Glaucoma••

Correlation between choroidal parameters and primary angle-closure suspect in different age groups

Abstract

Objective To investigate the correlations between choroidal parameters and primary angle-closure suspect (PACS) in different age subgroups.

Methods and analysis Participants aged 50 years or older in a rural area of Daxing District, Beijing, were recruited. Swept-source optical coherence tomography was used to measure the choroidal parameters. Demographic, ocular biometry parameters and choroidal parameters were compared between the PACS and non-PACS (NPACS) eyes. Logistic analysis was performed to explore the association between the choroidal parameters and PACS.

Results 192 (26.89%) subjects with PACS and 509 (71.29%) with PACS were analysed. Subjects were divided into two groups: group 1 (50–60 years, n=286) and group 2 (>60 years, n=415). In group 1, the mean subfoveal choroidal thickness of PACS eyes was 341.82±88.23 µm and thicker than NPACS eyes (315.07±83.53 µm, p=0.035). The choroidal volume was greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). In group 2, no significant difference in any choroidal parameters between PACS and NPACS was found. Multivariate regression demonstrated that increased choroidal volume was associated with PACS (OR 1.298, 95% CI 1.117 to 1.510, p<0.001) in group 1.

Conclusions In the age group of 50–60 years, PACS eyes had greater choroidal thickness and volume than NPACS eyes, and the increased total choroidal volume was a predisposing factor for PACS.

Trial registration number ChiCTR2000037944.

What is already known on this topic

  • The choroidal expansion plays a role in the development of angle closure. However, the alteration of choroid in primary angle closure diseases still remains controversial.

What this study adds

  • Our study showed a significant choroidal thickening in primary angle-closure suspect (PACS) eyes compared with non-PACS eyes, and the increased total choroidal volume was a predisposing factor for PACS subjects with an age of 50–60 years.

How this study might affect research, practice or policy

  • The choroidal expansion might be an important factor in the development of PACS in younger cases.

Introduction

Primary angle-closure disease (PACD) is the appositional or synechial closure of the anterior chamber angle, including a continuum of three stages: primary angle-closure suspect (PACS), primary angle-closure (PAC) and primary angle-closure glaucoma (PACG).1 2 Compared with other ethnicities, Asians have a higher risk of PACD, and the prevalence of PACD was especially high in Chinese populations.3 According to the results of Liwan Eye Study, the 10-year cumulative incidence of any form of PAC was 20.5% in South China, including 16.9%, 2.4% and 1.1% with incident PACS, PAC and PACG in either eye, respectively.4 With a higher proportion of low visual acuity and blindness, PACG was more visually debilitating compared with primary open-angle glaucoma (POAG),5 and almost half to two-thirds of the subjects with PACG were suffering from blindness in at least one eye.6–8

There has been growing interest in studying the role of the choroid in the pathophysiology of PACD. Choroidal expansion has been demonstrated in eyes with acute PACD or chronic PACD.9 10 Quigley hypothesised that expansion of choroidal volume might be a major risk factor in PACD, where choroidal expansion pushed the lens-iris diaphragm forward, initiating or aggravating a closure of the anterior chamber angle.11 However, most studies discussing PACD and choroidal thickness were hospital based, and the presence of choroidal thickening in PACS remains controversial.12 With over 1300 subjects recruited in a rural area of Beijing, we performed enhanced ophthalmic examinations including swept-source optical coherence tomography (SS-OCT), gonioscopy and ocular biometry parameters measurement in this community-based study. The choroidal parameters changes were analysed in eyes with PACS, and the correlations between choroidal parameters and PACS in different age subgroups were investigated.

Methods

Study population

The Daxing eye study is a community-based cohort study that recruited subjects aged 50 years and older in a rural area of Daxing, Beijing. The study population was made up of 1415 subjects from the baseline visit in 2018 and 1356 subjects from the follow-up visit in 2022. Without undergoing SS-OCT assessments, the baseline visits were not included in the study.

Examinations

Physical examinations included height, body weight, diastolic blood pressure (DBP), systolic blood pressure (SBP) and glycosylated haemoglobin. Body mass index was calculated as the ratio of body weight (in kilograms) divided by body height (in metres) squared. Any ocular intervention including medical treatment, cataract surgery, trabeculectomy and laser peripheral iridotomy (LPI) was documented.

All subjects underwent a comprehensive ocular examination. Only the right eye of each study participant was enrolled for further analysis. Slit-lamp biomicroscopy, gonioscopy and fundus examination were performed by two experienced ophthalmologists (SL and ML). Best-corrected visual acuity and spherical refractive error (SER) of both eyes were tested and recorded. Intraocular pressure (IOP) was measured using a noncontact tonometer (Topcon CT-80; Topcon Medical Systems, Oakland, New Jersey, USA). Ocular biometry parameters including axial length (AL), anterior chamber depth (ACD), lens thickness (LT) and central corneal thickness (CCT) were measured by Lenstar (Lenstar LS900; Haag Streit, Bern, Switzerland). The IOP and ocular biometry parameters were measured three times, and the average value was taken for statistical analysis.

Choroidal parameters including choroidal thickness, choroidal volume, choriocapillaris density and large-vessel choroidal layer density were automatically measured using SS-OCT (BM-400 K BMizar, TowardPi Medical Technology, Beijing, China), with the combination of long wavelength (1060 nm) full range swept source and 400 kHz A-scan. The 6×6 mm OCTA scan pattern, which covered a 6×6 mm rectangular area of the macular centred at the fovea, was used. The choroidal thickness was measured as the vertical distance from the Bruch’s membrane (BM) to the chorioscleral interface. The measurement of mean choroidal thickness included subfoveal choroidal thickness (SFCT), nasal choroidal thickness (NCT), temporal choroidal thickness (TCT), superior choroidal thickness (SCT) and inferior choroidal thickness (ICT). The SFCT was measured as the mean value of the central subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (central area of 1000 µm in diameter), as well as NCT, TCT, SCT and ICT corresponding to the mean values of the nasal, temporal, superior and inferior subfields of the ETDRS grid (circles between 1000 and 2000 µm). The density of the vessel layer was automatically calculated as the ratio of the pixel areas of the vessels divided by the total area of the regions. Choroidal volume was defined as the volume from the outer border of the RPE-BM complex to the choroid–sclera interface and was calculated by the built-in software. The measurements of choroidal vasculature density and choroidal volume were centred at the fovea and comprised nine subfields (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, lower, inferonasal regions) of the 6×6 mm rectangular scanning area. The total choroidal volume was defined as the sum of the choroidal volume of all nine subfields. The representative maps of choroidal parameters measured by SS-OCT are shown in figure 1.

Figure 1
Request permissionrequest permission icon
Figure 1

The representative maps of choroidal parameters measured by SS-OCT. (A) Choroidal thickness, measured as the distance between the Bruch membrane and the choroid-sclera interface. (B, C) The ETDRS grid was applied to the map, and the mean choroidal thickness was obtained for each subfield. (D) The 6×6 mm rectangular scanned area of OCTA. (E) The choroidal thickness map and nine subfields (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, lower, inferonasal regions) for choroidal vasculature density and choroidal volume measurements. (F) The map of large-vessel choroidal layer density. (G) The map of choriocapillaris density. ETDRS, Early Treatment Diabetic Retinopathy Study; ICT, inferior choroidal thickness; NCT, nasal choroidal thickness; OCTA, OCT angiography; SCT, superior choroidal thickness; SFCT, subfoveal choroidal thickness; SS-OCT, swept-source optical coherence tomography; TCT, temporal choroidal thickness.

We excluded subjects with poor OCTA image quality, glaucomatous optic neuropathy (GON), a history of acute angle closure attack and previous intraocular surgery or laser treatment. The OCT images were excluded if (1) eyes with any other ocular diseases associated with abnormal retinal or choroidal structures, such as choroidal neovascularisation, polypoidal choroidal vasculopathy, diabetic retinopathy, retinal vein occlusion, macular oedema, macular hole, epiretinal membrane and retinal detachment; (2) eyes with previous retinal photocoagulation or vitrectomy; (3) eyes with any disease that may significantly affect the quality of imaging such as opacity of cornea, cataract and vitreous haemorrhage; (4) images with algorithm segmentation failure, obvious decentration misalignment or signal index less than 7.

Diagnosis definitions

According to the International Society of Geographical and Epidemiological Ophthalmology criteria,1 PACS was defined as an eye with 180° or more in which the posterior pigmented trabecular meshwork could not be seen under static gonioscopy, with IOP<21 mm Hg and no peripheral anterior synechiae (PAS), previous acute angle closure or GON. The following conditions were identified as possible GON: a vertical cup disc ratio (VCDR) of 0.6 or greater (95th percentile of the study population), VCDR asymmetry of 0.2 or greater, optic disc haemorrhage and visible retinal nerve fibre layer defect.

Statistics

The mean and SD were used for the basic statistical description of normally distributed continuous variables while the median value and range were used to describe the continuous variables with skewed distribution. The categorical variables were described with counts and percentages. Student’s t-test or Mann-Whitney U test was applied for continuous variables, and the χ2 test was used for categorical variables. Univariate and multivariate logistic regression were performed to determine the parameters associated with PACS. In the variable selection process, all the variables whose p<0.2 along with the variables of known clinical importance were selected into the multivariate logistic regression. Multivariate logistic regression analysis was performed using the forward stepwise likelihood ratio method. Stepwise selection method with entry testing based on the significance of the score statistic, and removal testing based on the probability of a likelihood-ratio statistic based on the maximum partial likelihood estimates. The significance levels were 0.05 and 0.10 for variables entry and removal, separately. Statistical analyses were performed using the Statistical Packages for the Social Sciences (SPSS, V.27). All p values reported were two tailed, and statistical significance was considered as p<0.05.

Results

Study population

A total of 1356 subjects (2712 eyes) were examined in the present study. 583 eyes were excluded for fundus diseases or poor OCTA image quality. 26 eyes were further excluded due to the missing values of ocular biometry parameters. Among the remaining 747 eyes, 19 eye were pseudophakia, 11 subjects did not complete gonioscopy examination, 3 eyes underwent glaucoma surgery or LPI, 6 eyes were identified as GON and 7 eyes were with PAS. Therefore, a total of 192 (26.89%) eyes with PACS and 509 (71.29%) non-PACS (NPACS) were finally included.

Demographic and ocular characteristics

The demographic and ocular characteristics of the study population are displayed in online supplemental table S1. The age of the included individuals ranged from 50 to 82 years with an average of 62.62±6.27 years. Compared with the excluded group, the included subjects tended to be significantly younger (p<0.001) and had higher body height (p<0.001), lower SBP (p<0.001), lower DBP (p=0.003) and lower HbA1c (p<0.001). For ocular parameters, the included subjects had better VA (p<0.001) and shorter AL (p=0.027).

Compared with those with NPACS, individuals with PACS were older (p<0.001), had greater SER (p<0.001), shorter AL (p<0.001), shallower ACD (p<0.001) and thicker LT (p<0.001). 26.04% (50/192) of subjects in PACS group were male, compared with 34.18% (174/509) in the NPACS group (p=0.039). The characteristics and ocular biometry parameters of NPACS and PACS groups are shown in table 1.

Table 1
|
Comparison of characteristics and ocular biometry parameters between NPACS and PACS groups

Choroidal parameters in different age subgroups

All subjects were divided into two groups according to age: group 1 (50–60 years, n=286) and group 2 (>60 years, n=415). 19.58% (56/286) and 48.75% (136/415) eyes were identified as PACS in group 1 and group 2, separately. Compared with subjects in group 2, the SFCT and parafoveal choroidal thickness in all four subfields were significantly thicker in group 1 (all p<0.001). Subjects in group 1 also had an increased total choroidal volume (9.85±2.57 mm3 vs 8.73±2.77 mm3, p<0.001) and a greater large-vessel choroidal layer density (63.50%±1.81% vs 62.70%±2.81%, p<0.001). There was no significant difference in IOP, AL and ACD. The biometry and choroidal parameters are described in table 2.

Table 2
|
Comparison of ocular biometry and choroidal parameters between two age groups

Table 3 shows the choroidal parameters of PACS and NPACS eyes in two age groups. In group 1, the mean SFCT was 341.82±88.23 µm in the PACS eyes and thicker than the SFCT in the NPACS eyes (315.07±83.53 µm, p=0.035). Meanwhile, the TCT, NCT and ICT were significantly greater in the PACS eyes compared with NPACS eyes. The total choroidal volume was also greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). There was no significant difference observed in the choriocapillaris density and large-vessel choroidal layer density. In group 2, no significant difference in any choroidal parameters between eyes with PACS and PACS was found.

Table 3
|
Choroidal parameters of NPACS and PACS subjects in subgroups aged less than 60 years and over 60 years

Determinants associated with PACS

Factors associated with PACS were determined by logistic regression analysis. In group 1, multivariate regression demonstrated that the increased total choroidal volume was a predisposing factor for the presence of PACS (OR 1.298, 95% CI 1.117 to 1.510, p<0.001). Increased age (OR 1.262, 95% CI 1.080 to 1.474, p=0.003), thinner CCT (OR 0.986, 95% CI 0.975 to 0.998, p=0.026) and shallower ACD (OR 0.008, 95% CI 0.002 to 0.036, p<0.001) were also associated with PACS (table 4). In group 2, results of univariate logistic regression showed that increased age, female sex, AL, ACD and LT were potentially associated with PACS. CCT, SFCT and total choroidal volume were also included in the multivariate regression. Multivariate logistic regression demonstrated that shorter AL (OR 0.644, 95% CI 0.434 to 0.955, p=0.029) and decrease ACD (OR 0.005, 95% CI 0.001 to 0.018, p<0.001) were risk factors for PACS. The results of group 2 are shown in online supplemental table S2.

Table 4
|
Logistic regression analysis of determinants associated with PACS in the subgroup of age less than 60 years

Discussion

In this study, we used SS-OCT to investigate the choroidal parameters in NPACS and PACS eyes. To the best of our knowledge, this is the first time that SS-OCT has been used to show the choroidal parameters in PACS in an epidemiological study. Since the publication of the landmark study by Spaide et al on the visualisation of the choroid by enhanced depth imaging (EDI) in spectral-domain OCT (SD-OCT),13 the interest in the association between choroidal thickness and PACD has markedly increased. With a longer laser wavelength of 1050 nm, SS-OCT allows deeper penetration and has a faster image acquisition with more than 100 000 A-scans per second. Therefore, SS-OCT has enabled better visualising and measuring deeper ocular structures such as the choroid.14 The study of Park et al showed that SS-OCT had an advantage in detecting the posterior border of the sclera compared with SD-OCT with EDI-mode.15 Meanwhile, the automated segmental measurement software of the OCT device allowed for a more objective evaluation without bias by the manual measurements of examiners. Previously, the population-based Beijing Eye Study also investigated the SFCT in eyes with glaucoma, with a total of 3232 subjects included. SFCT was manually measured using SD-OCT with EDI modality, and results showed that the presence of angle-closure glaucoma was not significantly associated with abnormal SFCT.16 With automated measurements by the SS-OCT device, we analysed more choroidal thickness and vasculature parameters in our study, allowing an accurate and comprehensive assessment of the choroid.

Although there has been evidence that choroidal expansion is a risk factor for angle closure, the alteration of choroid in PACD still remains controversial. Contiguous with the ciliary body, the choroid is the posterior portion of the uvea and is majorly responsible for the posterior chamber pressure. This highly vascularised tissue accounts for approximately 90% of the intraocular blood flow, and the expansion of choroid regulates the volume of vitreous cavity and dynamically changes the IOP.12 By the known pressure–volume relationship of human eyes, a choroidal expansion of 50 µm can increase the IOP significantly.17 Quigley hypothesised that choroidal expansion contributed to angle closure by increasing the posterior–anterior chamber pressure differential and resulted in the iris to bow forward and close the angle.11 This theory was supported by several studies reporting that angle closure eyes had an increased choroidal thickness compared with healthy eyes. Arora’s study revealed a thicker CT in angle-closure eyes than open-angle and normal eyes.18 According to Xiulan Zhang’s study, the SFCT of all subtypes of angle closure eyes, including APAC, PACS, PAC and PACG, was thicker than healthy eyes significantly.19 However, another study by Xiulan Zhang et al showed no statistically significant difference in the posterior choroidal thickness measured by SS-OCT between PACD and normal control eyes while the anterior choroidal thickness increased in the PACD eyes,20 and the conclusion was consistence with the population-based Beijing Eye Study 2011.16 Maul et al found no difference in macular choroidal thickness between eyes with PAC/S and POAG suspect, although only 13 subjects were enrolled in the PAC/S group.21 With 192 PACS eyes involved, our results showed no difference in SFCT and choroidal volume between PACS and NPACS groups in the whole study population. However, the results of subgroup analyse suggested that the absence of the difference is likely to result from a confounding effect of age, and this finding indicated that the choroidal expansion might play a different role in the development of PACS in subjects in different age groups.

Compared those elderly patients, younger patients with PACD have some characteristics including thicker choroids, anteriorly positioned lenses, thinner and more anteriorly rotated ciliary bodies and shorter AL.20 It has been known that SFCT decreased 2–4 µm for each year of age in elderly subjects.22 23 However, some studies have found that the SFCT of individuals who are under 60 years old is not related to age,24 25 indicating a different distribution pattern of choroidal thickness in this age group. Therefore, 60 years old was set as the cut-off value for the subgroup analysis. In the present study, choroidal thickening was confirmed in subjects under 60 years old with PACS compared with subjects with NPACS. Our results also showed that the increased choroidal volume was a predisposing factor for PACS, as well as CCT and ACD, in younger subjects after adjusted for age and AL. In subjects over 60 years old, there was no correlation between PACS with both SFCT and choroidal volume. Therefore, we supposed that the choroid might have more impact on the abnormal conformation of the anterior chamber in younger patients. In eyes with a baseline short AL or narrow-angle, expansion of the choroid would likely contribute to a greater chance for angle closure, and in most cases including PACS, this process was reversible and asymptomatic. In subjects over 60 years old, with a significant thinning of choroid, this effect tended to be decreased. This mechanism also provided explanations for another phenomenon in younger PACD patients, for example, younger age was reported as a risk factor for developing malignant glaucoma after glaucoma surgery in patients with PACG.26 With significant choroid thickening and greater choroidal volume, the expansion of choroid in younger subjects should be noticed as not only a predisposing factor for PACS and other angle-closure diseases but also a risk factor in glaucoma surgery treatment.

It should be noted that the present study has a few limitations. First, in this community-based study, subjects with acute PAC were not included, and the number of PAC/PACG cases was also limited. Therefore, only subjects with PACS were involved in the analysis. Second, the diurnal variation of CT, which has been described in the previous studies,27 28 was not considered in the analysis. Since the participants in our study underwent the OCT examinations at various time of the day in a randomised manner, the bias introduced by the time of measurement was limited. Second, referred to other studies on choroidal thickness with large population,22 29 30 AL was not adjusted when we measured choroidal thickness, which has a minor effect on the magnification of OCT images and choroidal parameters. Besides, individuals with fundus diseases or poor OCT scans were excluded for the accuracy of choroidal quantification. These subjects were older than the subjects included, and the bias could not be completely excluded in the final sample, particularly in the subgroup over 60 years old. Last, this cross-sectional and observational study is a part of a community-based cohort study, and this was the first time that SS-OCT was applied for the measurement of choroid. Therefore, longitudinal follow-up is warranted to investigate the natural progression of PACS and its correlation with choroidal parameters changes in our study population.

In conclusion, our study showed a significant choroidal thickening in PACS eyes compared with NPACS eyes, and the increased total choroidal volume was a predisposing factor for PACS subjects with an age of 50–60 years. No correlation between choroidal parameters and PACS was found in subjects older than 60 years old. In younger subjects, the choroidal expansion might be an important factor in the development of PACS.

Overview

Article metrics
Altmetric data not available for this article.
Dimensionsopen-url