Corresponding Author: Kyung Rim Sung, MD, PhD. Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Glaucoma is a major cause of irreversible blindness worldwide [1,2]. Primary angle-closure glaucoma (PACG) is associated with greater visual morbidity and higher rates of blindness compared with primary open-angle glaucoma, particularly in Asian populations [3,4]. Current definitions of PAC disease (PACD) are based on the presence of iridotrabecular contact (ITC) by gonioscopic examination [5]. PACG, characterized by a glaucomatous optic disc or visual field (VF) impairment along with the presence of ITC, is the most advanced stage of PACD. Furthermore, PACD spectrum includes PAC suspects (PACS) and PAC, which has no glaucomatous structural and/or functional damage [5].
Swept-source (SS) anterior-segment optical coherence tomography (AS-OCT) can evaluate the anterior chamber angle (ACA) configuration and provide quantitative and repeatable parameters including ITC by obtaining cross-sectional imaging of the anterior segment using a noncontact method [6,7].
Although numerous treatment options exist, such as intraocular pressure (IOP)-lowering medications, laser peripheral iridotomy, and argon laser peripheral iridoplasty, lens extraction is regarded as the most definitive treatment modality for resolving angle closure [8,9]. Because PACD is a spectrum of diseases, the characteristics of PACD in terms of angle status or IOP control before and after lens extraction may vary depending on the specific disease of the patient [9,10]. PACG has a tendency to deteriorate rapidly and frequently has a worse response to medical treatment compared with primary open-angle glaucoma; thus, close monitoring of IOP and aggressive management are required [10]. Therefore, we compared the changes in the SS AS-OCT parameters and IOP control after lens extraction in PACD spectrum between eyes with the presence of optic disc/VF damage (i.e., PACG) and those without damage (i.e., PACS + PAC).
Materials and Methods
Ethics statement
This study was approved by the Institutional Review Board of Asan Medical Center (No. 2022-1200), with a waiver of informed consent due to the retrospective nature of the study. The study adhered to the tenets of the Declaration of Helsinki.
Patients
This retrospective, clinical cohort study enrolled consecutive patients who underwent lens extraction by a single surgeon with uneventful phacoemulsification and intraocular lens implantation, from August 2021 to June 2022, among those who were diagnosed with PACD at the glaucoma clinic of the Asan Medical Center (Seoul, Korea). All subjects underwent a complete ophthalmic examination including slit-lamp examination, gonioscopy, fundoscopy, best-corrected visual acuity (BCVA) measurement, Goldmann applanation tonometry, retinal nerve fiber layer photography (Auto Fundus Camera AFC-330, Nidek), stereoscopic optic disc photography (Canon), VF test (Humphrey field analyzer; Swedish Interactive Threshold Algorithm 24-2, Carl Zeiss Meditec), spectral-domain OCT (Cirrus HD-OCT, Carl Zeiss Meditec), axial length measurement (IOLMaster 700, Carl Zeiss Meditec), and SS AS-OCT (CASIA 2, Tomey). Only patients who had completed at least 6 months of follow-up examinations after surgery were included in the analysis. If both eyes were applicable, one eye was chosen randomly and included in the analysis.
Participants were classified according to the following criteria. PACS was classified as eyes with a narrow angle, peripheral angle closure of at least 180° on static gonioscopic examination with normal IOP and absence of optic disc damage or peripheral anterior synechiae (PAS) [11]. Eyes with PAC exhibited occludable angles and gonioscopic evidence of trabecular obstruction by the peripheral iris such as elevated IOP or PAS without glaucomatous VF or optic disc changes [11]. Eyes diagnosed with PACG had anterior chamber features of PAC and were accompanied by glaucomatous optic disc changes (disc excavation, neuroretinal rim thinning, and/or optic disc hemorrhage attributable to glaucoma) and/or VF changes suggestive of glaucoma [11]. All patients were divided into two groups: PACS and PAC patients in group A and PACG patients in group B.
Patients who had a history of laser peripheral iridotomy or argon laser peripheral iridoplasty, topical or systemic medications that could affect the pupillary reflex, or ACA prior to lens extraction were excluded from the study. Those who had lens extraction combined with a glaucoma drainage device or filtering surgery were also excluded from the study. Eyes with secondary causes of angle closure, including uveitic and neovascular glaucoma, were also excluded [5,12].
IOP measurements were taken 2 weeks to 1 month before surgery and at 1 day, 1 week, and 1, 3, and 6 months after the lens extraction. As a representative postoperative IOP value, the IOP measured at 1 month after surgery was analyzed. The degree of IOP reduction after surgery was defined as the percentage difference between preoperative and 1-month postoperative IOP. Postoperative IOP fluctuations were determined as the difference between the highest and lowest IOP values measured during 6 months after surgery.
SS AS-OCT
SS AS-OCT images from all subjects were obtained before and at 1 month after lens extraction. An independent, qualified, single inspector (WKS) assessed all AS-OCT images. Scanned images with good central fixation, great scleral spur resolution, and absence of motion artifacts were chosen for data processing. If the location of the scleral spur was unclear due to PAS or other causes, consultation was conducted with another co-inspector, and only cases where the two inspectors agreed on the location of the scleral spur were included in the analysis. Poor-quality images including cases where the locations of the scleral spur were different between two inspectors, were excluded from the analysis. The examiner evaluated all images blinded to the patients’ clinical information and the results of other examinations.
Four meridional scans cross-sectioned at 0°-180°, 45°- 225°, 90°-270°, and 135°-315° were conducted around the ACA circumference for each eye, and for each scan the parameters specified in the manufacturer’s software were measured [6,7]. These parameters included the mean anterior chamber area, anterior chamber depth (ACD), lens vault, anterior chamber volume, and angle opening distance (AOD) and trabecular-iris space area (TISA) at 500 and 750 μm from the scleral spur. Fig. 1A-1D shows each parameter schematically. The anterior chamber width was measured as the distance between both scleral spurs on either side at each meridional scan. The ITC index and area were defined as the percentage of the circumference and the total area where there was contact between the iris and the inner surface of the cornea in the anterior part of the scleral spur. The ITC index and area were computed using 360° circumferential scans with semiautomated software. To assess the change in the ITC index before and after surgery, the ratio of the decreased ITC index value after surgery to the preoperative ITC index was represented as a percentage. Except for the ITC index and area, representative values of all other preoperative and postoperative ACA parameters were determined by averaging four meridional AS-OCT scans.
Statistical analysis
Statistical analyses were performed using IBM SPSS ver. 23.0 (IBM Corp). Baseline demographics, ocular characteristics, and preoperative and postoperative SS AS-OCT parameters were compared between subgroups in the different spectrum of PACD using either t-test or Mann-Whitney U-test depending on the normality of distribution. Correlations between SS AS-OCT parameters and perioperative IOP reduction (%) were evaluated by univariate and multivariate linear regression analyses. Parameters that showed p < 0.05 in univariate analysis were categorized into preoperative, postoperative, and amount of change values, and multivariate regression analysis was performed for each category.
Results
Baseline demographics and ocular characteristics
Among 101 eyes from 101 patients that met the initial inclusion criteria, nine (8.9%) were excluded from the analysis due to poor SS AS-OCT image quality. Finally, 92 eyes were included in the analysis, of which 50 eyes were in group A (PACS + PAC) and 42 eyes were in group B (PACG).
Table 1 shows the baseline characteristics of the two groups. Group A had significantly longer axial length and fewer numbers of preoperative glaucoma medications than group B. In both groups, the number of glaucoma medications (0.56 ± 1.01 vs. 2.00 ± 0.91, p < 0.001) was reduced to less than half after lens extraction, but group B required more glaucoma medications (0.18 ± 0.66 vs. 0.88 ± 0.80, p < 0.001) and had a lower BCVA than group A. Preoperative and postoperative IOP measurements are shown in Table 2 and Fig. 2. There were no significant differences in IOP measurements at each visit between the two groups, including IOP fluctuation and percentage IOP reduction after lens extraction.
Comparison of SS AS-OCT parameters between two groups
Comparison of the SS AS-OCT parameters and differences in parameters between two groups before and after lens extraction are shown in Table 3. Before lens extraction, the SS AS-OCT parameters were comparable between the two groups, with the exception of anterior chamber width. AOD and trabecular-iris angle at 750 μm were significantly greater in group B at the postoperative assessment, whereas other parameters did not differ significantly. Group B demonstrated a greater change in AOD at 500 and 750 μm and TISA at 750 μm after lens extraction than group A. Table 4 shows changes in ITC-related parameters after lens extraction. The ITC index and area were decreased significantly in both groups after surgery. There was no significant difference between the two groups in preoperative ITC index, area, or location. However, the residual ITC index and area were greater and the degree of postoperative ITC reduction (%) was lower in group B. In terms of location, the ITC index did not differ between the two groups in all four quadrants preoperatively; however, the ITC index was significantly greater in group B in the inferonasal quadrant at the postoperative assessment.
Relationship between postoperative IOP reduction and SS AS-OCT parameters
Table 5 shows the results of regression analysis to identify the factors influencing IOP reduction after surgery in PACD. In terms of postoperative IOP change (%) as a dependent variable, multivariate linear regression analysis was performed with statistically significant factors in the univariate analysis. The results showed that the parameters related to the degree of IOP reduction were preoperative IOP, and the amount of ITC index change after surgery, greater preoperative IOP, and ITC index change were associated with a greater degree of IOP reduction overall. A similar trend was seen when analyzed separately into groups A and B. Tables 6 and 7 show the results of the regression analysis of factors affecting the degree of IOP reduction after surgery in groups A and B, respectively. In groups A and B, a smaller postoperative ITC index and larger ITC index change were associated with a greater degree of IOP reduction after surgery.
Discussion
Previous studies have reported that lens extraction in PACD is effective at controlling IOP and subsequently improving the prognosis [13-15]. However, other studies have shown that PACG had a worse prognosis than PAC and PACS, even after lens extraction, and preoperative retinal nerve fiber layer thinning and postoperative IOP fluctuation were associated with functional glaucomatous progression after surgery [8,10]. The present study was conducted to analyze and compare the changes in SS AS-OCT and IOP-related parameters before and after lens extraction depending on the presence of glaucomatous function or structural damage within the PACD spectrum and to identify which factors affected the IOP control in each group.
Baseline demographics showed no significant difference in sex, age, and central corneal thickness between the two groups. However, group B had a shorter axial length compared to group A, which was different from a previous study [16]. However, short axial length is a risk factor for angle closure, which may affect the progression of PACS/ PAC to PACG [17]. Before and after lens extraction, group B used a greater number of glaucoma medications. This could be interpreted as being caused by the presence of glaucomatous optic nerve damage in this group. However, in both groups, there was a significant reduction in the number of glaucoma medications after surgery, confirming that lens extraction is an important treatment strategy for resolving angle closure and lowering IOP. Furthermore, there was no significant difference in the IOP before and after surgery between the two groups. This lack of a significant difference may be attributed to the different number of glaucoma medications used in the two groups, with the PACG group using more medications. Consequently, a direct comparison of the IOP between the two groups may be challenging due to this difference in medication usage.
In contrast to the IOP, which can be influenced by glaucoma medications, a quantitative analysis of SS AS-OCT showed meaningful differences between the two groups. Before surgery, angle parameters were not significantly different between the two groups. However, after surgery, AOD and trabecular-iris angle at 750 μm were larger in group B. When comparing the changes after surgery, the differences between the two groups were more pronounced. Although no study has directly compared angle changes before and after cataract surgery between PACD subgroups, a study measuring perioperative ACD changes in PACD suggested that while statistical significance may not be strong, the PACG group tended to have larger ACD changes before and after surgery. Even within the PACG group, those in advanced stages tended to have a wider ACD after cataract surgery [18]. A possible explanation could be that as PACD progress over time, zonules may loosen, causing the intraocular lens to be positioned further posteriorly after surgery, which might lead to a deeper ACD and wider angle in advanced PACD after surgery. To verify this hypothesis, future studies should investigate the position of the intraocular lens.
In this study, we conducted a detailed analysis of the perioperative angle parameters across different PACD spectrum subgroups. After surgery, the anterior angle of PACG eyes became significantly wider, but the residual ITC index and area remained higher, and the ITC reduction percentage was relatively small, compared with group A. In the regression analysis, which identified factors inf luencing the degree of IOP reduction after surgery for each of the two groups, the smaller the residual ITC index after surgery and the larger the change in ITC index after surgery, the lower the IOP after surgery, rather than the other ACA parameters in both groups.
Therefore, in PACD patients, the degree of ITC and residual trabecular function are very important in determining postoperative IOP control. A previous large-scale study revealed that the ITC and IOP had a positive correlation in the range of ITC index over 63% or ITC area exceeding 8.8 mm2 [19]. It was found that the average postoperative ITC index in PACG was 10.68% ± 12.10%. Although this value alone may not lead to significant IOP elevation, considering that the cause of residual ITC is likely synechial closure, it can be assumed that the higher postoperative ITC index in group B ref lects compromised trabecular function compared with group A.
This compromised trabecular function in the PACG group may explain why IOP control remains more challenging after surgery in the PACG group, which has more rapid glaucoma progression than PACS/ PAC af ter phacoemulsification [9]. Therefore, lens extraction of PACS/PAC eyes before the progression to PACG, before synechial closure occurs, is crucial for resolving angle closure and preventing future glaucoma progression.
This study had several limitations. First, due to its retrospective study design, it is challenging to have a uniform indication for lens extraction and criteria for patient inclusion and IOP control. Second, the PAC group only contained 14 individuals, which might be too small to subdivide further according to the definition of the PACD spectrum. Due to the small sample size, we conducted the study by dividing individuals into two groups based on the presence of glaucomatous optic neuropathy or functional damage. Third, the differences in the number of glaucoma medications between the groups made it difficult to directly assess the effect of lens extraction on the IOP in each group. Additionally, we were unable to obtain results matched for the mechanisms of angle closure because of the complicated study design. This should be performed in a future study. Finally, since anterior segment and chamber angle structures are closely located, such parameters driven by AS-OCT are correlated and subsequently our multivariate analysis can be affected by multicoliearity. This should be considered when interpreting the result. Due to these limitations, larger-scale, prospective studies with more standardized criteria for patient inclusion and management to draw more definitive conclusions about the relationship between lens extraction, angle closure, and IOP control in the context of PACD are needed.
In conclusion, the PACS/PAC group did not show a difference in postoperative IOP compared with the PACG group, but there was a clear difference in the number of glaucoma medications used, with more being used in the PACG group. The residual ITC index was higher in the PACG group, which was suspected to be related to synechial closure and compromised trabecular function. Therefore, performing lens extraction at an appropriate time before progressing to chronic angle closure and synechial change, or glaucomatous optic neuropathy, appears to be crucial for long-term prognosis in PACD spectrum.
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