{"paper_id":"38b94a92-df56-4348-b259-09e4eb94291d","body_text":"Dose-Related, Layer-Specific Alterations in Macular Microcirculation Following Horizontal Rectus Muscle Surgery: A Three-Dimensional OCT Angiography Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dose-Related, Layer-Specific Alterations in Macular Microcirculation Following Horizontal Rectus Muscle Surgery: A Three-Dimensional OCT Angiography Study Xiyu Zhao, Jingjing Jiang, Jiaqi Qi, Zhao Wang, Li Li, Xiaogang Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9039006/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: To investigate dose-related, layer-specific, and regional changes in macular microcirculation after horizontal rectus muscle surgery using three-dimensional optical coherence tomography angiography (3D-OCTA). Methods: This prospective observational study included 40 eyes from 30 patients. Eyes were grouped by cumulative surgical dose (supranormal ≥14 mm, n=15; conventional <14 mm, n=25). Macular 6×6-mm OCTA was obtained preoperatively and at postoperative day 1, week 2, and week 6. Three-dimensional vessel volume density (VVD), vessel skeleton density (VSD), and vessel diameter index (VDI) were quantified in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) across ETDRS subfields and a whole-scan region. Longitudinal changes were assessed using generalized estimating equations with Holm-adjusted contrasts versus baseline, and dose–response relationships using Spearman correlation. Results: Supranormal-dose eyes showed early reductions in VVD and VSD of the DCP on day 1, most evident in outer-ring sectors and the whole-scan region. Increases in both the SVP and ICP emerged at week 2, while residual deep-layer abnormalities persisted in selected sectors at week 6. Conventional-dose eyes showed no early decline but demonstrated compensatory increases at week 2 and sustained DCP dilation through week 6. Higher dose correlated with smaller ΔVVD and ΔVSD responses in nasal and superior sectors and greater temporal deep-layer ΔVDI. Conclusions: Horizontal rectus muscle surgery induces dose-sensitive macular microvascular alterations, with higher doses preferentially affecting the DCP and showing slower recovery in selected regions. 3D-OCTA enables sensitive detection of these changes and may assist in surgical planning and postoperative monitoring. Strabismus surgery Optical coherence tomography angiography Macular microcirculation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Key Message What is known • Postoperative alterations in ocular blood flow have been reported after strabismus surgery, but macular microvascular findings remain heterogeneous across studies. What this study adds • Three-dimensional OCTA demonstrates dose-related, layer-specific changes in macular microcirculation following horizontal rectus muscle surgery. • Higher cumulative surgical dose is associated with more pronounced early alterations in deep capillary plexus perfusion metrics. • Regional heterogeneity suggests sector-specific dose sensitivity within the macula. Introduction Strabismus surgery is routinely performed to correct ocular misalignment and restore binocular vision. However, horizontal rectus muscle procedures inevitably disrupt anterior ciliary artery flow and trigger postoperative inflammatory responses. These perioperative perturbations may alter ocular hemodynamics, including retinal and macular microcirculation. [ 1 ] Early Doppler-based hemodynamic assessments showed transient postoperative changes in bulk blood flow of larger retrobulbar vessels such as the ophthalmic artery, typically returning to baseline within days to weeks, but provided limited insight into capillary-level responses within the macula. [ 2 , 3 ] The advent of optical coherence tomography angiography (OCTA) has enabled noninvasive, in vivo visualization of the macular microvasculature. However, previous OCTA studies have reported heterogeneous postoperative patterns, with variability in the direction and timing of changes, as well as inconsistencies across macular subfields and vascular plexuses. [ 4 – 6 ] These discrepancies may partly reflect differences in follow-up schedules and the predominant use of two-dimensional vessel-density summaries. In contrast, our three-dimensional OCTA (3D-OCTA) approach leverages the full angiographic volume to quantify vessel volume density, vessel skeleton density, and caliber-sensitive changes, enabling a more comprehensive assessment of postoperative microvascular alterations. Importantly, the potential influence of surgical dose, defined as the cumulative extent of muscle recession and/or resection, on postoperative microcirculatory responses has received little attention. Whether larger surgical doses induce greater microvascular impairment or alter recovery trajectories remains unclear. The macular microvasculature is highly compartmentalized, with pronounced layer-specific and regional heterogeneity. The superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) differ in anatomical configuration, perfusion pressure, and regulatory capacity, suggesting that each plexus may respond differently to surgical stress. [ 7 ] Three-dimensional OCTA (3D-OCTA) enables quantitative assessment of microvascular architecture beyond conventional two-dimensional metrics by incorporating vessel volume, skeletonized length, and caliber, thereby providing a more comprehensive characterization of postoperative vascular remodeling. [ 8 ] In this study, we used 3D-OCTA to longitudinally characterize layer- and region-specific changes in macular microcirculation after horizontal rectus muscle surgery. Using generalized estimating equation (GEE) modeling, we compared postoperative trajectories across eyes stratified by cumulative surgical dose and evaluated whether microvascular responses varied with surgical dose. Methods Study Design and Participants This prospective study recruited patients undergoing horizontal rectus muscle surgery at Shanxi Eye Hospital from April to August 2024, with ≥ 6 weeks of postoperative follow-up. The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shanxi Eye Hospital affiliated with Shanxi Medical University (approval No. SXYYLL-KSSC051). Exclusion criteria included prior ocular surgery; best-corrected visual acuity < 1.0; spherical equivalent (SE) ≤ − 6.0 diopters (D); systemic vasculopathy, such as diabetes or hypertension; developmental or neurologic disorders; poor OCTA image quality or artifacts; and concurrent oblique muscle surgery. All patients underwent standard preoperative ophthalmic examinations, including visual acuity, refraction, slit-lamp biomicroscopy, funduscopy, tonometry, motility assessment, and strabismus angle measurement at near and distance. Surgical Procedures All procedures were performed under microscopy by a single experienced surgeon. Techniques included medial or lateral rectus recession, resection, or combined recession-resection, tailored to the magnitude of the deviation. Medial rectus adjustments were ≤ 8 mm; lateral rectus adjustments were ≤ 10 mm. Eyes were grouped by cumulative dose for the supranormal dose group (≥ 14 mm) or the conventional dose group (< 14 mm). OCTA Acquisition and Segmentation A trained operator acquired 6×6-mm macular OCTA scans (SPECTRALIS II OCT system, Heidelberg Engineering, Heidelberg, Germany) preoperatively and on postoperative day 1, week 2, and week 6 under controlled illumination. The macula was segmented according to the Early Treatment Diabetic Retinopathy Study (ETDRS) standard grid into the central fovea (F); an inner ring subdivided into superior, nasal, inferior, and temporal sectors (IS, IN, II, IT); and an outer ring subdivided into superior, nasal, inferior, and temporal sectors (OS, ON, OI, OT) (Fig. 1 ). Additionally, metrics were computed for the entire 6 × 6 mm macular scan area. Retinal vascular plexuses were segmented into the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) using the standardized boundaries proposed by Campbell et al. [ 9 ] In brief, the superficial vascular plexus (SVP) was defined within the more internal portion of the ganglion cell complex, the intermediate capillary plexus (ICP) spanned the remaining outer one-fifth of the ganglion cell complex together with the inner half of the inner nuclear layer (INL), and the deep capillary plexus (DCP) extended from the outer half of the INL through the full thickness of the outer plexiform layer (OPL). Quantitative analyses were performed for SVP, ICP, and DCP in each ETDRS sector as well as in the whole-scan region. Three-Dimensional Vascular Metrics Three-dimensional vascular parameters were extracted from the reconstructed OCTA volume within each analyzed sector and plexus. Vessel volume density (VVD) was defined as the ratio of retinal vessel volume to the total retinal volume in the measured region, capturing both vessel length and caliber and providing an estimate of actual vessel density. Vessel skeleton density (VSD) was defined as the total vessel length per unit tissue volume, reflecting vessel density primarily based on vessel length. Vessel diameter index (VDI) was calculated as the ratio of total vessel volume to total vessel length (equivalently, VVD/VSD), reflecting the mean vessel caliber in the region and being sensitive to vessel dilation on OCTA. To minimize ocular magnification effects related to axial length, the nominal OCTA scan size was rescaled using the Littmann approach together with the modified Bennett formula. For the Heidelberg platform, the default axial length was set to 24.385 mm. An area-based correction factor was computed as \\({\\left(\\frac{A{L}_{actual}-1.82}{A{L}_{default}-1.82}\\right)}^{2}\\) , and the corresponding linear scaling factor was derived as \\(\\frac{A{L}_{actual}-1.82}{A{L}_{default}-1.82}\\) . The ETDRS sector boundaries and whole-scan dimensions were adjusted according to this scaling factor before quantitative analysis. [ 10 , 11 ] Statistical Analysis Statistical analyses were performed in SPSS 28.0. Normality was assessed using the Shapiro–Wilk test. Baseline characteristics were compared using independent-samples t-tests and χ² tests. Within each dose group, longitudinal changes in VVD, VSD, and VDI were evaluated using GEE with time as the repeated factor and age as a covariate. An independent working correlation structure was applied to account for repeated measurements and potential inter-eye correlation. Post hoc simple contrasts comparing each follow-up visit to baseline were adjusted using the Holm method. Spearman rank correlation analysis was performed to assess the relationship between surgical dose and postoperative changes in macular microcirculation. Time points were classified as postoperative day 1, 2 weeks, and 6 weeks, with Δ values representing changes relative to baseline. A two-tailed P-value < 0.05 was considered statistically significant. Results Clinical Characteristics in this study Baseline demographic and clinical characteristics were similar between the supranormal-dose (≥ 14 mm) and conventional-dose (< 14 mm) groups (Table 1 ). There were no statistically significant between-group differences in sex, age, or spherical equivalent refractive error (all P > 0.05). Table 1 Baseline demographic and clinical characteristics of the study eyes. Gender Supranormal dose (≥ 14 mm) group n = 15 Conventional dose (< 14 mm) group n = 25 \\({{\\chi}}^{2}/t\\) \\(P\\) 0.444 0.505 Male 8(53.33) 16(64.00) Female 7(46.67) 9(36.00) Age (y) 22.73 ± 8.96 20.92 ± 8.88 0.623 0.537 Spherical equivalent (D) -2.08 ± 2.29 -2.99 ± 2.29 1.213 0.233 Data are presented as mean ± SD or n (%). P values were obtained from independent-samples t tests or χ² tests, as appropriate. SD, standard deviation D, diopters. Longitudinal Changes in VVD In the supranormal-dose group, GEE showed significant early decreases in DCP VVD on postoperative day 1 in the outer superior and outer temporal sectors, as well as in the whole-scan region, indicating early deep-layer hypoperfusion. At 2 weeks, VVD increased transiently in the ICP and SVP, predominantly in the superior and nasal sectors of both the inner and outer rings, with a concurrent increase in the whole-scan region. By 6 weeks, a residual reduction in DCP VVD persisted in the outer temporal sector and remained detectable at the whole-scan level. The conventional-dose group showed no early reductions in VVD. At 2 weeks, VVD increases were mainly concentrated in the inferior-related sectors; meanwhile, whole-scan VVD increased across the DCP, ICP, and SVP layers. By 6 weeks, VVD generally trended toward stabilization; however, several DCP sectors remained elevated in the conventional-dose group (Fig. 2 ). Longitudinal Changes in VSD VSD trajectories largely paralleled those of VVD. Supranormal-dose eyes exhibited early reductions in deep-layer VSD in the outer superior and outer temporal sectors, as well as in the whole-scan region on day 1. This was followed by transient increases at 2 weeks, primarily in the ICP across multiple sectors, along with additional SVP increases. No significant differences from baseline were detected at 6 weeks. Conventional-dose eyes showed delayed increases in VSD at 2 weeks, with DCP VSD remaining elevated in selected outer-ring sectors at 6 weeks (Fig. 3 ). Longitudinal Changes in VDI In the supranormal-dose group, VDI decreased on postoperative day 1 mainly in the ICP, with a concurrent whole-scan decrease in the DCP. At 6 weeks, a residual reduction persisted in the inner inferior sector, accompanied by an increase in the foveal DCP. In the conventional-dose group, VDI increased predominantly in the DCP from 2 weeks through 6 weeks across multiple regions, including the whole-scan area (Fig. 4 ). Dose-Response Correlation Analysis Spearman analyses revealed region- and layer-specific dose–response relationships. Higher surgical doses correlated negatively with ΔVVD and ΔVSD in predominantly nasal and superior sectors, indicating that larger doses were associated with smaller compensatory increases or greater postoperative loss (Supplementary Figure S1 and S2). In contrast, positive correlations were observed for ΔVDI at 2 weeks in selected regions, suggesting greater caliber increases with higher doses. At 6 weeks, negative correlations between dose and foveal DCP ΔVDI suggested protracted recovery in higher-dose cases (Supplementary Figure S3). In the scatterplots, linear fits are shown for visualization only. The full Spearman correlation results for each region and timepoint are provided in Supplementary Table S4, S5 and S6. Discussion This study suggests dose-related changes in macular microcirculation after horizontal rectus muscle surgery. Supranormal-dose eyes showed more prominent microvascular disturbance, with a greater tendency toward early deep-layer reductions in VVD and VSD and clearer dose–response patterns in selected sectors and time points. Specifically, higher surgical doses were associated with more pronounced postoperative decreases in VVD or VSD or less evident compensatory increases. In contrast, changes in the conventional-dose group were predominantly delayed and compensatory and tended to recover over follow-up. Overall, these findings suggest that macular microcirculation exhibits dose sensitivity and may indicate a shift from compensatory adaptation toward microvascular injury at higher surgical doses. Prior OCTA studies in other retinal conditions have demonstrated that capillary loss is associated with poorer visual function. [ 12 ] Therefore, the more prominent deep-layer abnormalities observed in supranormal-dose eyes may indicate a prolonged functional recovery period, supporting closer OCTA monitoring in higher-dose cases. Across analyses, the DCP appeared to be the most responsive and vulnerable plexus after surgery. In the supranormal-dose group, early reductions were most consistently observed in DCP VVD and VSD, especially in the outer-ring sectors and at the whole-scan level. In contrast, the SVP and ICP showed relative preservation, with transient compensatory increases at later visits. This layer-specific pattern highlights the DCP as a key site of postoperative microvascular stress and suggests that the deeper retinal circulation is especially sensitive to surgical perturbation. Longitudinal evaluation suggested dose-related differences in postoperative microvascular patterns. Eyes receiving supranormal doses tended to show earlier deep-layer hypoperfusion, less prominent compensatory responses in some sectors, and residual abnormalities in selected deep-layer regions by 6 weeks. By comparison, conventional-dose eyes more often exhibited delayed compensatory hyperperfusion and vasodilation, with many parameters trending toward stabilization over follow-up, although some sector- and layer-specific changes persisted. Collectively, these observations support a dose-sensitive microvascular response and suggest that higher surgical doses may shift the balance toward greater microvascular stress and slower recovery. The underlying mechanisms may relate to intraoperative disturbance of the anterior ciliary circulation and adjacent tissues, which primarily supply the anterior segment and influence posterior segment perfusion through collateral pathways. [ 13 ] In supranormal-dose procedures, extensive vascular transection and tissue trauma may overwhelm compensatory collateral capacity, resulting in downstream macular hypoperfusion. The apparent susceptibility of the DCP may reflect both its anatomical position and limited hemodynamic reserve. It is organized as a predominantly planar capillary network with relatively limited anastomotic and collateral redundancy. Additionally, DCP flow is thought to operate under lower perfusion pressure with a narrower autoregulatory reserve, which may render it more sensitive to ischemic stress (Fig. 5 ). [ 14 – 17 ] Overall, these findings indicate region-specific dose sensitivity within the macula: some sectors appear more prone to persistent alterations, while others may show recovery through adaptive remodeling. Notably, the nasal and superior macular sectors exhibited significant negative dose–response relationships in perfusion metrics at specific time points, indicating greater sensitivity to surgical trauma. This sensitivity may be related to the asymmetric macular microvascular architecture and limited collateral support in these regions. [ 18 ] In contrast, the temporal deep-layer measures showed positive dose–response relationships for ΔVVD and ΔVDI at postoperative week 2, consistent with increased density and caliber associated with higher doses. Despite these general patterns, substantial interindividual variability was observed during these adaptive or recovery processes. From a clinical perspective, these findings inform surgical decision-making. In patients with preexisting microvascular compromises, such as diabetes mellitus, hypertension, or other conditions that impair microcirculatory regulation, vascular reserve may be diminished. In such individuals, supranormal-dose strabismus surgery may increase the likelihood of prolonged deep-layer perfusion alterations, which could be clinically significant even in the absence of overt complications. Therefore, careful consideration of surgical dose, alternative techniques, or staged strategies may be warranted in high-risk populations. Strabismus often requires reoperation, with timing decisions typically guided by ocular alignment, muscle adaptation, and scar maturation; however, retinal microcirculation is rarely considered. Prior studies have reported heterogeneous postoperative hemodynamic time courses using different modalities. [ 19 – 21 ] Our results suggest that compensatory microvascular responses are most prominent around 2 weeks postoperatively, with many regions approaching an early stabilization phase by approximately 6 weeks, particularly following conventional-dose surgery. Notably, certain deep-layer alterations after supranormal-dose procedures persisted at 6 weeks, indicating slower vascular recovery in eyes receiving higher doses. Although routine reoperation is generally scheduled several months later, these findings provide a physiological context for postoperative monitoring and may be especially relevant when early re-intervention is unavoidable, underscoring the need for caution during the first 6 weeks. These results also help refine postoperative monitoring. OCTA at postoperative day 1 can capture acute perfusion disturbances, an intermediate assessment around 2 weeks can characterize compensatory peaks, and a follow-up around 6 weeks can evaluate recovery trends or residual deficits. This tiered schedule may be particularly useful for high-dose cases or patients with vascular comorbidities. Several limitations warrant acknowledgment. First, the sample size was moderate, which may have limited more detailed subgroup analyses. Second, the 6-week follow-up captured acute and subacute dynamics but may have overlooked longer-term remodeling or sequelae. Third, analyses were performed at the eye level, and the inclusion of some bilateral cases may have introduced inter-eye non-independence. Finally, our focus on macular microcirculation precluded evaluation of anterior segment or choroidal perfusion. Future studies with larger cohorts, extended longitudinal follow-up, and multimodal imaging, including anterior segment OCTA and dedicated choroidal flow assessment, are warranted to better characterize comprehensive ocular hemodynamic responses to strabismus surgery. Declarations Funding Xiyu Zhao, Shanxi Provincial Department of Education, Postgraduate Practical Innovation Project, 2024SJ167 Junhong Li, Shanxi Provincial Department of Science and Technology, Central Guiding Local Technology Development Introduction In the era of rapid technological advancement of Shanxi Provincial department of Science and Technology, YDZJSX2024B013 Competing Interests The authors declare that they have no competing interests. Human Ethics and Consent to Participate The study was approved by the Ethics Committee of Shanxi Eye Hospital affiliated with Shanxi Medical University (Approval No. SXYYLL-KSSC051) and adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal guardians. Clinical Trial Registration Clinical trial number: Not applicable. Author Contribution X.Y.Z. collected the data and drafted the main manuscript.J.J.J. contributed to study conception and manuscript writing. J.Q.Q. performed image processing. Z.W. supervised the image analysis and provided methodological guidance. L.L. provided academic supervision and critical input throughout the study. X.G.W. facilitated data acquisition and provided academic supervision and critical input throughout the studythe clinical setting for patient recruitment. J.H.L. contributed to the study design oversight, provided senior academic guidance, and facilitated the clinical setting for patient recruitment. Data Availability The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and institutional restrictions but are available from the corresponding author on reasonable request. References Huang YT, Lin SC, Huang LY, et al. Incidence, Risk Factors and Management of Postoperative Complications in Horizontal Strabismus Surgery. Semin Ophthalmol. 2024;39(2):143–9. Pelit A, Barutçu O, Oto S, Aydin P. Investigation of hemodynamic changes after strabismus surgery using color Doppler imaging. J AAPOS. 2002;6(4):224–7. Lee NH, Lee SN. Investigation of hemodynamic changes in the ophthalmic artery using color Doppler imaging after strabismus surgery. Korean J Ophthalmol. 2005;19(3):208–12. Vagge A, Nucci P, Ferro Desideri L et al. Evaluation of macular vessel density changes after strabismus surgery using optical coherence tomography angiography. J AAPOS. 2022. 26(2): 71.e1-71.e4. Inal A, Yilmaz I, Ocak OB, et al. Optical Coherence Tomography Angiography: Are There Any Changes in Measurements After Strabismus Surgery. J Pediatr Ophthalmol Strabismus. 2019;56(2):95–100. Huseyinhan Z, Ozcaliskan S, Gurez C, Artunay O. Retinal and choroidal microvasculature is altered after strabismus surgery. Eur J Ophthalmol. 2022: 11206721221137156. Chandrasekera E, An D, McAllister IL, Yu DY, Balaratnasingam C. Three-Dimensional Microscopy Demonstrates Series and Parallel Organization of Human Peripapillary Capillary Plexuses. Invest Ophthalmol Vis Sci. 2018;59(11):4327–44. Liu Y, Tang Z, Li C, et al. AI-based 3D analysis of retinal vasculature associated with retinal diseases using OCT angiography. Biomed Opt Express. 2024;15(11):6416–32. Campbell JP, Zhang M, Hwang TS, et al. Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography. Sci Rep. 2017;7:42201. Sampson DM, Gong P, An D, et al. Axial Length Variation Impacts on Superficial Retinal Vessel Density and Foveal Avascular Zone Area Measurements Using Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2017;58(7):3065–72. Tian X, Liu Y, Ning X, et al. 3D-OCTA Evaluation of Retinal Microcirculation Abnormalities in the Macular Region of Eyes With Anisometropic Amblyopia. Transl Vis Sci Technol. 2025;14(10):4. Feng J, Yang X, Xu M, et al. Association of Microvasculature and Macular Sensitivity in Idiopathic Macular Epiretinal Membrane: Using OCT Angiography and Microperimetry. Front Med (Lausanne). 2021;8:655013. Olver JM, Lee JP. The effects of strabismus surgery on anterior segment circulation. Eye (Lond). 1989. 3 (Pt 3): 318 – 26. Lavia C, Bonnin S, Maule M, Erginay A, Tadayoni R, Gaudric A. VESSEL DENSITY OF SUPERFICIAL, INTERMEDIATE, AND DEEP CAPILLARY PLEXUSES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina. 2019;39(2):247–58. Balaratnasingam C, An D, Hein M, Yu P, Yu DY. Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy. Prog Retin Eye Res. 2023;94:101134. Lavia C, Mecê P, Nassisi M, et al. Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography. Sci Rep. 2020;10(1):1474. Fouquet S, Vacca O, Sennlaub F, Paques M. The 3D Retinal Capillary Circulation in Pigs Reveals a Predominant Serial Organization. Invest Ophthalmol Vis Sci. 2017;58(13):5754–63. Yu PK, Mammo Z, Balaratnasingam C, Yu DY. Quantitative Study of the Macular Microvasculature in Human Donor Eyes. Invest Ophthalmol Vis Sci. 2018;59(1):108–16. Gül C, Erşan H, Karapapak M, Güven D. Optical Coherence Tomography Angiography Evaluation of Retinal and Choroidal Microvascular Morphological Changes Following Strabismus Surgery. J Pediatr Ophthalmol Strabismus. 2024;61(6):397–403. Emekli DT, Aydamirov AS. Investigation of the effects of single and two-muscle horizontal rectus surgeries on macular microvasculature. Graefes Arch Clin Exp Ophthalmol. 2025;263(1):217–23. Yasuda S, Takai Y, Yasuda Y, et al. Quantitative Evaluation of Changes in Retinal and Choroidal Blood Flow Following Strabismus Surgery. Transl Vis Sci Technol. 2025;14(3):12. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable.docx SupplementaryFigure.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 02 Apr, 2026 Editor invited by journal 07 Mar, 2026 Submission checks completed at journal 06 Mar, 2026 Editor assigned by journal 06 Mar, 2026 First submitted to journal 05 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-9039006\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":618382262,\"identity\":\"fdcceaa0-19e3-4ab8-a49d-9fc0ae58ed89\",\"order_by\":0,\"name\":\"Xiyu Zhao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Key Laboratory of Major Diseases in Children, Ministry of Education\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiyu\",\"middleName\":\"\",\"lastName\":\"Zhao\",\"suffix\":\"\"},{\"id\":618382263,\"identity\":\"9e3f1e9e-d7e2-45e1-92d0-8673fdb6b217\",\"order_by\":1,\"name\":\"Jingjing Jiang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Key Laboratory of Major Diseases in Children, Ministry of Education\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jingjing\",\"middleName\":\"\",\"lastName\":\"Jiang\",\"suffix\":\"\"},{\"id\":618382264,\"identity\":\"35e96065-71bf-407e-a10a-0f56bd564be2\",\"order_by\":2,\"name\":\"Jiaqi Qi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"School of Electronic Science and Engineering, University of Electronic Science and Technology\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jiaqi\",\"middleName\":\"\",\"lastName\":\"Qi\",\"suffix\":\"\"},{\"id\":618382265,\"identity\":\"4b04fc1d-ecb8-408e-8ac0-454aff164b73\",\"order_by\":3,\"name\":\"Zhao Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"School of Electronic Science and Engineering, University of Electronic Science and Technology\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhao\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":618382267,\"identity\":\"fc4771f1-faab-40f7-9c35-daed9a48fa01\",\"order_by\":4,\"name\":\"Li Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Key Laboratory of Major Diseases in Children, Ministry of Education\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Li\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":618382269,\"identity\":\"3386008b-0c6e-46a7-888c-ca44905e6e49\",\"order_by\":5,\"name\":\"Xiaogang Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanxi Eye Hospital affiliated to Shanxi Medical University, Shanxi Intelligent Ophthalmic Engineering Research Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiaogang\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":618382271,\"identity\":\"beee7dad-1e3a-4cf6-8bc2-a49492338996\",\"order_by\":6,\"name\":\"Junhong Li\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACxgYGNhAtw8be2PjgQ4WEnDyxWnjYeA4fNpxxxsLYsIGwRRAtDBJpadK8bRWJDAcIqGeekXvswccdtTx8DDkGErzzJBIYG5gfPrqBz2Ez8tINZ545zsPGcMbAQHKbRB47A5uxcQ5eLTlmQPcc42Fj7DFIMNwmUczYwMMmTZwWZh6DA4lzJBIbDhCnpYaHjY0tseFgAzFaet6YSc5sAyrjYT7M2HBMwtiwmYBfDNtzzCQ+ttXJyc9/2P77Tw2Qwd788DFeLQ1g6jCSEDMe5SAATR51BJSNglEwCkbBiAYAJZ5HSs9GOb0AAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Shanxi Eye Hospital affiliated to Shanxi Medical University, Shanxi Intelligent Ophthalmic Engineering Research Center\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Junhong\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-03-05 10:24:31\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-9039006/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-9039006/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":106382545,\"identity\":\"c6e02952-ddf3-47ba-b621-bd4f07fc1a8a\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 05:28:38\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":18781,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eEarly Treatment Diabetic Retinopathy Study (ETDRS) grid applied to the 6 × 6 mm macular OCTA scan. The macula was divided into the central fovea (F), an inner ring (1–3 mm) subdivided into superior (IS), nasal (IN), inferior (II), and temporal (IT) sectors, and an outer ring (3–6 mm) subdivided into superior (OS), nasal (ON), inferior (OI), and temporal (OT) sectors. Quantitative analyses were performed within each sector and across the entire scan area.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/c7dcd5d34b6e4e6ccbbeea2e.png\"},{\"id\":106382546,\"identity\":\"e3dc682c-2aba-452b-bb84-3d00c88ada64\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 05:28:38\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":85887,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChanges in VVD in Supranormal and Conventional Dose Groups Following Horizontal Rectus Muscle Surgery. Blue indicates decrease, red indicates increase.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/18b5a4c5ba48e9585749550b.png\"},{\"id\":106404869,\"identity\":\"0e69d24c-a1e6-4e3e-b4da-d31b6689115d\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 09:17:16\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":86870,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChanges in VSD in Supranormal and Conventional Dose Groups Following Horizontal Rectus Muscle Surgery. Blue indicates decrease, red indicates increase.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/5c8ed3ab66de52e523b02502.png\"},{\"id\":106382549,\"identity\":\"ead08f53-4732-4d01-afb6-616c5a8b22a1\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 05:28:38\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":86780,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChanges in VDI in Supranormal and Conventional Dose Groups Following Horizontal Rectus Muscle Surgery. Blue indicates decrease, red indicates increase.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/1e0135315e13c6a6d3d0de06.png\"},{\"id\":106404663,\"identity\":\"047c0896-de59-47e2-a692-12c7ae5dc62d\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 09:16:29\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":775486,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eProposed model of dose-related macular microvascular responses after horizontal rectus muscle surgery. The schematic summarizes the observed time course (day 1, week 2, week 6) and a putative mechanism.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/414d471237d00d0d74e11196.png\"},{\"id\":106993855,\"identity\":\"b6976ba8-896a-4b26-95bb-6cf62e8bc561\",\"added_by\":\"auto\",\"created_at\":\"2026-04-15 14:59:04\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1494712,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/f12c583c-2ce2-4d69-89c7-dfc038d3825d.pdf\"},{\"id\":106382544,\"identity\":\"e7779329-1113-425f-bfae-aeb4e563338c\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 05:28:38\",\"extension\":\"docx\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":139372,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SupplementaryTable.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/374d126d77bd5d90d6333a7e.docx\"},{\"id\":106404639,\"identity\":\"aa917db2-aaf0-4e24-939b-e21a998e0a13\",\"added_by\":\"auto\",\"created_at\":\"2026-04-08 09:16:26\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":762442,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SupplementaryFigure.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9039006/v1/5f6ca83723ab8052d3c84064.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Dose-Related, Layer-Specific Alterations in Macular Microcirculation Following Horizontal Rectus Muscle Surgery: A Three-Dimensional OCT Angiography Study\",\"fulltext\":[{\"header\":\"Key Message\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eWhat is known\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull;\\u0026nbsp;Postoperative alterations in ocular blood flow have been reported after strabismus surgery, but macular microvascular findings remain heterogeneous across studies.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eWhat this study adds\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull;\\u0026nbsp;Three-dimensional OCTA demonstrates dose-related, layer-specific changes in macular microcirculation following horizontal rectus muscle surgery.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull;\\u0026nbsp;Higher cumulative surgical dose is associated with more pronounced early alterations in deep capillary plexus perfusion metrics.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Regional heterogeneity suggests sector-specific dose sensitivity within the macula.\\u003c/p\\u003e\"},{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eStrabismus surgery is routinely performed to correct ocular misalignment and restore binocular vision. However, horizontal rectus muscle procedures inevitably disrupt anterior ciliary artery flow and trigger postoperative inflammatory responses. These perioperative perturbations may alter ocular hemodynamics, including retinal and macular microcirculation.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e Early Doppler-based hemodynamic assessments showed transient postoperative changes in bulk blood flow of larger retrobulbar vessels such as the ophthalmic artery, typically returning to baseline within days to weeks, but provided limited insight into capillary-level responses within the macula.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eThe advent of optical coherence tomography angiography (OCTA) has enabled noninvasive, in vivo visualization of the macular microvasculature. However, previous OCTA studies have reported heterogeneous postoperative patterns, with variability in the direction and timing of changes, as well as inconsistencies across macular subfields and vascular plexuses.\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR5\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]\\u003c/sup\\u003e These discrepancies may partly reflect differences in follow-up schedules and the predominant use of two-dimensional vessel-density summaries. In contrast, our three-dimensional OCTA (3D-OCTA) approach leverages the full angiographic volume to quantify vessel volume density, vessel skeleton density, and caliber-sensitive changes, enabling a more comprehensive assessment of postoperative microvascular alterations. Importantly, the potential influence of surgical dose, defined as the cumulative extent of muscle recession and/or resection, on postoperative microcirculatory responses has received little attention. Whether larger surgical doses induce greater microvascular impairment or alter recovery trajectories remains unclear.\\u003c/p\\u003e \\u003cp\\u003eThe macular microvasculature is highly compartmentalized, with pronounced layer-specific and regional heterogeneity. The superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) differ in anatomical configuration, perfusion pressure, and regulatory capacity, suggesting that each plexus may respond differently to surgical stress.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]\\u003c/sup\\u003e Three-dimensional OCTA (3D-OCTA) enables quantitative assessment of microvascular architecture beyond conventional two-dimensional metrics by incorporating vessel volume, skeletonized length, and caliber, thereby providing a more comprehensive characterization of postoperative vascular remodeling.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eIn this study, we used 3D-OCTA to longitudinally characterize layer- and region-specific changes in macular microcirculation after horizontal rectus muscle surgery. Using generalized estimating equation (GEE) modeling, we compared postoperative trajectories across eyes stratified by cumulative surgical dose and evaluated whether microvascular responses varied with surgical dose.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eStudy Design and Participants\\u003c/p\\u003e \\u003cp\\u003eThis prospective study recruited patients undergoing horizontal rectus muscle surgery at Shanxi Eye Hospital from April to August 2024, with \\u0026ge;\\u0026thinsp;6 weeks of postoperative follow-up. The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shanxi Eye Hospital affiliated with Shanxi Medical University (approval No. SXYYLL-KSSC051). Exclusion criteria included prior ocular surgery; best-corrected visual acuity\\u0026thinsp;\\u0026lt;\\u0026thinsp;1.0; spherical equivalent (SE)\\u0026thinsp;\\u0026le;\\u0026thinsp;\\u0026minus;\\u0026thinsp;6.0 diopters (D); systemic vasculopathy, such as diabetes or hypertension; developmental or neurologic disorders; poor OCTA image quality or artifacts; and concurrent oblique muscle surgery.\\u003c/p\\u003e \\u003cp\\u003eAll patients underwent standard preoperative ophthalmic examinations, including visual acuity, refraction, slit-lamp biomicroscopy, funduscopy, tonometry, motility assessment, and strabismus angle measurement at near and distance.\\u003c/p\\u003e \\u003cp\\u003eSurgical Procedures\\u003c/p\\u003e \\u003cp\\u003eAll procedures were performed under microscopy by a single experienced surgeon. Techniques included medial or lateral rectus recession, resection, or combined recession-resection, tailored to the magnitude of the deviation. Medial rectus adjustments were \\u0026le;\\u0026thinsp;8 mm; lateral rectus adjustments were \\u0026le;\\u0026thinsp;10 mm. Eyes were grouped by cumulative dose for the supranormal dose group (\\u0026ge;\\u0026thinsp;14 mm) or the conventional dose group (\\u0026lt;\\u0026thinsp;14 mm).\\u003c/p\\u003e \\u003cp\\u003eOCTA Acquisition and Segmentation\\u003c/p\\u003e \\u003cp\\u003eA trained operator acquired 6\\u0026times;6-mm macular OCTA scans (SPECTRALIS II OCT system, Heidelberg Engineering, Heidelberg, Germany) preoperatively and on postoperative day 1, week 2, and week 6 under controlled illumination. The macula was segmented according to the Early Treatment Diabetic Retinopathy Study (ETDRS) standard grid into the central fovea (F); an inner ring subdivided into superior, nasal, inferior, and temporal sectors (IS, IN, II, IT); and an outer ring subdivided into superior, nasal, inferior, and temporal sectors (OS, ON, OI, OT) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Additionally, metrics were computed for the entire 6 \\u0026times; 6 mm macular scan area. Retinal vascular plexuses were segmented into the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) using the standardized boundaries proposed by Campbell et al.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e In brief, the superficial vascular plexus (SVP) was defined within the more internal portion of the ganglion cell complex, the intermediate capillary plexus (ICP) spanned the remaining outer one-fifth of the ganglion cell complex together with the inner half of the inner nuclear layer (INL), and the deep capillary plexus (DCP) extended from the outer half of the INL through the full thickness of the outer plexiform layer (OPL). Quantitative analyses were performed for SVP, ICP, and DCP in each ETDRS sector as well as in the whole-scan region.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eThree-Dimensional Vascular Metrics\\u003c/p\\u003e \\u003cp\\u003eThree-dimensional vascular parameters were extracted from the reconstructed OCTA volume within each analyzed sector and plexus. Vessel volume density (VVD) was defined as the ratio of retinal vessel volume to the total retinal volume in the measured region, capturing both vessel length and caliber and providing an estimate of actual vessel density. Vessel skeleton density (VSD) was defined as the total vessel length per unit tissue volume, reflecting vessel density primarily based on vessel length. Vessel diameter index (VDI) was calculated as the ratio of total vessel volume to total vessel length (equivalently, VVD/VSD), reflecting the mean vessel caliber in the region and being sensitive to vessel dilation on OCTA. To minimize ocular magnification effects related to axial length, the nominal OCTA scan size was rescaled using the Littmann approach together with the modified Bennett formula. For the Heidelberg platform, the default axial length was set to 24.385 mm. An area-based correction factor was computed as \\u003cspan class=\\\"InlineEquation\\\"\\u003e\\u003cspan class=\\\"mathinline\\\"\\u003e\\\\({\\\\left(\\\\frac{A{L}_{actual}-1.82}{A{L}_{default}-1.82}\\\\right)}^{2}\\\\)\\u003c/span\\u003e\\u003c/span\\u003e, and the corresponding linear scaling factor was derived as \\u003cspan class=\\\"InlineEquation\\\"\\u003e\\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\frac{A{L}_{actual}-1.82}{A{L}_{default}-1.82}\\\\)\\u003c/span\\u003e\\u003c/span\\u003e. The ETDRS sector boundaries and whole-scan dimensions were adjusted according to this scaling factor before quantitative analysis.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eStatistical analyses were performed in SPSS 28.0. Normality was assessed using the Shapiro\\u0026ndash;Wilk test. Baseline characteristics were compared using independent-samples t-tests and χ\\u0026sup2; tests. Within each dose group, longitudinal changes in VVD, VSD, and VDI were evaluated using GEE with time as the repeated factor and age as a covariate. An independent working correlation structure was applied to account for repeated measurements and potential inter-eye correlation. Post hoc simple contrasts comparing each follow-up visit to baseline were adjusted using the Holm method. Spearman rank correlation analysis was performed to assess the relationship between surgical dose and postoperative changes in macular microcirculation. Time points were classified as postoperative day 1, 2 weeks, and 6 weeks, with Δ values representing changes relative to baseline. A two-tailed P-value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered statistically significant.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eClinical Characteristics in this study\\u003c/p\\u003e \\u003cp\\u003eBaseline demographic and clinical characteristics were similar between the supranormal-dose (\\u0026ge;\\u0026thinsp;14 mm) and conventional-dose (\\u0026lt;\\u0026thinsp;14 mm) groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). There were no statistically significant between-group differences in sex, age, or spherical equivalent refractive error (all P\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBaseline demographic and clinical characteristics of the study eyes.\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eGender\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eSupranormal dose (\\u0026ge;\\u0026thinsp;14 mm) group\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;15\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eConventional dose (\\u0026lt;\\u0026thinsp;14 mm) group\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;25\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cspan class=\\\"InlineEquation\\\"\\u003e\\u003cspan class=\\\"mathinline\\\"\\u003e\\\\({{\\\\chi}}^{2}/t\\\\)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cspan class=\\\"InlineEquation\\\"\\u003e\\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(P\\\\)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.444\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.505\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8(53.33)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16(64.00)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFemale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e7(46.67)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e9(36.00)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge (y)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e22.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.96\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e20.92\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.88\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.623\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.537\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSpherical equivalent (D)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e-2.08\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.29\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e-2.99\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.29\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.213\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.233\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eData are presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD or n (%). P values were obtained from independent-samples t tests or χ\\u0026sup2; tests, as appropriate.\\u003c/p\\u003e \\u003cp\\u003eSD, standard deviation\\u003c/p\\u003e \\u003cp\\u003eD, diopters.\\u003c/p\\u003e \\u003cp\\u003eLongitudinal Changes in VVD\\u003c/p\\u003e \\u003cp\\u003eIn the supranormal-dose group, GEE showed significant early decreases in DCP VVD on postoperative day 1 in the outer superior and outer temporal sectors, as well as in the whole-scan region, indicating early deep-layer hypoperfusion. At 2 weeks, VVD increased transiently in the ICP and SVP, predominantly in the superior and nasal sectors of both the inner and outer rings, with a concurrent increase in the whole-scan region. By 6 weeks, a residual reduction in DCP VVD persisted in the outer temporal sector and remained detectable at the whole-scan level. The conventional-dose group showed no early reductions in VVD. At 2 weeks, VVD increases were mainly concentrated in the inferior-related sectors; meanwhile, whole-scan VVD increased across the DCP, ICP, and SVP layers. By 6 weeks, VVD generally trended toward stabilization; however, several DCP sectors remained elevated in the conventional-dose group (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eLongitudinal Changes in VSD\\u003c/p\\u003e \\u003cp\\u003eVSD trajectories largely paralleled those of VVD. Supranormal-dose eyes exhibited early reductions in deep-layer VSD in the outer superior and outer temporal sectors, as well as in the whole-scan region on day 1. This was followed by transient increases at 2 weeks, primarily in the ICP across multiple sectors, along with additional SVP increases. No significant differences from baseline were detected at 6 weeks. Conventional-dose eyes showed delayed increases in VSD at 2 weeks, with DCP VSD remaining elevated in selected outer-ring sectors at 6 weeks (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eLongitudinal Changes in VDI\\u003c/p\\u003e \\u003cp\\u003eIn the supranormal-dose group, VDI decreased on postoperative day 1 mainly in the ICP, with a concurrent whole-scan decrease in the DCP. At 6 weeks, a residual reduction persisted in the inner inferior sector, accompanied by an increase in the foveal DCP. In the conventional-dose group, VDI increased predominantly in the DCP from 2 weeks through 6 weeks across multiple regions, including the whole-scan area (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eDose-Response Correlation Analysis\\u003c/p\\u003e \\u003cp\\u003eSpearman analyses revealed region- and layer-specific dose\\u0026ndash;response relationships. Higher surgical doses correlated negatively with ΔVVD and ΔVSD in predominantly nasal and superior sectors, indicating that larger doses were associated with smaller compensatory increases or greater postoperative loss (Supplementary Figure \\u003cspan refid=\\\"MOESM1\\\" class=\\\"InternalRef\\\"\\u003eS1\\u003c/span\\u003e and S2). In contrast, positive correlations were observed for ΔVDI at 2 weeks in selected regions, suggesting greater caliber increases with higher doses. At 6 weeks, negative correlations between dose and foveal DCP ΔVDI suggested protracted recovery in higher-dose cases (Supplementary Figure S3). In the scatterplots, linear fits are shown for visualization only. The full Spearman correlation results for each region and timepoint are provided in Supplementary Table S4, S5 and S6.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThis study suggests dose-related changes in macular microcirculation after horizontal rectus muscle surgery. Supranormal-dose eyes showed more prominent microvascular disturbance, with a greater tendency toward early deep-layer reductions in VVD and VSD and clearer dose\\u0026ndash;response patterns in selected sectors and time points. Specifically, higher surgical doses were associated with more pronounced postoperative decreases in VVD or VSD or less evident compensatory increases. In contrast, changes in the conventional-dose group were predominantly delayed and compensatory and tended to recover over follow-up. Overall, these findings suggest that macular microcirculation exhibits dose sensitivity and may indicate a shift from compensatory adaptation toward microvascular injury at higher surgical doses. Prior OCTA studies in other retinal conditions have demonstrated that capillary loss is associated with poorer visual function.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e Therefore, the more prominent deep-layer abnormalities observed in supranormal-dose eyes may indicate a prolonged functional recovery period, supporting closer OCTA monitoring in higher-dose cases.\\u003c/p\\u003e \\u003cp\\u003eAcross analyses, the DCP appeared to be the most responsive and vulnerable plexus after surgery. In the supranormal-dose group, early reductions were most consistently observed in DCP VVD and VSD, especially in the outer-ring sectors and at the whole-scan level. In contrast, the SVP and ICP showed relative preservation, with transient compensatory increases at later visits. This layer-specific pattern highlights the DCP as a key site of postoperative microvascular stress and suggests that the deeper retinal circulation is especially sensitive to surgical perturbation.\\u003c/p\\u003e \\u003cp\\u003eLongitudinal evaluation suggested dose-related differences in postoperative microvascular patterns. Eyes receiving supranormal doses tended to show earlier deep-layer hypoperfusion, less prominent compensatory responses in some sectors, and residual abnormalities in selected deep-layer regions by 6 weeks. By comparison, conventional-dose eyes more often exhibited delayed compensatory hyperperfusion and vasodilation, with many parameters trending toward stabilization over follow-up, although some sector- and layer-specific changes persisted. Collectively, these observations support a dose-sensitive microvascular response and suggest that higher surgical doses may shift the balance toward greater microvascular stress and slower recovery.\\u003c/p\\u003e \\u003cp\\u003eThe underlying mechanisms may relate to intraoperative disturbance of the anterior ciliary circulation and adjacent tissues, which primarily supply the anterior segment and influence posterior segment perfusion through collateral pathways.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]\\u003c/sup\\u003e In supranormal-dose procedures, extensive vascular transection and tissue trauma may overwhelm compensatory collateral capacity, resulting in downstream macular hypoperfusion. The apparent susceptibility of the DCP may reflect both its anatomical position and limited hemodynamic reserve. It is organized as a predominantly planar capillary network with relatively limited anastomotic and collateral redundancy. Additionally, DCP flow is thought to operate under lower perfusion pressure with a narrower autoregulatory reserve, which may render it more sensitive to ischemic stress (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e).\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR15 CR16\\\" citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eOverall, these findings indicate region-specific dose sensitivity within the macula: some sectors appear more prone to persistent alterations, while others may show recovery through adaptive remodeling. Notably, the nasal and superior macular sectors exhibited significant negative dose\\u0026ndash;response relationships in perfusion metrics at specific time points, indicating greater sensitivity to surgical trauma. This sensitivity may be related to the asymmetric macular microvascular architecture and limited collateral support in these regions.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]\\u003c/sup\\u003e In contrast, the temporal deep-layer measures showed positive dose\\u0026ndash;response relationships for ΔVVD and ΔVDI at postoperative week 2, consistent with increased density and caliber associated with higher doses. Despite these general patterns, substantial interindividual variability was observed during these adaptive or recovery processes.\\u003c/p\\u003e \\u003cp\\u003eFrom a clinical perspective, these findings inform surgical decision-making. In patients with preexisting microvascular compromises, such as diabetes mellitus, hypertension, or other conditions that impair microcirculatory regulation, vascular reserve may be diminished. In such individuals, supranormal-dose strabismus surgery may increase the likelihood of prolonged deep-layer perfusion alterations, which could be clinically significant even in the absence of overt complications. Therefore, careful consideration of surgical dose, alternative techniques, or staged strategies may be warranted in high-risk populations.\\u003c/p\\u003e \\u003cp\\u003eStrabismus often requires reoperation, with timing decisions typically guided by ocular alignment, muscle adaptation, and scar maturation; however, retinal microcirculation is rarely considered. Prior studies have reported heterogeneous postoperative hemodynamic time courses using different modalities.\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR20\\\" citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]\\u003c/sup\\u003e Our results suggest that compensatory microvascular responses are most prominent around 2 weeks postoperatively, with many regions approaching an early stabilization phase by approximately 6 weeks, particularly following conventional-dose surgery. Notably, certain deep-layer alterations after supranormal-dose procedures persisted at 6 weeks, indicating slower vascular recovery in eyes receiving higher doses. Although routine reoperation is generally scheduled several months later, these findings provide a physiological context for postoperative monitoring and may be especially relevant when early re-intervention is unavoidable, underscoring the need for caution during the first 6 weeks.\\u003c/p\\u003e \\u003cp\\u003eThese results also help refine postoperative monitoring. OCTA at postoperative day 1 can capture acute perfusion disturbances, an intermediate assessment around 2 weeks can characterize compensatory peaks, and a follow-up around 6 weeks can evaluate recovery trends or residual deficits. This tiered schedule may be particularly useful for high-dose cases or patients with vascular comorbidities.\\u003c/p\\u003e \\u003cp\\u003eSeveral limitations warrant acknowledgment. First, the sample size was moderate, which may have limited more detailed subgroup analyses. Second, the 6-week follow-up captured acute and subacute dynamics but may have overlooked longer-term remodeling or sequelae. Third, analyses were performed at the eye level, and the inclusion of some bilateral cases may have introduced inter-eye non-independence. Finally, our focus on macular microcirculation precluded evaluation of anterior segment or choroidal perfusion. Future studies with larger cohorts, extended longitudinal follow-up, and multimodal imaging, including anterior segment OCTA and dedicated choroidal flow assessment, are warranted to better characterize comprehensive ocular hemodynamic responses to strabismus surgery.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eXiyu Zhao, Shanxi Provincial Department of Education, Postgraduate Practical Innovation Project, 2024SJ167\\u003c/p\\u003e\\n\\u003cp\\u003eJunhong Li, Shanxi Provincial Department of Science and Technology, Central Guiding Local Technology Development Introduction In the era of rapid technological advancement of Shanxi Provincial department of Science and Technology, YDZJSX2024B013\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eHuman Ethics and Consent to Participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was approved by the Ethics Committee of Shanxi Eye Hospital affiliated with Shanxi Medical University (Approval No. SXYYLL-KSSC051) and adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal guardians.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eClinical Trial Registration\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eClinical trial number: Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contribution\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eX.Y.Z. collected the data and drafted the main manuscript.J.J.J. contributed to study conception and manuscript writing. J.Q.Q. performed image processing. Z.W. supervised the image analysis and provided methodological guidance. L.L. provided academic supervision and critical input throughout the study. X.G.W. facilitated data acquisition and provided academic supervision and critical input throughout the studythe clinical setting for patient recruitment. J.H.L. contributed to the study design oversight, provided senior academic guidance, and facilitated the clinical setting for patient recruitment.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData Availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and institutional restrictions but are available from the corresponding author on reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eHuang YT, Lin SC, Huang LY, et al. Incidence, Risk Factors and Management of Postoperative Complications in Horizontal Strabismus Surgery. Semin Ophthalmol. 2024;39(2):143\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePelit A, Barut\\u0026ccedil;u O, Oto S, Aydin P. Investigation of hemodynamic changes after strabismus surgery using color Doppler imaging. J AAPOS. 2002;6(4):224\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLee NH, Lee SN. Investigation of hemodynamic changes in the ophthalmic artery using color Doppler imaging after strabismus surgery. Korean J Ophthalmol. 2005;19(3):208\\u0026ndash;12.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eVagge A, Nucci P, Ferro Desideri L et al. Evaluation of macular vessel density changes after strabismus surgery using optical coherence tomography angiography. J AAPOS. 2022. 26(2): 71.e1-71.e4.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eInal A, Yilmaz I, Ocak OB, et al. Optical Coherence Tomography Angiography: Are There Any Changes in Measurements After Strabismus Surgery. J Pediatr Ophthalmol Strabismus. 2019;56(2):95\\u0026ndash;100.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHuseyinhan Z, Ozcaliskan S, Gurez C, Artunay O. Retinal and choroidal microvasculature is altered after strabismus surgery. Eur J Ophthalmol. 2022: 11206721221137156.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChandrasekera E, An D, McAllister IL, Yu DY, Balaratnasingam C. Three-Dimensional Microscopy Demonstrates Series and Parallel Organization of Human Peripapillary Capillary Plexuses. Invest Ophthalmol Vis Sci. 2018;59(11):4327\\u0026ndash;44.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLiu Y, Tang Z, Li C, et al. AI-based 3D analysis of retinal vasculature associated with retinal diseases using OCT angiography. Biomed Opt Express. 2024;15(11):6416\\u0026ndash;32.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCampbell JP, Zhang M, Hwang TS, et al. Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography. Sci Rep. 2017;7:42201.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSampson DM, Gong P, An D, et al. Axial Length Variation Impacts on Superficial Retinal Vessel Density and Foveal Avascular Zone Area Measurements Using Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2017;58(7):3065\\u0026ndash;72.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTian X, Liu Y, Ning X, et al. 3D-OCTA Evaluation of Retinal Microcirculation Abnormalities in the Macular Region of Eyes With Anisometropic Amblyopia. Transl Vis Sci Technol. 2025;14(10):4.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFeng J, Yang X, Xu M, et al. Association of Microvasculature and Macular Sensitivity in Idiopathic Macular Epiretinal Membrane: Using OCT Angiography and Microperimetry. Front Med (Lausanne). 2021;8:655013.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOlver JM, Lee JP. The effects of strabismus surgery on anterior segment circulation. Eye (Lond). 1989. 3 (Pt 3): 318\\u0026thinsp;\\u0026ndash;\\u0026thinsp;26.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLavia C, Bonnin S, Maule M, Erginay A, Tadayoni R, Gaudric A. VESSEL DENSITY OF SUPERFICIAL, INTERMEDIATE, AND DEEP CAPILLARY PLEXUSES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina. 2019;39(2):247\\u0026ndash;58.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBalaratnasingam C, An D, Hein M, Yu P, Yu DY. Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy. Prog Retin Eye Res. 2023;94:101134.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLavia C, Mec\\u0026ecirc; P, Nassisi M, et al. Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography. Sci Rep. 2020;10(1):1474.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFouquet S, Vacca O, Sennlaub F, Paques M. The 3D Retinal Capillary Circulation in Pigs Reveals a Predominant Serial Organization. Invest Ophthalmol Vis Sci. 2017;58(13):5754\\u0026ndash;63.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eYu PK, Mammo Z, Balaratnasingam C, Yu DY. Quantitative Study of the Macular Microvasculature in Human Donor Eyes. Invest Ophthalmol Vis Sci. 2018;59(1):108\\u0026ndash;16.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eG\\u0026uuml;l C, Erşan H, Karapapak M, G\\u0026uuml;ven D. Optical Coherence Tomography Angiography Evaluation of Retinal and Choroidal Microvascular Morphological Changes Following Strabismus Surgery. J Pediatr Ophthalmol Strabismus. 2024;61(6):397\\u0026ndash;403.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEmekli DT, Aydamirov AS. Investigation of the effects of single and two-muscle horizontal rectus surgeries on macular microvasculature. Graefes Arch Clin Exp Ophthalmol. 2025;263(1):217\\u0026ndash;23.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eYasuda S, Takai Y, Yasuda Y, et al. Quantitative Evaluation of Changes in Retinal and Choroidal Blood Flow Following Strabismus Surgery. Transl Vis Sci Technol. 2025;14(3):12.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"boph\",\"sideBox\":\"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/boph\",\"title\":\"BMC Ophthalmology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Strabismus surgery, Optical coherence tomography angiography, Macular microcirculation\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-9039006/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-9039006/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003ePurpose: \\u003c/strong\\u003eTo investigate dose-related, layer-specific, and regional changes in macular microcirculation after horizontal rectus muscle surgery using three-dimensional optical coherence tomography angiography (3D-OCTA).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003eThis prospective observational study included 40 eyes from 30 patients. Eyes were grouped by cumulative surgical dose (supranormal ≥14 mm, n=15; conventional \\u0026lt;14 mm, n=25). Macular 6×6-mm OCTA was obtained preoperatively and at postoperative day 1, week 2, and week 6. Three-dimensional vessel volume density (VVD), vessel skeleton density (VSD), and vessel diameter index (VDI) were quantified in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) across ETDRS subfields and a whole-scan region. Longitudinal changes were assessed using generalized estimating equations with Holm-adjusted contrasts versus baseline, and dose–response relationships using Spearman correlation.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eSupranormal-dose eyes showed early reductions in VVD and VSD of the DCP on day 1, most evident in outer-ring sectors and the whole-scan region. Increases in both the SVP and ICP emerged at week 2, while residual deep-layer abnormalities persisted in selected sectors at week 6. Conventional-dose eyes showed no early decline but demonstrated compensatory increases at week 2 and sustained DCP dilation through week 6. Higher dose correlated with smaller ΔVVD and ΔVSD responses in nasal and superior sectors and greater temporal deep-layer ΔVDI.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions: \\u003c/strong\\u003eHorizontal rectus muscle surgery induces dose-sensitive macular microvascular alterations, with higher doses preferentially affecting the DCP and showing slower recovery in selected regions. 3D-OCTA enables sensitive detection of these changes and may assist in surgical planning and postoperative monitoring.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Dose-Related, Layer-Specific Alterations in Macular Microcirculation Following Horizontal Rectus Muscle Surgery: A Three-Dimensional OCT Angiography Study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-04-08 05:28:30\",\"doi\":\"10.21203/rs.3.rs-9039006/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-04-02T04:26:20+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2026-03-07T07:15:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-03-06T05:07:53+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-03-06T05:07:53+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Ophthalmology\",\"date\":\"2026-03-05T10:11:35+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"boph\",\"sideBox\":\"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/boph\",\"title\":\"BMC Ophthalmology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"be7c72e6-232f-4096-a53e-b60d16f6bf3c\",\"owner\":[],\"postedDate\":\"April 8th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-04-08T05:28:30+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-04-08 05:28:30\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-9039006\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-9039006\",\"identity\":\"rs-9039006\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}