Assessment of retinal and choroidal microcirculation after unilateral recession–resection surgery for horizontal strabismus by swept-source optical coherence tomography angiography

This study explored the possible hemodynamic changes of the retina and choroid after horizontal strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). 32 eyes of 32 patients who underwent unilateral horizontal rectus muscle recession–resection surgery were included. SS-OCTA examinations were performed preoperatively and one week postoperatively. Several OCTA measurements were used, including vessel density (VD) of the superficial vascular complex (SVC), VD of the deep vascular complex (DVC), VD of the choriocapillaris (CC), choroidal vascular index (CVI) and choroidal thickness (CT). No significant change in VD of SVC, DVC, and CC was observed whereas CT increased significantly with CVI unchanged. Recession–resection surgery for horizontal strabismus seemed not to significantly influence the microcirculation of the retina and CC in the early postoperative period. However, choroidal thickening happened with a constant CVI probably due to the postoperative inflammation. Further studies are needed to investigate the long-term effects of unilateral recession–resection surgery for horizontal strabismus on the microcirculation of the retina and choroid.

www.nature.com/scientificreports/Therefore, the purpose of this study is to use advanced SS-OCTA to evaluate the possible hemodynamic changes of the retina and choroid after unilateral recession-resection surgery for horizontal strabismus.

Materials and methods
This is a prospective observational study.This study was conducted in accordance with tenets of the Declaration of Helsinki and was approved by the Ethical Review Committee of Renmin Hospital of Wuhan University.Informed consent was obtained for all participants before recruitment.For participants of 18 years or older, the informed consent was signed by themselves, and for those under 18 years, the informed consent was signed by their parents or guardians.
Participants who underwent unilateral horizontal rectus muscle surgery were enrolled at Renmin Hospital of Wuhan University from May 2022 to October 2022.All the diagnosis was made by an experienced specialist (Y.H.X.) after performing comprehensive examinations on all patients.The examinations included intraocular pressure, ocular motility, mydriatic optometry under cycloplegia, axial length, slit-lamp biomicroscopy anterior segment examination, dilated fundus examination, and strabismus tests (cover-uncover test, prism and alternate cover test, and Krimsky test).Radiological examinations (cranial CT and MRI) were performed when necessary.All patients were horizontal strabismus and had received unilateral recession-resection surgery.All strabismus operations were performed by an experienced expert (Y.H.X.) following standard procedures.Patients wouldbe excluded if they had: (1) other ocular diseases such as intraocular inflammation and heritable ocular diseases; (2) ocular hypertension with intraocular pressure > 21 mmHg; (3) a history of strabismus surgery or intraocular surgery; (4) refractive error < − 3 dioptres; (5) ocular media opacification that might affect the accurate measurement of OCTA; (6) any systemic disease that could affect the eye such as diabetes and hypertension; (7) a history of smoking, alcohol abuse, or drug problems; and (8) OCTA images with signal strength less than 7/10.SS-OCTA examinations were conducted preoperatively and one week after surgery using the VG100 system (SVision Imaging, Ltd., Luoyang, China) by two trained examiners (Y.M. and Y.S.X.).Each participant was asked to avoid having cola, coffee, or any other caffeine-containing drink within 24 h before the examination.All participants were required to have a rest for 10 min before the OCTA examination.OCTA scans were conducted between 1:00 p.m. and 6:00 p.m. to minimize the influence of diurnal variation of the choroidal structure 17 .
The SS-OCTA device had a scan rate of 100,000 A-scans per second and a central wavelength of approximately 1050 nm.OCTA examinations were performed using the three-dimensional scan protocol with a 6 mm×6 mm scan area (1024 × 1024 B-scans) centered on the fovea.Built-in eye-tracking software was used to reduce eye motion artifacts.The segmentation of the retinal and choroidal layers was achieved using a validated built-in segmentation algorithm and was then carefully checked and calibrated by two experienced clinicians (Y.H.X. and D.H.H.).
The macula was stratified into three subregions as follows: the foveal region defined by a circle with a diameter of 1 mm centered at the foveal center, the parafoveal region defined by the annular area between 2 circles with diameters of 1 and 3 mm, and the perifoveal region defined by the annular area between 2 circles with diameters of 3 and 6 mm (Fig. 1).For this study, the following OCTA measurements were used: vessel density (VD) of the superficial vascular complex (SVC), VD of the deep vascular complex (DVC), VD of the choriocapillaris (CC),

Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethical Review Committee of Renmin Hospital of Wuhan University.

Informed consent
Informed consent was obtained from all subjects involved in the study.

Results
A total of 32 eyes of 32 patients were included in this study, among which 19 (59.4%) were female.The average age of the participants was 27.9 ± 11.8 years.All patients were horizontal strabismus (exotropia or endotropia).All patients had unilateral horizontal rectus muscle surgery (recession-resection).
Table 1 showed the preoperative and postoperative measurements of retinal vascular density at the level of SVC and DVC in all the macular subregions.No significant difference was observed between the preoperative and postoperative measurements of VD of SVC and DVC in all the subregions (all p > 0.05).
Table 2 demonstrated the preoperative and postoperative choroidal measurements.No significant difference was detected between the preoperative and postoperative VD of CC values and CVI values in any of the macular subregions (all p > 0.05).However, the CT in all the subregions increased significantly after strabismus surgery (all p < 0.001).

Discussion
In this study, we used swept-source OCTA to evaluate the potential hemodynamic changes of the retina and choroid in patients who underwent strabismus surgery.We observed no significant changes in the hemodynamic parameters of the retina (VD of SVC and DVC), or choroid (CVI and VD of CC) in any examined macular subregions.However, CT increased significantly in all the subregions one week following surgery.
Earlier researchers have tried to investigate the impact of strabismus surgery on ocular hemodynamics in different ways.Based on color Doppler imaging, some studies have investigated the hemodynamic changes in the retrobulbar blood flow following strabismus surgery and obtained conflicting conclusions 13,14,20 .Lee et al. found that strabismus surgery increased the blood flow of the ophthalmic artery (OA) on postoperative day 1 but the blood flow went back to baseline level one week after surgery and remained stable at one month 13 .Nevertheless, Akyüz et al. suggested that strabismus surgery did not have a measurable effect on the retrobulbar blood flow at both postoperative day 1 and day 30 14 .However, it should be noted that orbital color Doppler imaging has poor sensitivity when measuring vascular parameters and the accuracy and stability highly depend on the experience of the examiners.Also, color Doppler imaging can only indirectly infer the blood flow of larger vessels,  10 .They found the mean CRA equivalent increased significantly on postoperative day 1 but returned to baseline level at one week.However, the change of CRA equivalent might not directly represent the change of retinal microcirculation, and the use of routinely taken color fundus photographs to assess the retinal vascular diameters overlooked the systolic or diastolic effect on retinal vascular diameter.OCTA has several advantages over the use of color Doppler imaging or color fundus photographs for studying hemodynamics and structure alterations after strabismus surgery.Based on motion signal differences in successive B-scans at the same location, OCTA provided us with a fast and non-invasive imaging technology to evaluate the retinal and choroidal structures and microcirculation 21 .Besides, the high resolution in the axial direction of OCTA can help analyze the microcirculation of the retina and choroid in different layers, such as the SVC and DVC of the retina as well as CC and CVI of the choroid 21 .Moreover, OCTA parameters had good repeatability for both healthy and diseased individuals 22,23 .To our knowledge, only a few studies have investigated the potential hemodynamic changes of the macula after strabismus surgery 9,16,24 .Inal et al. evaluated the retinal vascular diameter changes preoperatively and 3 months postoperatively 24 .They found a statistically significant increase in VD of both the superficial and deep capillary plexus postoperatively.Çelik and colleagues observed no significant changes in retinal hemodynamics one week and one month postoperatively but detected a transient increase of the VD of CC at one week 9 .In a recent study, Vagge et al. assessed the macular blood flow on the first day postoperatively and one month postoperatively 16 .They showed a transitory increase of blood flow in the deep capillary plexus and CC only atday 1 following surgery.Nonetheless, CVI and CT were not investigated in these studies.Besides, our study design was more stringent.We ruled out factors that might affect the chorioretinal microcirculation and choroid thickness as much as possible, such as systemic disease, smoking, drug or alcohol abuse, caffeine-containing products, physical exercise, and diurnal variation of the choroid 17,[25][26][27] .
Our study suggests that recession-resection surgery for horizontal strabismus will not significantly impact the microcirculation of the retina and CC in the early postoperative period.However, choroidal thickening was found at the foveal, parafoveal, and perifoveal regions whereas the CVI remained constant.Since CVI is defined as: where V total is the total choroidal volume, CVV is the choroid vessel volume, and CSV is the choroidal stroma volume.And the increase in CT represented the increase of V total .According to Eq. ( 1), only when the CVV and V total increased at the same time could CVI remain constant.It can be further inferred that the CSV has also increased, otherwise, CVI would not remain unchanged.A possible explanation for this phenomenon is periocular inflammation.Choroidal thickening after cataract surgery has been widely reported and postoperative inflammation was considered an important cause [28][29][30] .Besides, many inflammatory disorders have been known to lead to choroidal thickening 31,32 .Thus, it is likely that the increase in CT following strabismus surgery resulted from postoperative inflammation.Suture materials used in strabismus surgery were reported to cause postoperative inflammation [33][34][35] .Besides, surgical procedures would inevitably cause damage to blood vessels and muscles, resulting in a series of reactions such as the secretion of proinflammatory cytokines and activation of neutrophils 36,37 .Then vasodilatation, increase of vascular permeability, and fluid exudation will happen via a complex immune cascade 36,38 .The dilation of choroid vessels would explain the increase of CVV whereas the higher vascular permeability could contribute to an elevated fluid exudation from vessels into the stroma, causing an increased CSV.The simultaneous rise of CSV and CVV resulted in the increased CT and constant CVI observed in this study, although further research is needed to verify this hypothesis.
Our study has several limitations.First, this is a single-center study with a limited number of patients, thus further studies of larger sample sizes are needed.Another limitation is that we evaluated the retinal and choroidal microcirculation only one week after surgery thus the long-term effect of recession-resection surgery for  www.nature.com/scientificreports/horizontal strabismus on the retina and choroid needs further study.Finally, since we included patients with horizontal strabismus (esotropia and exotropia), possible differences between these two types of horizontal strabismus may have been overlooked, which would be an interesting topic for future exploratory work.While we acknowledge these limitations, our results may offer some new insights into the dispute over whether chorioretinal changes exist after strabismus surgery.

Conclusions
In summary, we showed that recession-resection surgery for horizontal strabismus did not significantly impact the microcirculation of the retina and CC in the early postoperative period.However, choroidal thickening happened in the case of a constant CVI which is likely due to postoperative inflammation.Further studies with a longer follow-up are needed to investigate the long-term effects of recession-resection strabismus surgery on the retina and choroid.

Table 1 .
Measurements of the superficial vascular complex and deep vascular complex.SVC superficial vascular complex, DVC deep vascular complex.*Wilcoxon signed-rank test.Others: paired sample t-test..g., the OA and central retinal artery (CRA), through parameters such as peak systolic blood flow velocity and resistivity index, thus being unable to well detect the retinal and choroidal microcirculation.Zhou et al. used a computer-assisted quantitative assessment software to assess the retinal vessel caliber changes on color fundus photographs Vol:.(1234567890) Scientific Reports | (2023) 13:19247 | https://doi.org/10.1038/s41598-023-46670-3www.nature.com/scientificreports/e

Table 2 .
Measurement of choroidal parameters.VD vascular density, CC choriocapillaris, CVI choroidal vascular index, CT choroidal thickness.*Wilcoxon signed-rank test.Others: paired sample t-test.Bolded P values are of statistical significance.