Analysis of Indicators for Assessing the Risk of Progression from PACS to APAC and the Degree of Intraocular Pressure Elevation in APAC Using AS-OCT

Objective The aim of this study is to quantify anterior chamber parameters to provide potential risk indicators for evaluating the progression of primary angle-closure suspect (PACS) eyes to acute primary angle closure (APAC) and the degree of intraocular pressure elevation in patients with APAC utilizing anterior segment optical coherence tomography (AS-OCT). Methods Tomey CASIA2 AS-OCT was used to quantitatively measure various anterior chamber parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), lens thickness (LT), lens vault (LV), iris-trabecular contact index (ITC), iris thickness (IT), iris volume (IV), iris curvature (IC), iris area (IA), and iris thickness (IT), in APAC eyes (30 eyes) and contralateral PACS eyes (30 eyes) of 30 patients. The differences in these parameters between the two groups and their relationship with intraocular pressure were analyzed. Results Compared to the PACS group, the APAC group exhibited significantly smaller IA and IC, and significantly larger pupil diameter (PD) and ITC (P < 0.05). There were no statistically significant differences in ACV, ACD, ACW, ACA, LV, IV, and IT750/2000 between the two groups. In APAC eyes, multivariable linear regression analysis showed a significant negative correlation between intraocular pressure and IV (β = −1.85; 95% confidence interval: −2.77 to −0.93; P=0.001), while no correlation was found in PACS eyes. In all 60 eyes, LT showed a negative correlation with ACV, ACD, ACA, and nasal IT750, and a positive correlation with LV and nasal IC. Conclusion AS-OCT has multiple advantages in evaluating various anterior chamber parameters in patients with glaucoma. IA may serve as a predictive indicator of the progression of eyes from PAC or APAC. A significant negative correlation was found between intraocular pressure and IV during APAC attacks. LT can be considered a predictive factor for the occurrence of primary angle-closure disease.


Introduction
Glaucoma is the leading cause of irreversible blindness worldwide.Primary angle-closure glaucoma (PACG) accounts for 25% of all types of glaucoma globally.It is the most common type of glaucoma in the Chinese population [1].Acute primary angle closure (APAC), classifed in the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) staging system, is a special form of primary angle-closure disease (PACD) and represents an ophthalmic emergency, characterized by the sudden closure of the anterior chamber angle leading to a rapid increase in intraocular pressure (IOP) [2].Without prompt treatment, patients may experience optic nerve damage and progressive vision loss [3].If the contralateral eye exhibits a shallow anterior chamber, narrow angle, and short axial length, even without elevated IOP, it is considered as a primary angleclosure suspect (PACS) in the ISGEO staging system [2].
In clinical practice, both ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) can be used for quantitative measurement of anterior chamber parameters [4].Compared with UBM, AS-OCT has the following advantages: noncontact, timesaving, and does not require a supine position during examination.Terefore, AS-OCT is widely used to obtain high-resolution anterior chamber images [5].It has gone through several generations of innovation, from timedomain OCT (TD-OCT), frequency-domain OCT (SD-OCT), to swept frequency OCT (SSOCT).CASIA2 SS-AS-OCT has a high scanning speed, providing higher depth sensitivity and higher resolution images.Tis makes it possible to obtain image parameter data from the cornea to the lens in just a few seconds.
In patients with PACD, if one eye presents with APAC, the contralateral eye often exhibits PACS.Terefore, it is important to assess the risk of the contralateral eye transitioning from PACS to APAC.Tis study aims to compare APAC eyes and PACS eyes in the same patient, utilizing AS-OCT quantitative measurements of anterior chamber parameters, to provide potential risk indicators for evaluating the progression of PACS to APAC in patients with PACS and the degree of IOP elevation when APAC attacks.

Study Population.
Tis study is a retrospective study conducted in accordance with the principles of the Helsinki Declaration and approved by the Ethics Committee of Shandong Lunan Eye Hospital.Te analyzed data were collected from patients with APAC who received continuous treatment in the glaucoma department of Shandong Lunan Eye Hospital from November 2022 to May 2023.A total of 30 patients (60 eyes) were included in the study, comprising 30 APAC eyes and 30 contralateral PACS eyes.Te diagnosis of APAC and PACS was based on the diagnostic criteria of the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) [6].All study participants were over 60 years old and had mild cataracts.Te exclusion criteria were as follows: (1) patients with simultaneous acute attacks in both the eyes; (2) patients with a history of recurrent minor attacks and obvious optic nerve damage; (3) patients who had previously undergone any laser or intraocular surgery (including LPI, laser iridoplasty, trabeculectomy, and other glaucoma-related treatments, as well as any other intraocular surgery); (4) patients with known eye diseases that afect the anterior chamber anatomy, such as ciliary or iris cysts, a history of trauma, and the use of medications that afect iris confguration; (5) patients with a history of any other intraocular diseases or concurrent intraocular diseases, such as uveitis, diabetic retinopathy, macular degeneration, or retinitis pigmentosa; and (6) patients with life-threatening or systemic diseases that may afect the study results.

AS-OCT Image Acquisition and Parameter
Measurements.AS-OCT imaging was obtained before the initiation of acute attack treatment by the same experienced ophthalmic technician.All patients underwent AS-OCT examination in a dark room environment using the Tomey CASIA2 device (Tomey Corporation, Nagoya, Japan).CASIA2 utilized a 1310-nm swept-source laser wavelength with a frequency of 0.3 s.Continuous scanning was performed in the "anterior chamber angle" mode.Images were obtained and analyzed using the provided software by the manufacturer.Te anterior segment structures were automatically analyzed by the built-in software and the measurement results were provided after marking the scleral spur (SS).SS was defned as the point of curvature change at the junction of the cornea and sclera, where the sclera protrudes inward.A trained technician marked the SS without knowledge of the anterior chamber angle grading.Te analyzed parameters included iris-trabecular contact index (ITCI, defned as the percentage of iris-trabecular contact area to the total measured area), anterior chamber volume (ACV), anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber area (ACA), lens vault (LV, defned as the distance between the intersection of the vertical bisector of SS connection and lens and the midpoint of SS connection), lens thickness (LT), iris area (IA), iris volume (IV), iris curvature (IC), and iris thickness at 750/2000 μm (IT750/2000).

Management of Acute Angle-Closure Glaucoma Attacks.
A standard protocol was followed for the management of acute angle-closure glaucoma (AAC) attacks.Initially, local and systemic medications were used to alleviate the attack.If the symptoms did not subside after 2 hours of medication, laser peripheral iridoplasty (LPIP, energy: 300-340 mW, spot size: 500 μm, exposure time: 700 ms) was performed.If the symptoms still persisted and corneal edema was severe, leading to the lens extraction surgery being unfeasible, a low-dose transscleral cyclophotocoagulation (TSCPC) was further conducted to reduce IOP.All patients underwent ultrasound phacoemulsifcation combined with gonioscopy-assisted goniosynechialysis, under good corneal transparency and controlled intraocular infammatory.Te surgeries were performed by an experienced glaucoma specialist under topical anesthesia.

Statistical Description.
Statistical analysis was performed using the Free Statistics software version 1.7.1.Categorical variables were described as frequencies (%), while continuous variables were described as mean-± standard deviation (SD) or median (range), if the data were not normally distributed.Te paired t-test was applied for the parameters within APAC and PACS groups in Tables 1 and 2. Multivariable linear regression models were employed to explore correlations between the various parameters.A P value less than 0.05 was considered statistically signifcant.

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Journal of Ophthalmology   5 and Figure 1).Among the abovementioned parameters, only the     Journal of Ophthalmology relationship between LT and IT750 has not been reported previously; hence, we further adopted stratifed analysis to assess whether the correlation of LT with IT750 was robust in diferent subgroups (Figure 2).Te subgroup analyses were performed using diferent stratifed logistic regression models according to sex, diagnosis, BMI, hypertension, and diabetes.No signifcant interaction was observed in all fve subgroups (all P > 0.05).

Discussion
Over the years, known risk factors for APAC, such as shallow anterior chamber, narrow peripheral angles, thicker lens, anterior lens position, and shorter axial length, have been identifed using ultrasound biomicroscopy, gonioscopy, and A-scan biometry.Although these traditional tools have helped us understand the basic pathogenesis of APAC, they have limitations such as being invasive, nonautomated, subjective, time-consuming, and nonquantitative.AS-OCT has gained popularity due to its advantages of upright positioning, noncontact measurement, rapidity, semiautomation, objectivity, high resolution, quantifcation, and high repeatability [7,8].In this study, Tomey CASIA2 AS-OCT was used to assess the diferences in anterior segment parameters between APAC and PACS within Chinese patients.Compared to previous AS-OCT devices, CASIA2 ofers advantages such as faster scanning speed and built-in programs, allowing for the measurement of average anterior chamber parameters in 360 °within seconds.It is widely utilized for anterior segment evaluation in patients with PAC disease [9].Tis study found that, compared to the PACS group, the APAC group had larger pupil diameter (PD) and smaller iris area (IA) and iris curvature (IC).Tis fnding aligns with previous research that discovered an interesting phenomenon: for each 1 mm increase in PD in PACG eyes, there is a loss of 0.145 mm 2 in IA in the same eye and a loss of 0.161 mm 2 in the fellow eye.In normal control eyes, the loss is 0.165 mm 2 [10].In other words, in APAC eyes, due to the dilation of the pupil, there is a corresponding loss in IA, which is consistent with the fndings of our study.Combining previous research with our results indicates that when comparing PACS eyes to PACG eyes with the same increase in PD diameter, PACG eyes have a smaller loss in IA.Tis suggests that in clinical practice, during AS-OCT examination under darkroom conditions for patients with PACS without a history of acute attacks in both eyes, a larger IA may indicate a smaller loss in IA, making the eye more prone to developing PAC or PACG.Terefore, IA could potentially serve as a predictive indicator for the progression from PACS to PAC or PACG.In addition, our study also found a negative correlation between IOP and iris volume (IV) during acute attacks in APAC eyes, while there was no correlation between IOP and IV in the PACS group.Tis phenomenon was explainable.IV may be reduced as IOP increases as a result of IOP-related iris compression or anterior segment ischemia.Tis study also found a decrease in IC in the APAC group compared to that in the PACS group.Tis could be attributed to the acute increase in IOP during an acute angle-closure attack, which leads to angle closure, obstruction of aqueous outfow, and increased pressure in both the anterior and posterior chambers, thereby resulting in a reduction in IC.However, Guzman et al. conducted a clinical-based study in Singapore, specifcally focusing on patients with PACD of Chinese ethnicity, and found no signifcant diferences in IA and IC between PACS and PAC/PACG eyes [11].Tis discrepancy may be attributed to the diferences in the study population.Our study primarily focused on APAC eyes, which represent a distinct subtype of PACG, characterized by a rapid increase in IOP and pupil dilation, thereby leading to changes in iris parameters.Tis discrepancy between our study and the study by Guzman et al. highlights the need for studies with larger sample sizes to further validate these fndings.
Lens thickness (LT) is negatively correlated with anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber area (ACA), while it is positively correlated with lens vault (LV) and IC.Saxena et al. also found that an increase of 0.01 mm in LT was associated with an 11% increase in the occurrence of ACG [12], which aligns with our study's fndings.A thicker lens implies a larger LV, and several population-based studies have demonstrated that a thicker and more anteriorly positioned lens can predict angle closure [13].LT has been reported as a predictive factor for PACD, with a larger LT indicating a greater curvature of the anterior surface of the lens with aging, thereby increasing the likelihood of pupillary block, which is considered a key element in PACD [14,15].Tis also confrms the role of the lens in anterior chamber crowding and pupillary block.Some studies have reported that a larger iris curvature is associated with a greater increase in anterior chamber angle width after LPI, which can be attributed to the relief of the pupillary block and subsequent widening of the angle.Tis provides further evidence that when LT is larger, IC is larger, and the pupillary block is more pronounced, thus resulting in a shallower anterior chamber.Conversely, when LT is smaller, IC is smaller, indicating a fatter iris, and the anterior chamber is deeper [16,17].
However, this study also has certain limitations.First, the sample size was small, and further research with a larger number of participants is needed.Second, although we usually perform AS-OCT at the time of patient admission, some patients may have already been treated with IOPlowering drugs in other hospitals, which may afect certain parameters.Lastly, this study primarily focused on the preoperative parameters of the two groups, and it would be benefcial to supplement this research by examining parameter changes at various postoperative time points through regular follow-ups.

Conclusions
AS-OCT ofers several advantages in assessing various parameters of the anterior segment in patients with glaucoma.IA may serve as a predictive indicator for the progression from PACS to PAC or APAC.A signifcant negative correlation was found between IOP and IV during APAC attacks.LT can be considered a predictive factor for the occurrence of PACD, in which pupillary block is a key contributing factor.

Figure 1 :
Figure 1: Linear regression analysis of the correlation between lens thickness (LT) and various indicators in all 60 eyes (adjusted for age, BMI, gender, diagnosis, hypertension, and diabetes).

Figure 2 :
Figure 2: Association between lens thickness (LT) and nasal iris thickness at 750 μm (IT750) according to baseline characteristics.Model I: adjusted for age, BMI, and gender.Model II: adjusted for the variables in model I plus diagnosis, hypertension, and diabetes.

Table 1 :
Demographics and characteristics of participants.

Table 2 :
Comparison of AS-OCT parameters between the APAC group and the PACS group.

Table 3 :
Linear regression analysis of the association between initial IV and IOP in the APAC group.I: adjusted for age, BMI, and gender.Model II: adjusted for the variables in model I plus hypertension and diabetes. Model

Table 4 :
Linear regression analysis of the association between IOP and IV in PACS group.I: adjusted for age, BMI, and gender.Model II: adjusted for the variables in model I plus hypertension and diabetes. Model

Table 5 :
Linear regression analysis of correlation between LT and various indicators in all 60 eyes.
Model I: adjusted for age, BMI, and gender.Model II: adjusted for the variables in model I plus diagnosis, hypertension, and diabetes.