single visit) and reproducibility (intraclass correlation [AOD500] = 0.95 [95% CI: 0.90–0.97] and intraclass correlation [TISA500] = 0.94 [95% CI: 0.88–0.97]; three measurements in three separate visits) were demonstrated with the AOD500 and TISA500 measurement in a separate study in 25 subjects (Li HT et al., unpublished data, 2007).
Statistics
Statistical analysis was performed with commercial software (SPSS version 11.0; SPSS, Chicago, IL). Comparisons of the biometry parameters (axial length, spherical equivalent, axial length, and anterior chamber depth) and the AOD/TISA measurements between the open- and narrow-angle groups were performed with an independent t-test. The correlations between dark-room gonioscopy grading and the AOD500/TISA500 were expressed as a Spearman's rank correlation coefficient. Univariate and multivariate regression analyses were performed to determine factors (age, dark-room gonioscopy grading, spherical equivalent, axial length, and anterior chamber depth) related to the AOD difference (AOD500(light) – AOD500(dark)) and TISA difference (TISA500(light) – TISA500(dark)). Factors significant at P < 0.05 were included in the multiple linear regression analysis. The relationship between AOD500/TISA500 and pupil diameter in each eye was studied with linear regression analysis, and the association was expressed as a Pearson correlation coefficient.
| Results |
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| Discussion |
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The differences in anterior chamber angle measurements both in light and dark conditions have been previously investigated with UBM. Woo et al.7 found the AOD500 to be significantly greater in the light than in the dark, with a mean difference of 89 µm in 24 patients with pupillary block. UBM has also been recommended for provocative testing to determine whether an angle is occludable, as appositional closure was more frequently detected in the dark.8 With the use of the Visante OCT, our results are in agreement with previous UBM studies. The AOD500 and TISA500 in the light were significantly greater than that in the dark. Given the observation that the range of the AOD/TISA difference (AOD500/TISA500(light) – AOD500/TISA500(dark)) were large (13–817 µm for AOD; 0.011–0.154 mm2 for TISA), it is conceivable that the corresponding discrepancy in gonioscopy grading could also vary considerably. In some cases, gonioscopy assessment could be minimally affected by dark–light changes, whereas in others, the grading could change substantially (up to an AOD/TISA difference of 817 µm/0.154 mm2) depending on the effect of background illumination on the pupil size. In most population studies on glaucoma prevalence, gonioscopy was performed at a low level of ambient illumination for practical reasons9 10 11 although dark-room gonioscopy was performed in some other studies.12 13 Our results demonstrate the importance of standardizing the background light intensity in the evaluation of anterior chamber angle configuration. The effect of ambient–slit lamp illumination on the pupil size could be influential in the determination of the angle width and its measurement. Multivariate regression analysis indicated that deeper anterior chamber depth was significantly associated with a larger difference in the AOD (AOD500(light) – AOD500(dark)) and TISA (TISA500(light) – TISA500(dark)). Although a shallow anterior chamber is a risk factor for development of angle closure, caution should also be exercised when performing gonioscopy in subjects with normal or deep anterior chambers, because more variation in the assessment of angle width would be expected.
Different patterns (Fig. 1) were observed in the dynamic profile describing the relationship between AOD500/TISA500 and pupil size. The AOD500 and TISA500 decreased linearly (median Pearson correlation coefficient = –0.93 for both AOD500 and TISA500) with increasing pupil size in most cases. It is estimated that for each millimeter change in pupil size, there is an average of a 94-µm change in the AOD500 and 0.035 mm2 change in the TISA500. In contrast, the AOD and TISA remained essentially constant and independent of pupil size in an eye with relatively deep angle recess (Fig. 1b) . Dim light is one of the precipitating factors in acute angle closure. With the dynamic analysis of the anterior chamber angle profiles, we showed that appositional closure could occur before the pupil was maximally dilated in the dark (Fig. 1c) . One of the characteristic signs associated with acute angle closure is a "mid-dilated" pupil. The dark–light dynamic capture illustrates that appositional angle closure could be developed in an eye with a mid-dilated pupil.
We found that the slope of the linear regression between AOD/TISA and pupil size was higher in eyes with open angles than in those with narrow angles. In other words, for each millimeter increase in pupil size, the angle width decreased more in the eyes with open angles than in those with narrow angles. This interesting finding suggests that the iris is probably more "dynamic" in eyes with open angles than in narrow angles. Appositional closure likely occurs in eyes with short initial iridocorneal distance.
Because the objective of this study was to describe the dynamic dark–light changes of the anterior chamber angle with a new technology, we focused only on the nasal angle for analysis. Although no significant difference in AOD among superior, nasal, inferior and temporal quadrants, in either the light or the dark, was found in a previous UBM study,7 it is possible that different patterns of angle dynamics in response to dark–light changes may be found in different quadrants. Of note, scanning the superior and inferior angles with the Visante OCT could be difficult because manipulation of eyelids would be required to expose the limbus for the imaging. With the use of a signal source of a super luminescent diode (SLD) with a wavelength of 1310 nm, it was not possible to investigate the dynamic changes of the ciliary body position in relation to the angle with the Visante OCT. Nevertheless, the Visante OCT was able to provide high-quality images of the angle width. Although it is mentioned in the operating manual that the wavelength of the visual aiming beam is 845 nm, there are no data available in the literature or from the company that indicate to what extent the luminance of the internal fixation light affects pupillary response. It is uncertain whether images captured in the dark by the anterior segment OCT could reflect the "true" pupillary response in darkness.
It is yet to be investigated whether the angle configuration continues to change after the pupil becomes constricted. Continued aqueous humor formation will inflate the posterior chamber until the pressure difference between the anterior chamber and the posterior chamber is in equilibrium with the resistance to flow in the channel between the iris near the pupil and the lens.
Instead of standardizing the pupil size with adjustment of different light intensity, the use of the current video capture technique allows a rapid assessment of the angle dynamics. However, images available for analysis were limited by the scan speed of the instrument and the speed of individual pupillary response. In this study, the average number of images available for analysis in each eye was 8.1 (range: 5–13 images). Although this information may not be adequate to describe nonlinear relationships, the high values of the correlation coefficient in most eyes in our series suggested that the AOD/TISA decreased in essentially a linear fashion with increasing pupil size. Because the selection of images for analysis were based on the changes of angle or iris configuration observed in the captured image series, it may have been difficult to detect iris motion when there was subtle eye movement. Nevertheless, video capture would have been repeated if a microsaccade and eye tremor had been observed. Because of the scan geometry of the scan probe and the refraction at smooth surfaces of the eye, a built-in dewarping algorithm is incorporated in the Visante OCT to correct for image misalignment. This correction, however, was not available when images were directly analyzed from video capture. Precise measurement of the anatomic changes requires removal of the optical distortion, and it is unknown how much the dewarping influences the angle measurement. Nevertheless, we believe the impact would be minimal in the study of the relationship between AOD/TISA and pupil size.
In summary, the anterior segment OCT can provide a noncontact approach to analyze the dynamic dark–light changes of the anterior chamber angle. Our results demonstrate the impact of lighting conditions during anterior chamber angle assessment and the different patterns of dynamic profile of the anterior chamber angle. Studying the dark–light dynamic profile of the angle may provide a more comprehensive assessment of individual risks of development of primary-angle closure and may enhance our understanding of the pathophysiology involved in different types of angle closure glaucoma.
| Footnotes |
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RW received research support in the form of instruments from and is a consultant for Carl Zeiss Meditec, Inc. CKSL has received an honorarium from Carl Zeiss Meditec, Inc. for a conference presentation.
Submitted for publication January 4, 2007; revised March 30, April 22 and 25, and May 27, 2007; accepted July 6, 2007.
Disclosure: C.K.-s. Leung, Carl Zeiss Meditec, Inc. (R); C.Y.L. Cheung, None; H. Li, None; S. Dorairaj, None; C.K.F. Yiu, None; A.L. Wong, None; J. Liebmann, None;R. Ritch, None; R. Weinreb, Carl Zeiss Meditec, Inc. (C, F); D.S.C. Lam, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C.
1734 solely to indicate this fact.
Corresponding author: Christopher Kai-shun Leung, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, 147K Argyle Street, Hong Kong; tlims00{at}hotmail.com.
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