Glaucoma is the leading cause of irreversible blindness worldwide.1–3 It was estimated that 4.5 and 3.9 million people suffered from bilateral blindness due to open angle glaucoma and angle closure glaucoma respectively in 2010, and the numbers were expected to expand to 5.9 and 5.3 million in 2020.1 Compared with primary open angle glaucoma, primary angle closure disease (PACD) is more detrimental as it carries a 3-fold rate of severe bilateral visual impairment.4 Early diagnosis and prompt intervention could prevent the disease from progression and protect visual function.5
Swept-source optical coherence tomography (SS-OCT) provides better imaging quality and higher scanning speed than its traditional counterparts, enabling 3-dimensional (3D) reconstruction and accurate quantification of the anterior segment structures.6,7 In our previous research using SS-OCT (Casia SS-1000), we found that volumetric parameter, anterior chamber volume (ACV) had better performance than traditional 2-dimensional (2D) angle parameters in classification of angle width.8 However, whether anterior-segment SS-OCT-derived volumetric parameters such as ACV or iris volume (IV) were indicative of disease prognosis was unclear.
Laser peripheral iridotomy (LPI) is the most commonly used treatment for early PACD due to its safety and cost-effectiveness.9 In this study, LPI was used as a model to observe the association between anterior chamber parameters and disease prognosis, in a bid to investigate the effectiveness of 3D parameters in the follow-up of PACD.
SUBJECTS AND METHODS
This study was approved by the ethical review committee of Zhongshan Ophthalmic Center and conducted in accordance with the tenets of Helsinki Declaration. Written informed consent was obtained from each subject before the trial.
Subjects older than 40 years old diagnosed with primary angle closure suspect (PACS), primary angle closure (PAC), and PAC glaucoma (PACG) with <180 degree of peripheral anterior synechia were included. The diagnosis was based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Gonioscopy was performed by a senior expert (X.L.Z.) in a dark room with low ambient lighting. Patients who had experienced miosis or mydriasis within a month had to wash out for 2 weeks before inclusion. Exclusion criteria were listed as follows:
- 1) Secondary angle closure caused by lens subluxation or dislocation, uveitis, neovascular glaucoma, and so forth;
- 2) History of ocular surgery or laser therapy;
- 3) Previous episode of acute attack;
- 4) Other ocular comorbidities, such as maldevelopment of anterior segment, nanophthalmos, ocular trauma, fundus diseases, and so forth.
Patients underwent Goldmann applanation tonometry, slit lamp microscopy, fundus examination with 90D lens, autorefractometry, OCT scan, and static automated perimetry (SITA standard algorithm with a 24–2 test pattern; Humphrey Visual Field Analyzer, Carl Zeiss Meditec) before and at 1 week, 1 month, 3 months, 6 months, 1 year after LPI. Anti-glaucoma eye drops were prescribed whenever intraocular pressure (IOP) rose to above 21 mm Hg, and the patient came back to the hospital one week later for IOP measurement. Brinzolamide or timolol was prescribed separately or in combination according to the extent of IOP elevation.
Sequential argon and ND:YAG laser was used to perform LPI. Two percent of pilocarpine was instilled before treatment. The laser incision was made between 10 o’clock and 12 o’clock in the right eye and between 12 o’clock and 2 o’clock in the left eye. The power of argon laser was set at 300mW to 500mW, with the duration being 0.10 s and laser spot ranging between 50 and 100 μm. The power of Nd:YAG laser was 4mJ to 6mJ. Topical dexamethasone solution four times and timolol eyedrop twice a day were prescribed after LPI for a week. No severe complications were observed after the surgery.
Casia SS-1000 (Tomey, Nagoya, Japan) was used to image the anterior segment at each time point of follow up. Swept source optical coherence tomography (OCT) examination was performed in a standardized darkroom (0.16 lux) by 2 experienced technicians who were blind to clinical information of the patients. The criteria for acceptable images include clear visualization of the scleral spur (SS), angle, and iris. If there were images of which could not be recognized, images within 5 degrees were checked to see whether the SS was discernible so that the images could be fully taken advantage of. Otherwise, the image was excluded from analysis. The anterior segment was scanned using the “angle analysis” mode. “Angle analysis” mode contains 128 radial B-scans. ACV and IV were calculated respectively by adding up the anterior chamber area (ACA) and iris area (IA) of the 128 meridians together automatically by the built-in software (Ver.7J.8.). IA was defined as the area bordered by anterior surface of the iris and the iris pigment epithelium. ACA was defined as the area bordered by corneal endothelium, anterior surface of iris, and the lens. TISA750 at 3, 6, 9, and 12 o’clock was measured separately. After manually marking the SS, other related parameters such as anterior chamber depth, lens vault, and anterior chamber width were calculated by taking the average of the horizontal and vertical scans. Pupil diameter was calculated as the distance between the pupillary margins. The borders between different structures were manually corrected if they were not along the right boundary (Fig. 1).
The data with normal distribution were presented as mean ± SD, otherwise presented as median with interquartile range. Paired t test was used to evaluate the change of specific parameters at 2 different time points. Logistic regression was used to evaluate the relationship between baseline anterior segment OCT parameters, including TISA750, ACV, IV, and occurrence of IOP elevation. All reported P values are 2-sided, and P values <0.05 were considered statistically significant.
The baseline characteristics of the participants were summarized in Table 1. Ninety eyes of 81 subjects were included, of whom 59 were female, and 22 were male, with a mean age of 60.98 ± 9.44 years. The average TISA750 (mean value of TISA750 at 3, 6, 9, and 12 o’clock), ACV, and IV were 0.04 ± 0.03 mm2, 76.38 ± 14.65 mm3, and 30.86 ± 3.70 mm3, respectively. Among all the participants, 72 subjects finished 1 year follow-up. Of the 9 participants lost to follow-up, 4 were no longer contactable, 1 passed away, 2 moved to another city and were inconvenient to come back, and 2 refused to come back.
TABLE 1 -
Baseline Characteristics of the Included Subjects
||Mean ± SD
||60.98 ± 9.44
||22.58 ± 0.68
||1.92 ± 0.24
||76.38 ± 14.65
||11.42 ± 0.28
||0.28 ± 0.08
||30.86 ± 3.70
||0.98 ± 0.22
||3.74 ± 1.06
||0.04 ± 0.03
|Diagnosis (NO. eyes)
ACD indicates anterior chamber depth; ACV, anterior chamber volume; ACW, anterior chamber width; AL, axial length; IC, iris curvature; IV, iris volume; LV, lens vault; PAC, primary angle closure; PACG, primary angle closure glaucoma; PACS, primary angle closure suspect; PD, pupil diameter; SD, standard deviation; TISA750, trabecular-iris space area 750 μm from scleral spur.
Association Analysis Between IOP Elevation and Anterior Segment Parameters
IOP elevation >21 mm Hg appeared in 14 eyes (Supplemental Table 1, http://links.lww.com/APJO/A60). New synechia in these eyes was not found under gonioscopy compared with baseline records.
In total, there were 2 images of the horizontal meridian and 3 of vertical meridian excluded. Table 2 shows the association between IOP elevation and the mean TISA750 of the 4 quadrants. Mean TISA750 was negatively associated with IOP elevation [odds ratio (OR) = 0.94, P = 0.02]. The correlation of TISA750 at inferior, superior, nasal, and temporal quadrant with IOP elevation was shown in Supplemental Table 2–5, http://links.lww.com/APJO/A60. TISA750 was only significantly associated with IOP elevation in the temporal quadrant (OR = 0.98, P = 0.046), whereas in the other 3 quadrants, there was no significant association.
TABLE 2 -
Association Between IOP Elevation and Mean TISA750
|Sex, with male as control
∗TISA750∗1000 was used to better present the result.ACW indicates anterior chamber width; AL, axial length; CI, confidence interval; IT750, iris thickness 750 μm from scleral spur; LV, lens vault; OR, odds ratio; PD, pupil diameter; TISA750, trabecular-iris space area 750 μm from scleral spur.
As shown in Table 3, greater ACV was associated with lower risk of IOP elevation (OR = 0.80, P = 0.03), whereas IV was not associated with IOP elevation (P=0.36).
TABLE 3 -
Association Between IOP Elevation and ACV and IV
|Sex, with male as control
ACD indicates anterior chamber depth; ACV, anterior chamber volume; ACW, anterior chamber width; AL, axial length; CI, confidence interval; IC, iris curvature; IOP, intraocular pressure; IV, iris volume; LV, lens vault; OR, odds ratio; PD, pupil diameter.
In this study, we showed that smaller ACV and mean TISA750 were associated with IOP elevation after LPI. However, the association between TISA750 and IOP elevation varied across quadrants and was only significant in the temporal quadrant. Our results indicated that ACV is more reliable and easier to use than angle width parameters (TISA750) in predicting the prognosis of PACD eyes after LPI.
Although gonioscopy is still the gold standard in angle classification,10 OCT is the only noncontact approach for accurate quantification of the anterior chamber structures.7 We previously demonstrated that ACV, and angle width parameters measured with Casia SS-1000, could efficiently differentiate angle closure from open angle.8 However, as far as we know, 3D parameters derived from Casia SS-1000 have not been used previously in the evaluation of long-term clinically relevant outcomes after LPI.
Most of the previous longitudinal studies evaluated change of 2D parameters, mainly focusing on angle width in PACD patients.11–13 Zhekov et al13 observed that angle open distance remained stable or increased within the 6-month follow-up, whereas Jiang et al and Lee et al found that angle width increased shortly after LPI, and decreased after 6 months.11,12 Although these studies may indicate the usefulness of 2D parameters such as angle open distance or trabecular-iris space area in documenting long-term change in PACD, the change in angle width does not necessarily represent disease progression.14 IOP elevation >21 mm Hg, however, is the most commonly used indicator of poor outcome and necessity for further intervention in the management of PACD, such as antiglaucoma medications or surgeries.15,16
An important finding of the present study is that smaller ACV and narrower angle were associated with greater likelihood of IOP increase after LPI. This is supported by Lim et al's17 finding that patients with lower Shaffer score were more likely to need IOP-lowering medications after LPI. Peng et al18 also noticed that smaller angle width was associated with increased chance of progression from primary angle closure suspect to PAC. This could be attributed to the following reasons. First, eyes with narrower angle and more crowded anterior chamber may have higher risk of intermittent angle closure, leading to IOP increase. Second, accumulated evidence suggested that magnitude of IOP reduction after lens extraction is greater in eyes with narrower angles than in wide open angles irrespective of presence of peripheral angle synechia,19–21 and therefore it is safe to presume that smaller anterior chamber dimension may inherently pose greater aqueous outflow resistance.
ACV has many advantages over angle width parameter TISA750. First, as suggested in this study, the correlations between TISA750 in different quadrants and IOP elevation varied. This may arise from the fact that angle profile changes from median to meridian. In contrast, ACV represents the anterior chamber as a whole, making it resilient to such error. Second, we previously demonstrated that ACV was superior to angle width parameters in the differentiation of narrow angle from open angle.8 Besides, the calculation of ACV does not rely on localization of the SS, which may be time-consuming and difficult to recognize in angle synechia. Measurement of ACV requires identification of lower boundary of the cornea and upper boundary of the iris, and could be easily obtained by the built-in software.
This study has limitations. First, the duration of observation was not long enough, limiting the generalization of results to longer period of follow-up. Second, IOP >21 mm Hg at any time was treated after LPI, and OCT scans were performed at fixed time points. Therefore, we did not analyze the specific change of anterior segment structure when IOP increased. The possible mechanism of IOP rise was still unanswered.
In conclusion, the current longitudinal study proved that ACV is a reliable and accurate parameter in the evaluation of anterior segment structure and prognosis of IOP elevation after LPI. ACV better represents the volume status of anterior chamber as a whole. Although smaller ACV and TISA750 were both associated with IOP increase after LPI, TISA750 was affected by cross-sectional variation.
The authors thank Dr. XiaoJing Zhong who helped perform the LPI procedure, Dr Jun Fu and Dr Jiani Zhang who helped coordinate this project, and Dr. Guangxian Chen and Junying Zhong, who helped perform the OCT for all the enrolled patients.
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