Ang, Ghee Soon MBChB, FRCOphth; Wells, Anthony P. FRANZCO
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide, particularly in the Asian population.1,2 Even amongst the White population, in whom the commonest form of glaucoma is of the open variety, PACG may not be as rare as previously considered.3,4 An important component of the treatment for PACG is laser peripheral iridotomy (PI), which relieves pupil block and thus flattening the iris contour and widening the drainage angle.5–12 However, laser PI is not always successful in widening the drainage angles, with imaging studies reporting residual angle closure in up to 60% of cases post-PI.5–7,13–15 Most studies evaluating the structural differences between eyes with successful angle widening and persistent angle closure were performed based on ultrasound biomicroscopy (UBM) imaging after the laser PI had been performed. The aim of this study was to use anterior segment optical coherence tomography (AS-OCT) to determine the pre-PI anatomical differences in eyes which had residual angle closure and those which did not after laser PI.
MATERIALS AND METHODS
This was a retrospective case series of White patients who underwent laser PI for angle closure at Capital Eye Specialists, Wellington. Consecutive patients were identified from the electronic patient database as having undergone laser PI from November 2007 to November 2009. Each patient with suspected narrow angles (NAs) received a full ophthalmic assessment including best-corrected Snellen acuity, slit lamp evaluation, Goldmann applanation tonometry, corneal pachymetry, corneal hysteresis measurement, undilated fundoscopy, gonioscopy, and AS-OCT imaging. Indentation gonioscopy was conducted in dark conditions, and careful note was taken to document the presence and extent of peripheral anterior synechiae (PAS).
AS-OCT was performed with the slit lamp OCT (Heidelberg Engineering, GmBH, Dossenheim, Germany) in light and with all room lights and slit lamp illumination switched off (dark). Scans of the horizontal meridian were performed first, followed by scans of the vertical meridian. The scans were conducted by 2 experienced ophthalmic technicians who had been trained to perform AS-OCT imaging in the same, standardized manner. All 4 quadrants of the AS-OCT scan were reviewed by the glaucoma specialist (A.P.W.) to determine if laser PI was indicated. The indication for laser PI was apposition between the iris and trabecular meshwork anterior to the scleral spur in 2 or more quadrants in dark conditions, as seen on AS-OCT imaging. This AS-OCT threshold is based upon the gonioscopic criteria for laser PI from the Association of International Glaucoma Societies consensus on angle closure.16 These patients were considered to have NA. Primary angle closure (PAC) occurred if the NA was associated with PAS and/or intraocular pressure (IOP) of greater than 21 mm Hg. If there were concurrent optic disc features characteristic of glaucoma, with or without visual field changes, then the diagnosis of PACG was made. We excluded eyes with secondary angle closure (such as angle neovascularization, trauma, and intumescent cataract), previous intraocular surgery, and previous laser iridoplasty and/or laser PI. Only the right eye was used for analysis if both eyes were eligible.
After pupil constriction was achieved with pilocarpine 2%, laser PI was performed using the ophthalmic neodymium: yttrium aluminium garnet laser (Laserex Tango Nd:YAG, Ellex Medical, Australia) and an Abraham iridotomy contact lens. The PI was placed as close to the 12 o’clock meridian as possible and as far peripherally as practical. Full-thickness perforation was confirmed by the gush of pigment and aqueous from the posterior chamber into the anterior chamber. After laser PI, patients were given topical prednisolone acetate 0.12% for 5 days.
At the follow-up visit, the AS-OCT imaging was repeated with the above technique. The laser PI was deemed to have been unsuccessful if there was still peripheral apposition between the iris and trabecular meshwork in 2 or more quadrants when imaged in the dark. In other words, the PI was considered successful when the amount of iridotrabecular apposition anterior to the scleral spur was ≤1 quadrant in the dark. The clinical decision as to whether or not the PI had been successful was made by the glaucoma specialist (A.P.W.) based on the AS-OCT images of all 4 quadrants, using the same criteria as for deciding whether or not to perform laser PI.
With the AS-OCT scanning, although images of all 4 drainage angle quadrants were captured, only horizontal images were selected for analysis. Images were required to have a clear view of the scleral spur, iris recess and structures, pupil, lens, cornea, and scleral edges The measurements of the nasal and temporal quadrants was performed by only one observer (G.S.A.), who was masked to the outcome of laser PI. The following parameters were calculated by the in-built analysis software once the locations of the scleral spur and iris recess apex were selected: anterior chamber depth (ACD), trabecular-iris angle (TIA), angle opening distance (AOD), and trabecular-iris space area (TISA). Parameters that were not included in the in-built analyses were measured manually: trabecular-iris contact length (TICL), iris thickness (IT) and maximal iris bow height (MIBH).
The ACD was the distance from the apex of the anterior pole of the crystalline lens to the apex of the posterior corneal surface. The TIA 500 was the angle between the point of the trabecular meshwork 500 μm from the scleral spur and the point on the anterior iris perpendicularly, with the apex at the iris recess.17 The AOD 500 was the perpendicular distance between the trabecular meshwork 500 μm anterior to the scleral spur and the anterior iris surface.17 The TISA 500 was the trapezoidal area bordered by the AOD 500, corneoscleral wall, anterior iris surface, and the perpendicular line from the scleral spur to the iris.18 The TICL was the length of contact between the anterior iris surface and the corneoscleral wall.18 IT 500 was the perpendicular distance from the anterior iris surface at 500 μm and from the scleral spur to the posterior iris pigment epithelial surface. The IT 750 was also measured as the distance between the points on the anterior and posterior iris surface 750 μm from the scleral spur.7 The MIBH indicated the amount of iris convexity, and was the perpendicular distance from the posterior iris pigment epithelial surface at its apex to the line joining the iris pigment epithelium at the pupil edge to its insertion at the ciliary body.19 The iris pigment epithelium was identified by the hyperreflective curve on the posterior iris surface, whereas its insertion at the ciliary body was the point where the hyperreflective curve terminated within the ciliary body. These parameters are summarized diagrammatically in Figures 1A and 1B.
To evaluate intraobserver variation, 20 eyes were randomly selected and the temporal angle parameters were remeasured by the same observer at a separate session. The intraobserver reproducibility was assessed with the intraclass correlation coefficient.
Data were analyzed using SPSS 15.0 (SPSS Inc, Chicago, IL). Basic descriptive statistics were calculated for patient demographics. Comparison of means was performed with the t test for parametric data and Mann-Whitney U test for nonparametric data. Comparison of proportions was performed with the χ2 test. In the multivariate analyses with binomial logistic regression, the angle width parameters (TIA 500, AOD 500, TISA 500, TICL) were analyzed individually according to location and illumination, along with MIBH and IT as well as the constant variables of age, sex, glaucomatous optic neuropathy, and steroid use. Statistical significance was achieved if the P value was <0.05.
Eighty-nine White patients presented for laser PI over the 25-month study duration. Eighteen (20.2%) were excluded owing to absent or unsuitable AS-OCT scans, including those where the scleral spur could not be visualized. The remaining 71 patients had a mean (±SD) age of 60.3 (±10.0) years. Of this cohort of 71 patients, 40 (56.3%) were women. Forty-eight (67.6%) were NA eyes, 9 (12.7%) were PAC eyes, and 14 (19.7%) were PACG eyes. Only 2 (2.8%) had PAS, both of which were documented not to exceed 1 quadrant. Sixty-one (85.9%) were right eyes. None had previously suffered acute PAC episodes. The PI was confirmed to be patent for all eyes at the follow-up visit; this occurred a mean of 5.9 (±3.2) weeks from the date of the PI. At this visit, the PI was considered to have been successful in 54 eyes (76.1%). Table 1 summarizes these baseline characteristics.
Between the successful and unsuccessful groups, there was a significant difference in the number of quadrants with peripheral iridotrabecular apposition in the dark (P=0.001) before laser. The proportion of those using inhaled steroids, proportion of women, and mean central corneal thickness demonstrated a trend toward significance (P=0.050, 0.055, and 0.070, respectively). The change in pupil size from light to dark conditions showed no statistically significant differences both before and after laser PI (P=0.437 and 0.078, respectively).
There was generally a significant difference in outcomes for indicators of angle width (TIA 500, AOD 500, and TISA 500) between groups when compared with the t test, but this was different for the temporal and nasal angles. For the temporal angle, only the TIA 500, AOD 500, and TISA 500 measured in light conditions showed statistical significance. All the nasal angle width parameters were significant apart from TISA 500 in light. The TICL showed significance in both angles in light and dark environments. There was disparity with the IT measurements (IT 500 and IT 750), where statistical significance was not attained in the nasal angle but was achieved in the temporal angle only in light conditions. The MIBH change in light achieved significance in the temporal angle and approached significance in the nasal angle. These parameters are summarized in Table 2. When analyzed with the binomial logistic regression model to take into account the other angle parameters and baseline characteristics, the pre-PI TIA 500, AOD 500, and MIBH in light demonstrated statistical significance between groups, whereas IT did not. The only parameter that was significantly different in both light and dark conditions for both the temporal and nasal angles was the TICL.
Table 3 summarizes the magnitude of change in the angle parameters when the illumination was altered from light to dark, ie, measurement in dark - measurement in light. After PI in the successful group, there was significantly less angle narrowing (less reduction in TIA 500 and AOD 500; less increase in TICL) when illumination was changed from light to dark. There was also less anterior iris bowing (less increase in MIBH) in the nasal angle post-PI, although no significant difference in IT was found.
All the angle parameters demonstrated moderate-to-good intraobserver reproducibility apart from TISA 500 (Table 4).
UBM and AS-OCT are 2 imaging modalities available to image the anterior chamber angle. The AS-OCT is noncontact, less operator dependent, performed upright, and has greater resolution when compared with UBM. As there is no requirement for contact, it is more comfortable and potentially safer for the patient. Furthermore, there is also less likelihood of any external pressure affecting anterior segment anatomy during imaging. AS-OCT measurements have been reported to have good reproducibility and repeatability with low interobserver variability,20–22 and are similar to UBM for quantitative angle measurements.18 In addition, its sensitivity in detecting angle closure is better when compared with gonioscopy.23
In this study, only the parameters from the temporal and nasal angles were analyzed. As AS-OCT imaging of the superior and inferior angles would involve physical eyelid manipulation in most eyes, the real possibility of external pressure resulting in distortion of the angle anatomy in the superior and inferior quadrants could not be excluded. This is particularly relevant for the present study owing to its retrospective design.
By equalizing the pressure gradient between the posterior and anterior chamber, laser PI should widen the drainage angle and reduce the amount of anterior iris bowing.5–12 However, laser PI is not always successful in achieving angle opening in dark room conditions. In a UBM-based prospective case series of 55 fellow eyes of Asian patients presenting with acute PAC, 20% still had angle closure (angle recess area 750 of 0 mm2 in ≥90 degrees) after PI.6 In a retrospective study of 70 Japanese eyes with PAC which underwent PI, 39% had residual angle closure as seen on UBM.14 The Liwan Eye Study reported that of 72 PAC suspect eyes, 59% still had UBM-identified iridotrabecular contact in ≥ 1 quadrant post-PI.7 In another study from Singapore, 32% of PAC suspect eyes after PI were found to have persistent iridotrabecular contact on UBM.13 A separate UBM study of 34 Chinese fellow eyes of acute PAC observed that despite laser PI, iridotrabecular apposition remained in at least 1 quadrant in 38%.15
The majority of imaging studies assessing persistent angle closure analyzed parameters from UBM images obtained during dark room imaging after PI.13–15 The aim of this study was to use AS-OCT to quantify any pre-PI angle biometric features in both light and dark conditions that may hold prognostic value for determining if a PI would not be successful in the short term. For the purposes of our study, we defined a closed angle as one where there was any iridotrabecular contact as seen on AS-OCT imaging.7,15 We considered the laser PI to have been unsuccessful if there was iridotrabecular contact anterior to the scleral spur in ≥ 2 quadrants in the follow-up AS-OCT scan; this was our threshold for performing laser PI in the first place. In our cohort, 23.9% (17 of 71) had an unsuccessful outcome despite patent PIs. In these cases, although laser PI has reduced or removed pupil block, presumably there must be some iris root, ciliary body, lens, and/or posterior segment factor that is still contributing to the persistent appositional angle closure.
Various imaging studies have identified features, mostly post-PI, associated with residual angle closure. Nonaka et al14 noted that persistent angle closure was more common after PI in PAC eyes with poorly controlled IOP or glaucoma damage. Persistent iridotrabecular contact was also reported to be associated with UBM features of plateau iris.13 Yao et al15 observed that fellow eyes of acute PAC with residual appositional closure had significantly lower TIA 500, AOD 500, and angle recess area in all 4 quadrants, greater IT superiorly and nasally, and decreased trabecular-ciliary process distance inferiorly and temporally when measured in the dark. Our study did not find any association between pre-PI IOP and glaucoma damage with an unsuccessful PI outcome. This was expected in our cohort owing to the small number of eyes with glaucoma and the fact that the IOP was generally already within the normal range before laser PI. Among the angle parameters that were assessed after laser PI, we also found a significant difference in the TIA 500, AOD 500, and TISA 500 both temporally and nasally when measured in the dark in eyes with persistent angle closure. However, we found no difference in IT unlike in Yao et al's report. This may partly be accounted for by the slight difference in IT measurement technique. We are unable to comment upon measurements pertaining to the ciliary body or plateau iris features because AS-OCT does not image the ciliary body in enough detail to allow us to do so.
In the Liwan Eye Study, PAC suspect eyes with ≥270 degrees appositional closure on gonioscopy after PI had shallower mean AOD and greater mean IT 1000 when assessed before laser PI in dark room conditions.7 We also found that in general, an unsuccessful PI outcome was associated with greater angle closure in terms of amount of trabecular-iris apposition and number of quadrants involved, narrower angles, and less iris bowing before laser PI was conducted. This is not surprising, because we would reasonably expect eyes with more angle closure but with less pupil block (ie, mechanisms other than pupil block being involved as well) to be less successful than if the angle closure was due to pupil block only. Figure 2 shows an example of an eye in which both the temporal and nasal angles remained closed in the dark 9.7 weeks after laser PI. In contrast to the Liwan Eye Study, we did not observe any significance for IT 500 or IT 750; this may be attributed to the different distances from which the IT was measured (we did not measure IT at 1000 μm from the scleral spur). Nevertheless, our results indicate that proximal IT is unlikely to hold any predictive value for post-PI success.
There were several interesting observations from our study. The first was the disparity between the temporal and nasal angle differences between the groups. Analysis with the t test demonstrated significance for the temporal angle parameters only in light conditions, whereas nasal angle width parameters (TIA 500, AOD 500, and TISA 500) were significant or approaching significance for the nasal angle in both light and dark conditions. On the other hand, significance was not achieved for nasal IT 500 in light, but it was in the temporal angle. The only parameter where both angles had similar results was the TICL, which was significant in both light and dark. The histological structure of the iris should be the same throughout the 4 quadrants and UBM evaluation of angle parameters had previously shown no difference in light-dark changes among the 4 quadrants for patients with NAs and pupillary block.6,19 However, the frequency of angle closure according to the different quadrants is not uniform,7 which suggests that there may be differences in regional iris behavior (static or dynamic) that may affect PI outcome.
The second interesting observation was the disparity between light-dark measurements for some of the parameters, most notably in the temporal angle, where the TIA 500, AOD 500, and MIBH measured in light conditions showed significance on logistic regression analysis. A plausible explanation is that as only eyes with iridotrabecular apposition in the dark underwent PI, it could reasonably be expected that the eyes already had narrow or closed angles in the dark before PI to begin with, regardless of the outcome. As the angles are expected to be wider under illuminated conditions, angles that are already narrow to begin with in light may reveal a predisposition toward angle closure that may not be correctable with laser PI. So while AS-OCT imaging in the dark provided the basis for whether or not laser PI was required, imaging in light provided an indication of the likelihood of success after PI.
Another interesting observation was the tendency for those with concurrent usage of inhaled steroid to have a less successful outcome after PI, although this just reached the conventional threshold of statistical significance (χ2 test; P=0.050). If this was a significant effect hinted at by an underpowered study, it could be an interesting finding. The anti-inflammatory effect of the steroid ought to reduce any edema at the choroid and ciliary body, thereby reducing the degree of angle closure if swelling was a factor. Conversely, steroid-related deposition of extracellular matrix may decrease iris permeability such that the iris is not able to lose volume in the dark sufficiently to avoid iridotrabecular apposition, which would support the iris sponge hypothesis.24,25
There are several limitations in this study, the major one being the weaknesses inherent in a retrospective study design. Selection bias could have occurred as a result of performing laser PI based only on AS-OCT findings. However, these decisions were made regardless of whether or not a response from the laser was anticipated, and identical criteria were used to judge success of the PI. As gonioscopic appearances were not documented in a standardized manner for all eyes, we could not perform any meaningful comparison between AS-OCT and gonioscopy. Furthermore, the possibility that the exact same section was not imaged at the pre-PI and post-PI visits could not be discounted, even though all AS-OCT imaging was performed with the scans centered on the pupil. In addition, as mentioned above, the posterior ciliary body could not be imaged in sufficient detail to allow measurements or confirmation of plateau iris features. Finally, as the results of this study were based on AS-OCT imaging, we were unable to comment upon the clinical effectiveness of laser PI in the prevention of future PAS.
The results of this study indicate that a significant proportion (23.9%) of White eyes still retain appositional angle closure after laser PI. Greater angle closure and reduced anterior iris bowing in light conditions was associated with post-PI residual angle closure. Longer term follow-up would provide further insight on the evolution of angle structure changes and whether or not these anatomical characteristics are also associated with late PI failure.
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