Purpose
To evaluate the anterior segment biometric changes measured by anterior segment optical coherence tomography (AS-OCT) in acute primary angle closure (APAC) after laser peripheral iridotomy (LPI).
Design
Prospective interventional study.
Methods
In this clinic-based study, 52 eyes of 52 patients with resolved APAC attack who underwent LPI were enrolled. Subjects underwent complete ophthalmic examination and AS-OCT imaging before and 6 weeks after LPI. Anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness (IT), iris area, iris curvature, lens vault (LV), anterior vault, angle opening distance (AOD500, AOD750), and trabecular iris space area (TISA500, TISA750) were measured in qualified images and compared before and after LPI. A linear mixed-model analysis was performed for potential predictors of change in AOD750. Main outcome measure was change in AOD750 after LPI.
Results
The mean age of participants was 60.7 ± 9.2 years. Mean angle width (Shaffer grade) changed from 0.25 ± 0.34 at baseline to 1.22 ± 0.86 after LPI ( P < .001). However, 25 nasal angles (48.0%) and 28 temporal angles (53%) had iridotrabecular contact after LPI. All angle parameters (AOD500, AOD750, TISA500, TISA750; P ≤ .03), ACD ( P = .001), and ACA ( P < .001) increased significantly after LPI. Iris curvature and LV were reduced ( P = .01 for both) after LPI, but there was no significant change in IT and iris area. After multivariate analysis, pre-LPI AOD750 was the only factor associated with change in AOD750 (β = −0.992, P = .02). Exaggerated LV, defined as LV greater than one-third of the anterior vault (sum of LV and ACD), was present in 61.5% of the cases (32 eyes). The extent of change in angle parameters was not significantly different between groups with and without exaggerated LV after LPI.
Conclusion
This study confirms that LPI results in a significant increase in the angle width, ACD, and ACA as well as flattening of the iris in APAC eyes. The extent of angle deepening is inversely related to baseline angle width. The lens shifts posteriorly after resolution of attack, especially in those with greater lens vault.
Primary angle closure disease is characterized by a crowded anterior segment and synechial or appositional closure of the angle. Angle closure can have several different presentations. Acute primary angle closure (APAC) is characterized by sudden intraocular pressure (IOP) rise and its consequences, such as corneal edema, decreased vision, seeing halos around lights, sluggish mid-dilated pupil, headache, eye pain, and eye redness. This condition is an ophthalmologic emergency; untreated, APAC may lead to potentially sight-threatening complications. Its treatment has 2 arms: IOP reduction and relief of angle closure. The most common underlying mechanism of primary angle closure in this presentation is pupil block, which can be relieved with laser peripheral iridotomy (LPI) in most cases.
A lens-induced mechanism in the development of APAC has also been suggested. Lens vault (LV) is an important anatomic risk factor and was previously regarded as one of the strongest predictors of primary angle closure glaucoma (PACG). This mechanism of angle closure, called the “exaggerated lens vault mechanism,” was found to be predominant in half of APAC eyes in a study by Moghimi and associates.
Although various investigators have studied factors predicting LPI success in drainage angle opening among patients with primary angle closure/suspect, few studies are performed on APAC eyes with a high proportion of exaggerated LV. The present study evaluates the effect of LPI on anterior segment morphology and investigates potential predictors of LPI success in angle opening in terms of gonioscopy and biometric findings.
Methods
The study protocol was approved by the institutional review board of Farabi Eye Hospital, Tehran, Iran. This was a prospective study in which, after complete explanation, all patients gave written informed consent to participate in this research protocol.
The participants were recruited from the glaucoma clinic of Farabi Eye Hospital, Tehran, Iran, which is a tertiary care center, as part of the Farabi Angle Closure Study. All patients had an APAC attack, defined by the presence of the following: (1) at least 2 of the following symptoms of an acute episode of IOP rise: ocular pain or headache, nausea or vomiting, decreased vision, and rainbow-colored halos around lights; (2) IOP at presentation of at least 30 mm Hg by Goldmann applanation tonometry; (3) examination findings such as conjunctival injection, corneal epithelial edema, fixed mid-dilated pupil, and shallow anterior chamber; and (4) shallow anterior chamber and narrow angle in the other eye. APAC attacks were broken within 24 hours of the onset of symptoms with intravenous mannitol or oral glycerin, oral acetazolamide, and topical timolol. The APAC attack was defined as broken when IOP was less than 21 mm Hg (with or without medication) and when signs and symptoms of acute IOP rise had subsided. Eyes whose attack could not be broken with these medications were excluded from the study and received further interventions.
Individuals with history of ocular trauma, uveitis, surgery, or laser therapy were excluded from the study. Eyes with iris or angle neovascularization, pseudoexfoliation, secondary angle closure, or any iris or corneal abnormalities were also excluded. Miotic or mydriatic medications were not used in any of the patients prior to imaging.
Slit-lamp examination of the anterior segment, Goldmann applanation tonometry, and gonioscopy (with and without indentation) in dark conditions, using a Zeiss-style 4-mirror goniolens (Model G-4; Volk Optical, Mentor, Ohio, USA) with a narrow 1-mm beam of light were conducted for all the patients before LPI and 6 weeks later. The Shaffer grading system was used to evaluate the angle on gonioscopy. The angle was considered “closed” when posterior trabecular meshwork was not visible on gonioscopy of that quadrant.
Anterior Segment Optical Coherence Tomography
Anterior segment optical coherence tomography (AS-OCT) (Visante OCT; Carl Zeiss Meditec, Dublin, California, USA) was performed before LPI and again 6 weeks later in dark ambient lighting. Scans were centered on the pupil and were obtained along the horizontal axis using the Enhanced Anterior Segment Single protocol. Three images were captured, and the highest-quality image was used for analysis using the Zhongshan Angle Assessment Program (ZAAP; Zhongshan Ophthalmic Center, Guangzhou, China).
Two experienced ophthalmologists (S.M., M.M) determined scleral spur location in each image. The principal investigator (S.M.) validated all the images for quality and scleral spur location. After identifying the scleral spur, the software automatically measures anterior segment parameters, including anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness (IT), iris area, iris curvature, LV, lens thickness, and anterior vault (AV); and angle parameters, including angle opening distance at 500 and 750 μm from the scleral spur (AOD500, AOD750) and trabecular iris space area at 500 and 750 μm from the scleral spur (TISA500, TISA750). Table 1 demonstrates the definitions of the AS-OCT anterior segment and angle parameters analyzed in this study.
| Parameter | Definition |
|---|---|
| Angle opening distance at 500 and 750 μm (AOD500, AOD750) | The distance between the posterior corneal surface and the anterior iris surface on a line perpendicular to the trabecular meshwork, 500 and 750 μm from the scleral spur, respectively |
| Trabecular iris space area at 500 and 750 μm (TISA500, TISA750) | The surface area of a trapezoid with the following boundaries: anteriorly, the angle opening distance at 500 or 750 μm from the scleral spur; posteriorly, a line drawn from the scleral spur perpendicular to the plane of the inner scleral wall to the iris; superiorly, the inner corneoscleral wall; and inferiorly, the iris surface |
| Anterior chamber depth (ACD) | The axial distance from the corneal endothelium to the anterior lens surface |
| Anterior chamber area (ACA) | The cross-sectional area of the anterior chamber bordered by the posterior surface of the cornea, the anterior surface of the iris, and the anterior surface of the lens within the pupil |
| Iris area (I-Area) | Region defined as the cross-sectional area of the iris from the scleral spur to the pupil |
| Iris curvature (I-Curv) | The perpendicular distance from a line between the most central to the most peripheral points of the iris pigment epithelium to the posterior iris surface at the point of greatest convexity |
| Iris thickness (IT) | Iris thickness at 750 μm from the scleral spur (IT750) |
| Lens vault (LV) | The perpendicular distance from the anterior pole of the lens to the horizontal line between the scleral spurs |
| Anterior vault (AV) | The perpendicular distance from the corneal endothelium to the horizontal line between the scleral spurs |
The AS-OCT images were also assessed grossly for the presence and extent of iridotrabecular contact. The angles were classified as “closed” if there was iridotrabecular contact anterior to the scleral spur and “open” if there was visible space between the iris root and trabecular meshwork.
The eyes were classified as having an “exaggerated LV” if the LV was greater than one-third of the anterior vault, which is the distance between the posterior corneal surface and the line connecting the scleral spurs.
All patients underwent LPI as standard medical care within 48 hours of the onset of the APAC attack. Patients with prior LPI were excluded. The pupil was constricted with pilocarpine 2%, and LPI was performed using the ophthalmic neodymium–yttrium-aluminum-garnet (Nd:YAG) laser (Laserex Tango Nd:YAG; Ellex Medical, Adelaide, Australia) and an Abraham iridotomy contact lens. Finally, all eyes underwent dilated fundus examination including stereoscopic examination of the optic nerve head.
Statistical Analysis
Statistical analysis was performed using SPSS software version 17 (SPSS Inc, Chicago, Illinois, USA).
Pre-LPI and post-LPI gonioscopy grades were compared using the χ 2 test. Nonparametric tests were used for all statistical analysis. Comparison of mean values before and after LPI was performed using Wilcoxon signed rank for nonparametric data. Baseline AS-OCT parameters and their changes at 6 weeks after LPI were compared between the Exaggerated and Nonexaggerated LV groups using the Mann-Whitney U test.
A linear mixed-effects model was used to compare changes in AOD750 between the nasal and temporal angles and to estimate the relationship between AOD750 changes and potential influential factors. The random effect was the individual study participants; the fixed effects were age, sex, amount of peripheral anterior synechiae (PAS), AL, lens thickness, AOD750, AOD500, and other AS-OCT variables. Univariate regression was performed between potential confounders and change in AOD750. Those variables with P < .20 and variance inflation factor less than 3 were included in the final multivariate model, along with age and sex. A P value of less than .05 was considered statistically significant.
Results
Fifty-nine eyes of 59 patients with broken APAC attacks were enrolled in the study. Seven cases were excluded owing to loss to follow-up (4 cases) or unclear visualization of the scleral spur in AS-OCT images (3 cases). Data from 52 patients (37 female, 15 male) were used for the analysis. The mean age was 60.7 ± 9.2 years (range, 45–88). Mean IOP was 45.0 ± 12.1 mm Hg at presentation and reduced to 11.87 ± 5.15 mm Hg after the attack was broken. Mean Lens Opacities Classification System score for lens nucleus opacification was 2.78 ± 0.84. The mean axial length and lens thickness were 21.91 ± 1.11 and 5.03 ± 0.45 mm, respectively.
Prior to LPI, 49 of 52 (94%) nasal, 45 of 52 (87%) temporal, 45 of 52 (88%) superior, and 49 of 52 (94%) inferior angles were gonioscopically closed before LPI. After LPI, 28 of 52 (54%) nasal, 26 of 52 (50%) temporal, 42 of 52 (72%) superior, and 29 of 52 (56%) inferior angles were still closed. The mean gonioscopic grade was 0.25 ± 0.34 and increased to 1.22 ± 0.86 after LPI ( P < .001).
Based on the extent of iridotrabecular contact in AS-OCT images, nasal and temporal angles were closed in 44 of 48 (91%) and 43 of 51 (84%) angles, respectively. After LPI, 25 of 52 (48%) nasal quadrants and 28 of 52 (54%) temporal quadrants remained closed ( P = .007 and P = .003, respectively).
Both nasal and temporal angle parameters increased significantly after LPI ( Table 2 ). Although ACD and ACA increased significantly after LPI ( P = .002 and P < .001, respectively), there was no significant change in anterior vault. Lens vault decreased at post-LPI visit and the amount of change was associated with preoperative LV (ß = −0.127, P = .04). The mean iris curvature was 0.30 ± 0.11 mm before LPI and decreased to 0.22 ± 0.13 mm after LPI ( P = .01) ( Table 2 ). However, there was no significant change in IT750 or iris area.
| Variable | Pre-LPI | Post-LPI | P Value |
|---|---|---|---|
| Anterior segment parameters | |||
| ACD (mm) | 1.81 ± 0.24 | 1.86 ± 0.19 | .001 ∗ |
| Lens vault (μm) | 1081.1 ± 265.9 | 1051.7 ± 256.9 | .01 ∗ |
| ACA (mm 2 ) | 12.53 ± 1.84 | 13.25 ± 1.88 | <.001 ∗ |
| Anterior vault (mm) | 2.89 ± 0.23 | 2.91 ± 0.20 | .37 |
| Iris parameters | |||
| IT750 (mm 2 ) | 0.49 ± 0.08 | 0.47 ± 0.11 | .97 |
| I-Curve (mm) | 0.30 ± 0.11 | 0.22 ± 0.13 | .01 ∗ |
| I-Area (mm) | 1.49 ± 0.31 | 1.46 ± 0.31 | .98 |
| Nasal angle | |||
| AOD500 (μm) | 0.030 ± 0.052 | 0.066 ± 0.069 | <.001 ∗ |
| AOD750 (μm) | 0.053 ± 0.074 | 0.112 ± 0.094 | .001 ∗ |
| TISA500 (μm 2 ) | 0.017 ± 0.028 | 0.030 ± 0.030 | .03 ∗ |
| TISA750 (μm 2 ) | 0.028 ± 0.041 | 0.054 ± 0.050 | .009 ∗ |
| Temporal angle | |||
| AOD500 (μm) | 0.031 ± 0.049 | 0.093 ± 0.082 | <.001 ∗ |
| AOD750 (μm) | 0.057 ± 0.068 | 0.142 ± 0.108 | .01 ∗ |
| TISA500 (μm 2 ) | 0.013 ± 0.021 | 0.039 ± 0.035 | <.001 ∗ |
| TISA750 (μm 2 ) | 0.025 ± 0.034 | 0.070 ± 0.055 | <.001 ∗ |
In the linear mixed model, only angle parameters (AOD750 and AOD500) were significantly correlated with change in AOD750. In the final multivariate model adjusting for age, sex, and confounders with P < .20 in univariate analysis and variance inflation factor less than 3, the only significant predictor of angle opening was AOD750 (β = −0.704, P = .02) ( Figure ) Change in AOD was not associated with age, sex, axial length, iris parameters (iris thickness, area, or curvature), anterior segment parameters (ACD, ACA, LV, lens thickness, and anterior vault), or amount of PAS ( Table 3 ).
| Variable | Univariate Analysis | Multivariate Analysis a | ||
|---|---|---|---|---|
| B (95% Confidence Interval) | P Value | B (95% Confidence Interval) | P Value | |
| Age (y) | −0.004 (−0.002 to 0.001) | .71 | 0.0008 (−0.003 to 0.001) | .44 |
| Sex (F/M) | −0.003 (−0.057 to 0.050) | .88 | −0.024 (−0.072 to 0.024) | .41 |
| PAS | 0.0002 (0.0001–0.0006) | .19 | 0.0006 (−0.0002 to 0.0003) | .64 |
| Axial length (mm) | −0.005 (0.028–0.017) | .62 | – | – |
| ACD (mm 2 ) | −0.015 (−0.094 to 0.126) | .77 | – | – |
| Lens thickness (mm) | −0.030 (−0.082 to 0.240) | .26 | – | – |
| ACA (mm 2 ) | −0.001 (−0.012 to 0.009) | .73 | – | – |
| Lens vault (μm) | 0.0002 (−0.0007 to 0.0001) | .27 | – | – |
| Relative lens vault | −0.089 (−0.234 to 0.413) | .58 | – | – |
| Anterior vault | 0.521 (−0.544 to 0.158) | .33 | – | – |
| Iris parameters | ||||
| IT750 (mm) | 0.005 (−0.042 to 0.054) | .80 | – | – |
| I-Area (mm 2 ) | −0.002 (−0.033 to 0.1029) | .86 | – | – |
| I-Curve (mm) | −0.005 (−0.110 to 0.098) | .91 | – | – |
| Angle parameters | ||||
| AOD750 (μm) | −0.599 (−0.895 to −0.303) | <.001 ∗ | −0.992 (−1.937 to −0.048) | .02 ∗ |
| AOD500 (μm) | −0.622 (−1.045 to −0.199) | .005 ∗ | 0.907 (−0.252 to 2.067) | .12 |
a Including age, sex, and those variable with P < .20 in univariate analysis and variance inflation factor less than 3.
Exaggerated LV was present in 61.5% of the cases (32 of 52 eyes) before LPI. The relative LV ratio, calculated as LV divided by the sum of LV and ACD, was 0.41 ± 0.05 in the Exaggerated LV group and 0.26 ± 0.03 in the Nonexaggerated LV group ( P < .001) ( Table 4 ).
| Variable | Exaggerated Lens Vault (N = 32) | Nonexaggerated Lens Vault (N = 20) | P Value |
|---|---|---|---|
| Age (y) | 63.2 ± 9.7 | 56.3 ± 6.7 | .009 ∗ |
| Sex (F/M) | 25/7 | 12/8 | .13 |
| Nuclear opacity (LOCS III) | 3.00 ± 0.79 | 2.46 ± 0.83 | .05 ∗ |
| PAS | 66.4 ± 107.3 | 77.5 ± 126.8 | .97 |
| Axial length (mm) | 21.75 ± 1.33 | 22.14 ± 0.62 | .32 |
| ACD (mm) | 1.68 ± 0.16 | 2.03 ± 0.19 | <.001 ∗ |
| ACA (mm 2 ) | 11.70 ± 1.32 | 13.84 ± 1.82 | <.001 ∗ |
| Lens thickness (mm) | 5.25 ± 0.42 | 4.71 ± 0.31 | <.001 ∗ |
| Lens vault (μm) | 1206.7 ± 214.0 | 814.4 ± 121.1 | <.001 ∗ |
| Anterior vault (mm) | 2.89 ± 0.24 | 2.84 ± 0.21 | .48 |
| Iris parameters | |||
| IT750 (mm) | 0.49 ± 0.09 | 0.65 ± 0.08 | .92 |
| I-Area (mm 2 ) | 1.49 ± 0.33 | 1.49 ± 0.30 | .19 |
| I-Curve (mm) | 0.31 ± 0.11 | 0.27 ± 0.11 | .90 |
| Nasal angle | |||
| AOD500 (μm) | 0.026 ± 0.035 | 0.036 ± 0.072 | .40 |
| AOD750 (μm) | 0.041 ± 0.040 | 0.073 ± 0.108 | .92 |
| TISA500 (μm 2 ) | 0.019 ± 0.026 | 0.015 ± 0.032 | .55 |
| TISA750 (μm 2 ) | 0.028 ± 0.032 | 0.030 ± 0.053 | .73 |
| Temporal angle | |||
| AOD500 (μm) | 0.033 ± 0.041 | 0.028 ± 0.061 | .73 |
| AOD750 (μm) | 0.049 ± 0.044 | 0.071 ± 0.094 | .92 |
| TISA500 (μm 2 ) | 0.016 ± 0.020 | 0.010 ± 0.010 | .65 |
| TISA750 (μm 2 ) | 0.026 ± 0.028 | 0.024 ± 0.024 | .98 |
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