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BMC Ophthalmology logoLink to BMC Ophthalmology
. 2026 Jul 4;26:605. doi: 10.1186/s12886-026-05059-2

Longitudinal changes in vessel density and retinal nerve fiber layer thickness after acute primary angle closure

Qian Hao 1,2,#, Yuan Qin 4,#, Linwei Yan 5, Yue Wang 1, Ju Li 1,3, Fang Fan 1,✉
PMCID: PMC13625481  PMID: 42401889

Abstract

Objective

To evaluate the initial and longitudinal alterations of peripapillary optic disc vessel index in eyes with a history of acute primary angle closure (APAC) and to explore the better predictor of glaucoma progression.

Methods

Twenty-one consecutive Chinese patients who were successfully treated for a unilateral episode of APAC were included in the study. The observation group consisted of eyes with the history of acute episode, while the contralateral eyes without an attack served as the control group. All APAC eyes underwent phacoemulsification cataract extraction, intraocular lens implantation and goniosynechialysis one day after the remission of episode. Moreover, the contralateral eyes were performed laser peripheral iridotomy (LPI). Patients were followed-up at 1 day after remission of APAC and 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. All participants underwent ophthalmic examinations after remission of the acute episode but before surgery, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), axial length (AL), visual field (VF), and retinal nerve fiber layer (RNFL) thickness and circumpapillary vessel density (cpVD) obtained by swept-source optical coherence tomography(SS-OCT). Correlation analysis was performed to identify the cpVD as a predictor of glaucoma progression.

Results

The vascular network was visibly attenuated and focal capillary dropout was evident in APAC eyes. The cpVD 1 day after APAC episode and 1 week postsurgery in APAC eyes was 45.96% (45.96 ± 3.41), and 46.19% (46.19 ± 3.15) which were significantly (P=0.020 and P༝0.035) reduced compared to 48.35% in the unaffected eyes. However, it remained stable during the follow-up in the subsequent year. The retinal nerve fiber layer (RNFL) thickness initially showed thickening at 1 day (P༝0.05), and followed by a progressive thinning from 1 week (P༝0.04) to 6 months (P༝0.02), and eventually reached a stable state. At the last follow-up in APAC eyes, peripapillary retinal VD was positively correlated with RNFL thickness (P༝0.01) and negatively correlated with VF mean deviation (P༝0.04).

Conclusion

In APAC eyes, the circumpapillary VD decreased significantly 1 day after the APAC episode was fully resolved, and remained stable during the follow-up. However, the RNFL thickness ultimately plateaued at a stable level at 6 months. Thus, cpVD may be the more sensitive predictor than the RNFL thickness for the glaucomatous progression of APAC patients.

Clinical trial registration number if required

Not applicable.

Keywords: Acute primary angle closure, Circumpapillary vessel density, Retinal nerve fiber layer, Visual field

Highlights/Key messages

•What is known:

• The previous studies demonstrate that an initial increase in RNFL thickness after a single APAC episode, followed by a subsequent decrease.

• The high IOP has a greater impact on the changes in vessel density parameters after an APAC episode.

•What is new:

• The study demonstrates that the cpVD decreased significantly 1 day after the APAC episode was fully resolved, and remained stable during the follow-up.

• The study demonstrates that the cpVD was the more sensitive predictor than the RNFL thickness for the glaucomatous progression of APAC patients.

Introduction

Glaucoma, characterized by distinctive optic nerve atrophy and visual field defects, stands as the leading cause of irreversible blindness globally. It is projected that the number of individuals affected by glaucoma will increase to 111.4 million by 2040 [1]. With the demographic shift towards an aging population in China, literature estimated that the number of glaucoma-induced blindness cases reached 5.67 million by 2020 [2]. Among these, Primary Angle Closure glaucoma (PACG) is the most prevalent form in China [3], and APAC is the most common type, with blindness rates ranging from 6% to 32.4% [4]. The exact mechanism of optic neuropathy in APAC remains incompletely understood [5]. It is currently believed that the principal mechanisms underlying glaucomatous optic neuropathy and vision loss are mechanical compression and vascular insufficiency [6]. While mechanical compression is widely accepted as the primary mechanism in APAC, previous studies have paid scarce attention to vascular factors [7].

Recent studies show that alterations in retinal and choroidal blood flow in APAC have garnered increasing attention from scholars both domestically and internationally [8, 9]. Importantly, APAC requires earlier and more sensitive diagnostic and prognostic biomarkers [10]. Therefore, investigating early fundus vascular factors is crucial. However, longitudinal changes in circumpapillary vessel density and RNFL thickness following remission of APAC are not well described. Moreover, no studies have attented that the change of cpVD 1 day after an episode of APAC, and the trajectory of cpVD within 1 year follow-up period. In addition, there is scarce research on the specific time for establishing RNFL thickness as a valid evaluative parameter. Thus, optical coherence tomography angiography (OCTA) which enables noninvasive, depth-resolved retinal imaging with a wide scan area and minimal motion artifacts can be utilized to quantify circumpapillary vascular biomarkers [11, 12]. Understanding the morphological characteristics of optic disc blood flow and microstructure in APAC, along with their long-term VF, holds significant clinical implications for early diagnosis and prognostic evaluation in APAC patients.

The current study aimed to observe changes in the RNFL thickness and cpVD over 1 year after a treated APAC episode, utilizing SS-OCT and SS-OCTA. It seeks to explore the correlation between optic disc blood flow indicators, structural indicators, and visual fields. The objective was to utilize long-term, frequent follow-up intervals to investigate the stabilization timelines of cpVD and RNFL thickness, and to identify biological indicators of significant clinical value for early prognostic evaluation and long-term follow-up in APAC.

Methods

Patients

This was a prospective study. Twenty-one patients with unilateral APAC, who visited the ophthalmology department of Hebei Provincial People’s Hospital from October 2022 to March 2024 were enrolled. The study had the approval of the Ethics Committee of Hebei General Hospital (review approval of the Ethics Committee of Hebei General Hospital: (2025) Research Ethics No. (072)). All patients provided written informed consent.

The following criteria were used to define cases of APAC: (1) presence of at least 2 of the following symptoms: ocular and periocular pain, headache, nausea, vomiting, blurred vision; (2) presence of all the following signs: conjunctival congestion, corneal epithelial edema, mid-dilated unreactive pupil, shallow anterior chamber; (3) IOP at presentation of 30mmHg or more (as measured by Goldmann applanation tonometry) (4) narrow angles in at least two quadrants on gonioscopic examination (defined as invisible posterior trabecular meshwork in at most 180 degrees with gonioscopy).

The inclusion criteria were as follows: (1) unilateral APAC and the other eye was unaffected; (2) remission after acute episode and IOP control (<21 mmHg); (3) meet the diagnostic criteria for cataract.

The exclusion criteria were as follows: (1) history of previous APAC in the affected or contralateral eyes; (2) secondary angle closure, such as lens induced glaucoma, neovascular glaucoma or uveitic glaucoma (3) history of intraocular laser therapy or intraocular surgery in the affected or contralateral eyes; (4) evidence of any retinal disease; (5) poor quality OCTA or OCT scan of the optic disk (i.e., signal strength index<45, motion artefact, poor segmentation, poor clarity).

All APAC eyes underwent phacoemulsification cataract extraction, intraocular lens implantation and goniosynechialysis one day after the remission of episode. Before the start of surgery, all patients received topical anesthesia with proparacaine hydrochloride eye drops. Moreover, the contralateral eyes were performed laser peripheral iridotomy (LPI). All patients were followed up at the following time points after the APAC episode: 1 day after remission and 1 week, 1 month, 3 months, 6 months, and 1 year after surgery.

Examinations

All patients enrolled underwent thorough ophthalmic examinations including best-corrected visual acuity (BCVA), slit-lamp examination, fundus examination. IOP was measured by Goldmann applanation tonometry (GAT, Keeler, UK). axial length (AL) was measured by Intraocular lens Master (IOL Master, ZEISS, Germany). Gonioscopy was performed with a single-mirror gonioscope (OSMG, Ocular, USA). Visual field examinations were performed with the Humphrey Field Analyzer (ZEISS, Germany). UBM (SW-3200 L, China) was utilized to assess the condition of angle adhesion. The RNFL thickness and cpVD were assessed with swept-source optical coherence tomography (SS-OCT, Topcon, Japan).

Optical coherence tomography data acquisition and processing

OCTA was performed on all participants by a single experienced technician. The scans were obtained using the Angio mode of the SS-OCT system with IMAGEnet6 software. A 4.5 × 4.5 mm scan centered on the optic disc was performed to assess retinal microvasculature. Three images were captured for each eye, and the image with the highest signal quality was selected for analysis. Image analysis was conducted using the built-in IMAGEnet6 software, with manual adjustment of the segmentation layer to the inner plexiform layer-retinal ganglion cell (IPL-RGC) complex. The system automatically divided the peripapillary area into superior, inferior, nasal, and temporal sectors, calculating the cpVD for each sector, which were then recorded.

Statistical analysis

Data organization and statistical analysis were performed using Excel and SPSS 26.0 software. Normality of all continuous variables was assessed using the Shapiro-Wilk test. Data following a normal distribution were presented as mean ± standard deviation (SD), while non-normal distribution were shown as medians. Comparisons between two groups were compared using the Paired samples t-test or Wilcoxon signed-rank test, depending on data distribution. The vessel density and RNFL thickness parameters were compared in APAC eyes at each time-point using Repeated measure ANOVA. If homogeneity of variance was assumed, Bonferroni test was applied; otherwise, the Friedman test was used for non-parametric comparisons. The relationships between the cpVD, RNFL thickness and VF index were evaluated using Pearson or Spearman rank correlation. Pearson correlation was used to evaluate single correlations between normally distributed variables. Spearman rank correlation test was used to evaluate single correlations between variables with non-normal distributions. A significance level of α = 0.05 was set, and a P-value < 0.05 was considered statistically significant.

Results

Baseline clinical characteristics

Out of 30 patients, 9 were excluded because of loss of follow-up (2 cases) or poor OCTA quality (4 cases) or IOP increase once more(3 cases). Thus, 21 patients with unilateral APAC were included in the analysis (Table 1). Seventeen were female and 4 were male, with a mean age of 66 years (range, 58–74 years). Among APAC eyes, all had undergone phacoemulsification surgery, intraocular lens (IOL) implantation and goniosynechialysis (GSL) at 1 day after remission. The contralateral eyes of APAC patients received laser peripheral iridotomy (LPI) by the same surgeon. There were significant differences in IOP at presentation and BCVA (all P < 0.001, Table 1) between APAC eyes and contralateral group eyes. There was no significant difference in AL between APAC eyes and contralateral eyes. IOP measurements were always performed prior to OCTA acquisition. No significant changes in IOP were observed during the follow-up period (P = 0.73 Table 2). The mean deviation (MD) of visual field testing at 1 year was lower in APAC eyes than in control group eyes (P = 0.003 Table 1). The affected eyes had a thinner RNFL thickness(P=0.02 Table 1), when compared with the contralateral eyes at 1 year.

Table 1.

Comparison of clinical and ocular characteristics of eyes with APAC and their contralateral eyes

Variable APAC eyes
(N = 21)
contralateral eyes
(N = 21)
P Value
Sex(F/M) 17/4 -
Age(year) 66 ± 8.03 -
AL (mm) 22.23 ± 0.96 22.35 ± 0.79 0.282*
BCVA 0.18(0.1, 0.3) 0(0, 0.1) <0.001†
IOP at presentation (mmHg) 44(37, 49.5) 19(17, 21) <0.001†
VF MD (dB) at 1 year -6.7(-11.83, -5.01) -4.23(-5.48, -2.98) 0.003†
Average RNFL at 1 year 81.00(67.00, 93.38) 104.75(93.75, 113.63) 0.02†

AL=axial length; BCVA=best-corrected visual acuity; IOP=intraocular pressure; VF MD=visual field mean deviation; RNFL=retinal nerve fiber layer; APAC=acute primary angle closure

* A paired t-test and † Mann-Whitney U test were applied

Table 2.

The changes of IOP(mmHg) in the observation group over time

1 day 1 week 1 month 3 months 6 months 1 year PValUe
IOP(mmHg) 16.24 ± 3.02 16.05 ± 2.54 15.86 ± 2.33 16.05 ± 2.44 16.14 ± 2.10 16.38 ± 2.13 0.73

Data were mean micrometers±standard deviation(SD). According to analysis of variance with repeated measure ANOVA

Changes in circumpapillary retinal nerve fiber layer over time

In the APAC eyes, the superior, inferior and average RNFL thickness were significantly thicker in the affected eye compared to the contralateral eye at 1 day and 1 week after remission (P < 0.05, Fig. 1), and followed by a progressive thinning from 1 week (P=0.04, Fig. 1) to 6 months (P༝0.02, Fig. 1), and eventually reached a stable state.

Fig. 1.

Fig. 1

The changes of superior, inferior and average sector RNFL in the observation group over time. Changes in retinal nerve fiber layer (RNFL)at 1 day after remission and 1 week, 1 month, 3 months, 6 months and 1 year after surgery in acute primary angle closure (APAC) eyes. According to analysis of variance with the Kruskal-Wallis H test. * was compared with contralateral eye.

Changes in circumpapillary vessel density over time

Although inferior and average cpVD were significantly (P < 0.05, Table 3) lower in APAC eyes at multiple follow-ups within 1 year after remission compared with the contralateral eyes, no significant change in vessel density parameters of APAC eyes occurred at 1 day after remission (Fig. 2). The superior cpVD at 1 week after surgery was significantly different compared to the contralateral eye (P=0.031, Fig. 3), and was no significant differences at 1 week after surgery.

Table 3.

The changes of circumpapillary vessel density (%) in the observation group over time

Contralateral eye 1 day 1 week 1 month 3 months 6 months 1 year P Value
Superior sector 51.32 ± 2.82 47.59 ± 4.18 47.86 ± 5.54 46.17 ± 5.07 47.25 ± 5.80 45.76 ± 4.51 44.60 ± 4.02 0.004
Inferior sector 45.80 ± 3.54 46.20 ± 3.56 46.79 ± 2.80 45.86 ± 2.70 45.22 ± 2.36 45.69 ± 2.18 44.24 ± 2.24 <0.001
Average sector 48.35 ± 2.59 45.96 ± 3.41 46.19 ± 3.15 44.87 ± 3.72 44.72 ± 2.99 44.59 ± 2.41 43.50 ± 2.74 0.004

Data were mean micrometers±standard deviation(SD). According to analysis of variance with repeated measure ANOVA

Fig. 2.

Fig. 2

The changes of inferior sector cpVD in the observation group over time. According to analysis of variance with one-way ANOVA correction

Fig. 3.

Fig. 3

The changes of superior, inferior and average sector cpVD in the observation group over time. Changes in circumpapillary vessel density (cpVD) at 1 day after remission and 1 week, 1 month, 3 months, 6 months and 1 year after surgery in acute primary angle closure (APAC) eyes. According to analysis of variance with one-way ANOVA correction. * was compared with contralateral eye

Correlation analysis of peripapillary vessel density

At the final follow-up, the inferior cpVD in the APAC eyes was significantly correlated with the corresponding RNFL thicknesses (P < 0.01, Table 4). Additionally, the inferior cpVD in the observation group was significantly correlated with the visual field MD value (P < 0.01, Table 4). Moreover, visual field MD value was correlated with the duration of acute angleclosure glaucoma attact (P<0.01, Table 4). Furthermore, the superior, inferior, and average RNFL thicknesses in the APAC eyes at 1 year also showed negative correlations with the visual field MD value (Fig. 4).

Table 4.

The correlations of inferior cpVD(%) with other factors

Variable Inferior cpVD(%) InferiorRNFL(µm) Mean Deviation(dB)
IOP at presentation (mmHg)

^r=-0.380

p=0.132

^r=-0.252,

p=0.330

^r=-0.010,

p=0.970

Duration of the attack(h)

^r=0.075,

p=0.776

^r=-0.222

p=0.391

^r=-0.521,

p=0.032

Inferior

cpVD(%)

1

#r=0.606,

p=0.000

^r=-0.728,

p=0.000

Inferior

RNFL(µm)

#r=0.606,

p=0.000

1

^r=-0.521,

p=0.004

cpVD=circumpapillary vessel density; RNFL=retinal nerve fiber layer

# Pearson correlation and ^ Spearman’s rank correlation were applied

Fig. 4.

Fig. 4

The correlations of inferior cpVD with RNFL and MD. Correlations of circumpapillary vessel density (cpVD) with retinal nerve fiber layer (RNFL) and visual field mean deviation (MD) in acute primary angle closure (APAC) eyes. Simple linear regression showed a positive correlation of inferior, superior and average cpVD with inferior, superior and average RNFL and a negative correlation of visual field MD with inferior cpVD and RNFL thickness in APAC eyes

Discussion

APAC is an ocular disorder characterized by a sudden elevation in IOP. If promptly and effectively treated, it typically does not lead to significant visual impairment [13]. However, even the IOP was remission after APAC episode, delayed-onset optic nerve damage may still occur, and its initiating or contributing factors remain to be elucidated. OCTA enables the acquisition of retinal microcirculation images and facilitates reproducible qualitative and quantitative assessments of the vasculature in the optic nerve head (ONH) and peripapillary region [14, 15].

The current study characterized the long-term dynamic changes in peripapillary microcirculation following an episode of APAC, revealing a significant association between microvascular injury and structural functional deterioration. The results showed that inferior and average vessel density dropout was evident in APAC eyes within 1 year compared with contralateral eyes, but there was no change in cpVD parameters of the affected eyes after 1 day of IOP remission. While the superior cpVD reached stability after 1 week. In a prospective study, the cpVD at 2 months is significantly lower in APAC eyes after remission compared with the fellow eyes [16]. The previous study shows that vessel density decrease over 6 weeks after an APAC episode compared with the contralateral unaffected eyes [17, 18]. However, the exact time of cpVD stabilization and the alterations in cpVD at 1 day following resolution of APAC episode has not been systematically documented in previous studies. We speculated that high IOP have a greater impact on the changes in vessel density parameters after an APAC episode. The study found align with prior reports indicating reduced choroidal microcirculation in APAC eyes, where acute IOP elevation induces microvascular compromise [19]. In addition, experimental studies also support these observations: elevated IOP induces mechanical endothelial damage in retinal and optic nerve microvasculature. At critical IOP levels, prelaminar and retinal blood flow diminishes markedly, while retrolaminar flow increases—a hemodynamic shift causing shear stress-induced endothelial injury [20]. Another study reported, acute IOP spikes exceeding autoregulatory capacity impair capillary perfusion, leading to ischemia [21]. Structural alterations, such as posterior laminar displacement and scleral canal distortion under elevated IOP, may compress anterior laminar capillaries, reduce patency and compromise nutrient diffusion to the ONH.

Interestingly, we found that inferior cpVD was more sensitive. Previous studies reported, differences in microvascular injury patterns between angle closure and open angle glaucoma were observed: APAC exhibited more extensive superior and inferior microvascular involvement compared to focal dropout patterns in open-angle glaucoma. Particularly, the inferior circumpapillary microvasculature demonstrates greater susceptibility to ischemic damage [22, 23]. These are consistent with the current study which the inferior cpVD was stable at 1 day after the remission of APAC episode. During APAC episode, elevated IOP directly compresses the short posterior ciliary arteries supplying the inferior region, resulting in more pronounced reduction of inferior cpVD [17].

The current study demonstrated the superior, inferior, and average RNFL thickness initially showed thickening at 1 day, followed by a continuous decline from 1week to 6 months and eventually reached a stable state in the affected eyes. The previous studies demonstrated the potential mechanism may involve elevated IOP compressing the optic nerve vasculature. This leads to ischemia, hypoxia, and nutrient deficiency in retinal ganglion cells (RGCs) and their nerve fiber layers, ultimately resulting in axonal degeneration and RNFL thickness edema [17, 24]. The initial insult triggers secondary degeneration in the propagation of damage, resulting in RNFL thickness thinning [25]. A recent study on eyes with APAC found that significant average RNFL thickness increased at 1 week and reached a stable trend at 4 weeks [26]. We hypothesized that the observed variations in RNFL thickness changes may be attributed to differences in the initial severity of APAC episodes among the enrolled patients. However, another longitudinal study reported a significant decrease in superior, inferior, and average RNFL thickness within 2 weeks and 12 months [27]. We postulate that variations in follow-up intervals may account for the observed discrepancies in study outcomes, with more frequent follow-up assessments enabling more precise determination of stabilization timelines. Due to the dynamic changes in RNFL thickness following an APAC episode, consequently, evaluation of glaucoma progression using RNFL thickness parameters should be performed after 6 months.

We also demonstrated that cpVD in superior and inferior regions correlated with corresponding RNFL thickness and visual field MD at 1 year after remission. This is in agreement with a recent case-control study showing that cpVD is significantly correlated with VF loss in glaucomatous eyes with a history of APAC [28]. Whereas cpVD parameters demonstrated impaired perfusion as early as 1 day after APAC episode resolution, with reaching a stable trend during subsequent follow-up periods. In contrast, peripapillary RNFL thickness structure exhibited initial edematous thickening followed by progressive thinning. We found that the reduction in cpVD preceded RNFL thickness thinning and occurred even earlier than changes in visual field MD and cpVD at 1 day after remission demonstrated superior predictive value for glaucoma progression outcomes compared to later measurements. This suggests that cpVD holds diagnostic value comparable to RNFL thickness while demonstrating greater sensitivity than structural optic disc parameters and functional visual field metrics, consistent with previous reports by other investigators [29]. In another study, investigating changes in cpVD and RNFL thickness following APAC attacks, cpVD at 2 weeks was the best predictor of glaucoma progression. which was different with the current study [16]. The results showed that assessing the cpVD at 1 day after remission of an episode may enable more sensitive and earlier identification of APAC eyes with a higher risk of future glaucoma progression.

Longitudinally, the current study showed that there was no difference in cpVD between 1 day after remission of an episode and 1 week after surgery, indicating that the surgery had no intervention on retinal blood flow. This is in agreement with a recent longitudinal study suggesting that traditional phacoemulsification surgery shows no association with microcirculatory changes, reinforcing that peripapillary vascular loss arises from APAC intrinsic pathophysiology rather than surgical intervention [30].

This current study has limitations. First, the sample size is relatively small. Thirty unilateral APAC patients were enrolled, and the image quality or secondary angle closure or retinal disease of 9 patients did not meet the requirement for quantitative analysis. Thus, data from only 21 patients were available for analysis. Second, the available research data on acute intraocular pressure elevation due to corneal epithelial edema in APAC were insufficient. Third, the potential influence of phacoemulsification on cpVD could not be completely excluded. Fourth, unaffected eyes did not underwent lens extraction. This might have some influence on the quality of OCTA images and their measurements.

In conclusion, after 1 day of an APAC episode the inferior cpVD reduced and reached a stable state and the cpVD correlated with MD. Thus, the cpVD may more accurately reflect the extent of acute damage and may serve as a more sensitive indicator than RNFL thickness and MD, making it more suitable for early assessment and prediction of glaucoma progression. OCTA measurement of cpVD at 1 day after an APAC episode would be useful method for patients with higher risk of glaucoma progression in APAC eyes. The RNFL thickness reached a stable trend at 6 months after surgery. Therefore, OCT measurement of RNFL thickness after 6 months or more would be significant for APAC patients to observe the glaucoma progression. Longitudinal analysis confirms that it was important to increase the follow-up intervals for APAC patients. In addition, the current study demonstrated that APAC episodes trigger progressive peripapillary microvascular injury, independent of cataract surgery and strongly associated with structural and functional deterioration. Future studies should leverage emerging retinal or choroidal imaging technologies and AI-driven segmentation models to enhance peripapillary perfusion assessment. Prospective longitudinal studies may help to clarify the role of deep optic disc circulation in the pathogenesis of glaucoma.

Acknowledgements

Not applicable.

Author contributions

QH analyzed and interpreted the data, performed the initial drafting and review & editing of the manuscript, developed the methodology, conducted the investigation, and curated the data. YQ performed formal analysis and contributed to data curation, participated in writing – review & editing, formal analysis, and data curation. WLY provided the software and contributed to the methodology. YW contributed to writing – review & editing, visualization, and validation. JL performed validation, provided supervision, and contributed to conceptualization. FF analyzed and interpreted the data, performed the initial drafting and review & editing of the manuscript, developed the methodology, conducted the investigation, curated the data, and contributed to conceptualization. QH and YQ contributed to the work equally and should be regarded as co-first author. All authors read and approved the final manuscript.

Funding

The present study were supported by the Projects of Medical Science Research of Health Commission of Hebei Province, China (grant no.20220830), and the S&T Program of Hebei, China (grant no.18277753D).

Data availability

The datasets generated and analyzed during the current study are not publicly available due to it involves patient privacy but are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study adhered to the relevant provisions of the Declaration of Helsinki and had the approval of the Ethics Committee of Hebei General Hospital (review approval of the Ethics Committee of Hebei General Hospital: (2025) Research Ethics No. (072)). All patients provided written informed consent.” In Ethics Approval and Consent to Participate section in Declarations.

Patient consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Presentation at a conference: Not presented at any conference.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Qian Hao and Yuan Qin contributed to the work equally and should be regarded as co-first author.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated and analyzed during the current study are not publicly available due to it involves patient privacy but are available from the corresponding author on reasonable request.


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