OCT Angiography Parameters in Nasal Polyposis Associated with Chronic Rhinosinusitis

OCT Angiography Parameters in Nasal Polyposis Associated with Chronic Rhinosinusitis | 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 OCT Angiography Parameters in Nasal Polyposis Associated with Chronic Rhinosinusitis Tülin Öğreden, Gülistan Oyur, Özgü Canbolat, Şahin Öğreden This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7032382/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract PURPOSE This study aimed to evaluate optical coherence tomography angiography (OCTA) parameters in cases of chronic rhinosinusitis with nasal polyposis (CRSwNP), a common cause of chronic airway obstruction. These parameters were compared with those of healthy individuals. METHODS In this prospective study, 29 eyes of 29 participants with CRSwNP and 30 eyes of 30 individuals in the healthy control group were evaluated. Cases diagnosed with CRSwNP were defined as group 1, and the control group as group 2. Nasal polyps were documented and graded using nasal endoscopy. A complete ophthalmic examination and OCTA analysis were performed. Retinal vascular density (VD) in four quadrants of both the superficial and deep capillary plexuses were analyzed. Foveal avascular zone (FAZ) area, retinal nerve fiber layer (RNFL), and vessel diameter index (VDI) were measured and compared. RESULTS Retinal VD in the superficial plexus showed a significant difference between Group 1 and Group 2 only in the nasal quadrant (p=0.046). In the deep capillary plexus, differences were statistically significant in all quadrants (nasal, temporal, superior, and inferior), with lower vascular density in the CRSwNP group (p=0.008, p=0.037, p=0.011, and p=0.001, respectively). In Group 1, FAZ areas were 0.390±0.81 mm 2 and 0.395±0.96 mm 2 in the superficial and deep plexuses, respectively. In Group 2, superficial and deep FAZ areas were 0.337±0.12 mm 2 and 0.467±0.14 mm 2 , respectively. The difference in FAZ area in the superficial plexus was not statistically significant, but the difference in the deep plexus was (p=0.062 and p=0.022, respectively). VDI was slightly higher in Group 1 than in Group 2, but the difference was not statistically significant in either the superficial or deep plexus (p=0.259 and p=0.200, respectively). The average macular RNFL thickness was 110.31±10.48 µm in Group1 and 93.22±11.50 µm in Group2, with the difference being statistically significant (p=0.007). CONCLUSION CRSwNP is an upper respiratory tract obstruction that can lead to hypoxia, increased small vessel resistance, dysregulation of nocturnal blood pressure, and alterations in perfusion pressure. The severity of nasal polyposis has been shown to significantly increase oxidative stress. CRSwNP may also result in differences in some OCTA parameters when compared to healthy individuals. To the best of our knowledge, this is the first study to evaluate OCTA findings in patients with CRSwNP. Our findings suggest that repeated hypoxic cycles may affect OCTA parameters, particularly in the outer retinal layers and the RNFL. Optical coherence tomography angiography(OCTA) nasal polyposis chronic rhinosinusitis Figures Figure 1 INTRODUCTION Chronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and the linings of the nasal passages that persists for 12 weeks or longer. It is a relatively common condition affecting all age groups. CRS is classified into three types: CRS with nasal polyposis (CRSwNP), which accounts for 20 to 33% of cases; allergic fungal rhinosinusitis (AFRS); and CRS without nasal polyposis (CRSsNP)[1]. CRSwNP is among the diseases that impair nasal airway flow and tissue oxygenation by causing obstruction. Symptoms of CRSwNP include anosmia, facial pressure, nasal drainage, and nasal obstruction. Chronic obstruction may result in hypoxia and persistently low oxygen saturation. This contributes to increased vasoactive responses, systemic hypertension, and loss of the physiological nocturnal decrease in blood pressure[2]. Prior studies have demonstrated changes in oxygen saturation[3] and elevated serum inflammatory markers in patients with CRSwNP [4]. The retina is one of the most metabolically active tissues and has the highest oxygen demand per unit area in the body. The vascular system that nourishes the retina is directly influenced by blood oxygen levels. While the retina can autoregulate in response to acute changes in saturation, repeated and prolonged hypoxic attacks may result in permanent structural changes in the retinal vasculature[5]. Retinal tissue alterations can be assessed quantitatively and qualitatively using advanced imaging technologies. Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging modality that provides detailed visualization of blood flow and the retinal-choroidal capillary network [6]. Its primary applications are in retinal, choroidal, anterior segment, and optic nerve disorders [7]. OCTA is also increasingly used to assess the ocular effects of systemic disorders, even in the absence of primary ocular pathology [8]. Measuring retinal microcirculation using OCTA may offer valuable insights into the preclinical hemodynamic of CRSwNP on the eye. Previous studies have shown that retinal nerve fiber layer (RNFL) thickness and retinal-choroidal vascular structures may be altered in systematic conditions such as obstructive sleep apnea syndrome, coronary artery disease, and carotid artery stenosis, as demonstrated by OCTA [8,9,10,11]. However, to our knowledge, no previous studies have investigated the impact of CRSwNP on the retinal capillary network by OCTA imaging. METHODS Participants and Data Collection This prospective, cross-sectional study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Başakşehir Çam and Sakura City City Hospital ( Approval No. 2022.04.113). Informed consent was obtained from all participants included in the study. According to the criteria outlined in the European Position Paper on Rhinosinusitis and Nasal Polyps 2020, the diagnosis of chronic rhinosinusitis (CRS) was based on the presence of at least two of the four cardinal symptoms: anterior and/or posterior mucopurulent nasal drainage, nasal obstruction/nasal blockage/congestion, facial pain, pressure, and/or fullness, and reduction or loss of sense of smell. Nasal polyps were confirmed by rhinoscopy (with decongestion) and nasal endoscopy, through direct visualization of the nasal cavity. The severity of nasal polyps was graded on a scale from 0 to 4. Patients with CRSwNP and healthy volunteers (control group) were followed in the Otolaryngology and Ophthalmology Departments of Başakşehir Çam and Sakura City Hospital between April 2022 and July 2023. A total of 29 eyes of 29 CRSwNP participants and 30 eyes of 30 individuals in the healthy control group were included. All participants underwent best-corrected visual acuity (BCVA) assessment using Snellen chart, slit-lamp biomicroscopy, tonometry, and OCTA imaging. One eye (left) of each participant was included in the analysis. OCTA imaging was performed using 6 mm × 6 mm macular scan. The following parameters were analyzed : retinal vascular density (VD) in four quadrants (both superficial and deep capillary plexuses), vessel diameter index (VDI), and foveal avascular zone (FAZ) area. Inclusion criteria were as follows: patients with nasal polyps graded ≥3 and significant airway obstruction were included in the study group. Only patients with a confirmed CRSwNP diagnosis of at least 2 years were enrolled. Pulse oximetry was performed prior to the ophthalmologic examination, and only cases with oxygen saturation levels above 90% were considered eligible. All participants in the study group had a best-corrected visual acuity (BCVA) of 20/20 and no additional respiratory or ocular pathology. Exclusion criteria were as follows: presence of refractive errors affecting visual acuity; corneal, lens or vitreous pathologies; retinal vascular diseases, dystrophies, or any form of macular degeneration; ocular surgery within the past six months; ocular ischemic syndrome; pulmonary diseases affecting blood oxygen levels (e.g., chronic obstructive pulmonary disease); history of treated or untreated airway stenosis; systemic vascular diseases such as diabetes mellitus and hypertension; dyslipidemia; obstructive sleep apnea syndrome; and a body mass index greater than 25. Age- and sex-matched controls were included in this study. The control group consisted of volunteers visiting the eye clinic who had at least 20/20 BCVA, no systemic or ocular pathology, and oxygen saturation >90% as measured by pulse oximetry. The same exclusion criteria were applied to the control group. OCTA Imaging Protocol: All OCTA imaging was performed by an experienced technician who was blinded to the clinical status of the participants. Imaging was obtained using the Topcon DRI OCT Triton Swept Source-device (Topcon Corporation, Tokyo, Japan), which operates at an A-scan repetition rate of 100.000 kHz, with a 1050 nm wavelength and a tissue depth resolution of 2 µm. The device has a full width at half-maximum of 100 nm and a lateral resolution on the retinal surface of 15 µm. Before imaging, each participant received pupil dilation with 0.5% tropicamide and 2.5% phenylephrine. A 6 × 6 mm scanning area centered on the fovea was used for image acquisition. Each scan was repeated three times during acquisition. The macular area was automatically divided into four equal quadrants (temporal, nasal, inferior, and superior) and a central circular zone (Figure 1). The inner retinal lamina was defined as the area between the internal limiting membrane and the outer plexiform layer (OPL), and the outer retina as the area between the Bruch’s membrane and the inner nuclear layer/OPL junction. The superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed using the device’s built-in default segmentation boundaries. Manual segmentation was performed in cases with evident segmentation artifacts. We evaluated the following quantitative parameters: foveal avascular zone (FAZ), vessel density (VD), and vessel diameter index (VDI). The FAZ area was automatically measured using the device’s embedded FAZ assessment tool. Vascular density(VD) was defined as the percentage of the area occupied by large vessels and microvasculature. The vessel diameter index (VDI) was calculated as the ratio of the total vessel area to vessel length. In addition to these parameters, mean macular thickness and retinal nerve fiber layer (RNFL) thickness were measured using the optical coherence tomography (OCT) mode of the device. Low-quality scans were excluded and repeated until a satisfactory signal strength index was achieved. OCTA images containing motion artifacts or flashing artifacts that could affect analysis were also excluded. Figure1: OCTA en face İmage showing four equal quadrants (temporal, nasal, inferior, and superior) and central area. Statistical Analysis Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), Version 22.0 for Windows (SPSS Inc., Chicago, IL, USA). Descriptive statistics are presented as mean ± standard deviation, along with minimum and maximum values for numerical variables. Pearson’s chi-square test and the one-sample chi-square test were used for categorical variables. For comparisons between groups, the independent sample t-test was used for normally distributed data, while Mann-Whitney U test was applied for non-normally distributed data. A p-value of <0.05 was considered statistically significant. RESULTS Cases diagnosed with CRSwNP were defined as Group 1, and the control group as Group 2. Group 1 consisted of 29 patients, and Group 2 included 30 individuals. Data from one eye per participant were analyzed. The mean age of Group 1 (52.0% female) was 34.17 ± 9.9 years, and the mean age of Group 2 (50% female) was 32.40 ± 10.28 years. Descriptive data on age, gender, Intraocular pressure, pachymetry and retinal nerve fiber layer (RNFL) and statistical differences between groups are presented in Table 1. The groups were similar in age and gender (p > 0.05). Snellen best-corrected visual acuity was 20/20 in all participants. Slit-lamp biomicroscopy and detailed fundus examinations were normal. No participants reported visual symptoms. FAZ areas were 0.390±0.81 mm 2 (superfacial) and 0.466±0.14 mm 2 (deep) in Group 1, and 0.337±0.12 mm 2 (superfacial) and 0.395±0.96 mm 2 (deep) in Group 2. Although the FAZ area was higher in Group 1, the difference was statistically significant only in the deep plexus(p=0.062 and p=0.022, respectively). In the superficial plexus (SCP), a significant difference between Groups 1 and 2 was observed only in the nasal quadrant (p=0.046). In the deep capillary plexus (DCP),vascular density was significantly reduced in Group 1 across all quardrants (nasal, temporal, superior, and inferior), with p-values of 0.008, 0.037, 0.011, and 0.001, respectively. Detailed data comparing FAZ, SCP, and DCP parameters between the two groups are shown in Table 2. Table1: Descriptive Statistics Group1(CRSwNP) Group2(Control) p value Age 34.17 ± 9.9(18-54) 32.40 ± 10.28 0.388 c Gender 52% Female /48% Male 50% Female /50% Male 0.785 b Intraocular pressure (mmHg) 15±2.8(10-22) 13.9±2.6(10-19) 0.481 a Pacymetry (µm) 544.72±21.63(500-610) 548.83±34.4(500-630) 0.318 a RNFL Average (µm) 110.31±10.48 93.22±11.50 0.007 a Macular Thickness Average (µm) 277.56 ± 15.82 282.94 ± 11.73 0.037 a Table 1: Demographic comparison of means. Continuous variables are presented as the mean ± standard deviation or median (min–max). Categorical variables are presented as number (%) a- Independent-samples t test, b-Chi Square test, c-Mann Whitney U ) Table 2 lists the averages of the entire image, superior, temporal, inferior and nasal VD of CRSwNp. (p < 0.05). Variables are presented as the mean ± standard deviation or median (min–max). a - Independent-samples t test, b - Chi Square test, c - Mann Whitney U Parameter Group1(CRSwN) (n=29) Avg±SD(Min-Max) Group2(Control)(n=30) Avg±SD(Min-Max) P value Superficial Capillary Plexus Values FAZ area(mm 2 ) 0,390±0,81(0,267-0.606) 0.337±0,12(0,125-0,652) 0,062 a VD Superior quadrant 49.41 ± 3.2(41.32-57.92) 49.18 ± 2.4(41.35-52.14) 0.716 c VD İnferior quadrant 48.29 ± 3.1(35.3-52.84) 48.32 ± 2.2(43.28-53.79) 0.170 c VD Nasal quadrant 47.53 ± 2.5(40.97-51.41) 48.75 ± 2.1(44.84-53.65) *0.046 a VD Temporal quadrant 48.81 ± 2.6(40.42-55.23) 48.13 ± 1.8(44.71-51.56) 0.118 c Central VDI 23.16 ± 3.9(15.71-29.35) 21.20 ± 4.3(12.24-29.13) 0.076 Deep Capillary Plexus Values FAZ area(mm 2 ) 0,466±0,14(0,161-0,860) 0,395±0,96(0,206-0,606) 0.022 c VD Superior quadrant 49.91 ± 3.6(40.07-60.43) 51.62 ± 2.7(42.44-56.14) 0.011 c VD İnferior quadrant 48.91 ± 3.7(34.77-55.30) 51.31 ± 2.3(45.54-54.29) *0.001 c VD Nasal quadrant 48.89 ± 2.4(44.46-54.22) 50.57 ± 2.3(45.73-56.60) *0.008 a VD Temporal quadrant 48.59 ± 3.6(36.87-58.64) 49.97 ± 2.0(45.99-53.58) *0.037 c Central VDI 20.89 ± 4.6(12.6-28.65) 19.45 ± 3.9(11.51-28.03) 0.200 a DISCUSSION Many systemic diseases affecting vascular tissue can be evaluated through the retinal vasculature, offering a unique opportunity for in vivo microcirculation imaging. Retinal and choroidal vasculature have been studied in various conditions, including hypertension, chronic obstructive pulmonary disease (COPD), carotid artery stenosis, and obstructive sleep apnea syndrome (OSAS), all of which impact tissue oxygenation[8-10,12]. CRSwNP is part of this group, as it alters nasal airflow and causes airway obstruction. The severity of nasal polyps is graded on a scale of 0 to 4. Polyps graded 3 or 4 are often associated with alternating periods of hypoxemia and hypercapnia[13]. Previous studies have reported peripheral oxygen desaturation [3] and elevated serum inflammatory markers [4] in patients with CRSwNP. Most earlier studies evaluating retinal changes in previously mentioned diseases have used OCT. Some studies investigating upper respiratory tract obstruction, such as OSAS, nasal polyps, septal deviation, adenoid hypertrophy, and choroidal thickness, with evidence of both thinning [14] and no significant change [15,16,17]. When evaluating these results, it should be noted that retinal and choroidal circulations differ fundamentally. The choroidal circulation has a larger circulation and is controlled by sympathetic innervation without autoregulation, whereas the retinal circulation exhibits autoregulation without autonomic innervation and is mainly influenced by local factors released by endothelial cells and surrounding tissue. It has been reported that retinal and choroidal endothelial cells have different responses to hypoxia and that there may be numerous biochemical reactions [18]. It should also be remembered that many vascular changes may begin in the retina before the onset of visual symptoms[18]. Given these differences, we decided to conduct a study considering that retinal circulation should be examined separately and that OCT findings with varying results could be supported by OCTA. To our knowledge, this is the first study evaluating OCTA parameters in patients with CRSwNP. We investigated whether there are measurable changes in the retina in CRSwNP. The FAZ area, which reflects parafoveal vascular dropout and foveal ischemia, was one of the parameters examined. We found that the FAZ area decreased in both the superficial and deep plexuses, with the decrease being statistically significant in the deep plexus. Although OCTA provides more effective measurement, especially in the superficial FAZ, it can also reveal the deep vascular layers more clearly than fluorescein angiography. In this study, the decrease in the superficial plexus was not statistically significant but was close to the significance threshold. Enlargement of the FAZ indicates macular ischemia and is consistent with decreased vascular density, particularly in the deep FAZ in CRSwNP group. It appears to be a manifestation of a hypoxic environment and vascular remodeling. Even under physiological conditions, the termination of vessels farther from the fovea in the deep layer may cause an increased FAZ area and a greater susceptibility to ischemic changes at the depth. This finding is consistent with other studies showing FAZ changes in ischemic diseases[19]. It is possible for a significant change in the FAZ area to occur even in the absence of visual symptoms. The present findings suggest that CRSwNP may cause problems related to ischemia in the macula and warrant close monitoring of visual function in the severe and chronic phases of the disease. Previous studies have reported that oxygen supply may affect the oxygen balance in the endothelium, which could alter the diameter, density, and area of the retinal capillary vessels [19,11]. The vessel diameter index (VDI) is defined as the ratio of the vessel area to vessel length. VDI provides vessel size information and is sensitive to vascular dilation[20,21]. Chu and colleagues found that VDI increased in diabetes and decreased after treatment. In this study, VDI was slightly higher in CRSwNP group than in the control group; howewer, we did not find a significant change in VDI. This finding may be attributed to the fact that CRSwNP does not directly damage vascular wall cells as diabetes does. Vessel density (VD), which reflects the ratio of the image area occupied by blood vessels, may reveal vessel abnormalities, including dropout zones in retina. The present study detected a significant decrease in vascular density in all quadrants of the DCP and in the nasal quadrant of the SCP compared to the control group . The decrease in VD in the deep plexus was consistent with the findings of Hommer et al.[22]. In their study, changes in superficial and deep capillary plexuses due to hyperoxia and hypoxia were investigated. The study indicated that hyperoxia mainly leads to constriction in the deep capillary plexus of the retina, whereas hypoxia leads to vasodilation mainly in the superficial layers. Similar long-term changes can be expected in nasal polyposis. CRSwNP is thought to cause hypoxia, changes in perfusion pressure, vasospasm, increased blood viscosity, and small vessel resistance, and may alter ocular tissues through these mechanisms. The severity of nasal polyposis significantly increases oxidative stress [23]. CRSwNP also induces dysregulation of nocturnal blood pressure [24]. The deep retinal plexsus is more vulnerable than the superficial layers due to the high metabolic demands of the retina. Our data suggest that differences in deep capillary microvasculature measured by OCTA may reflect the cumulative result of the mechanisms mentioned above. In CRSwNP, intermittent but prolonged reductions in microcirculatory oxygen levels appear to cause permanent structural changes. In fact, even in mild and temporary hypoxic situations, such as those experienced during air travel or when using protective face masks, can affect retinal tissue [25,26].Vascular reactivity enables adaptation to transient ischemia. However, in long-term conditions such as chronic disease, these vascular changes can become permanent structural changes. The severity and duration of disease are likelt key factors in the permanence of these changes. In previous studies on CRSwNP, retinal changes were found to be more subtle in patients at earlier stages [27]. In the current study, only patients with grade 3 or higher moderate-to-severe disease who had been diagnosed for more than two years were included. This indicates a stage at which the disease is both more prolonged and severe. Animal studies have shown that both hypoxia and hyperoxia are toxic to the retina, and that alternating between the two may increase toxicity [28]. Chronic hypoxic conditions have effects on macular thickness and the thickness of the retinal nerve fiber layer (RNFL) around the optic nerve head. In general, gradual decreases in capillary density result in reduced macular thickness, unlike acute ischemia, which causes macular edema. The study by Lin et al. found that macular thickness decreased under hypoxia and improved with oxygen therapy [29]. Similarly, in our study, macular thickness was significantly lower in the CRSwNP group. The effect of systemic hypoxia on RNFL remains controversial. Some studies in COPD patients reported thinning of RNLF [30], while others found no significant changes [31]. The literature on chronic rhinosinusitis cases, with or without nasal polyps, is limited. Karakahya et al. evaluated retinal changes using OCT [27]. RNFL was found to be significantly lower in the upper and lower quadrants in patients with nasal polyps compared to healthy controls. GC-IPL analysis showed that mean values were lower in patients with nasal polyps, although there was no significant difference in central macular thickness [27]. In the present study, RNFL values differed between groups, with RNLF reduced in the CRSwNP group. The variability in findings may be influenced by the severity, duration, and underlying etiology of the systemic hypoxia. Some systemic factors, such as age, contribute to changes in the eye’s vasculature. In addition, several characteristics or conditions in healthy subjects might be sources of bias and should be accounted for. In the current study, many systemic conditions that could have introduced bias were excluded and the control group was selected to have similar characteristics as much as possible. Reproducibility of OCTA values is a common limitation in such studies. There are varying data on reproducibility and reliability depending on the device, segmentation method, and imaging depth. In this study, we referenced literature on repeatability and reliability specific to the current TOPCON device. It is important to acknowledge that the areas of signal void on OCTA do not always indicate the absence of vascular flow, but may reflect reduced blood flow below the detection threshold of OCTA. We do not yet know the exact timing of when vascular changes occur following CRSwNP diagnosis and treatment. The time points used in this study were based on the clinical experience. Therefore, the current study excluded possible changes after treatment. The data obtained from this study support planning future studies with larger patient groups and the evaluation of changes following treatment. We believe that new comprehensive studies including subgroups representing comorbidities and inflammatory changes are necessary to obtain more meaningful information about the role of OCTA in the diagnosis and treatment of CRSwNP. Abbreviations CRSwNP -Chronic rhinosinusitis with nasal polyposis; OCTA - Optical coherence tomography angiography; VD – Vascular density; FAZ – Foveal avascular zone; RNFL – Retinal nerve fiber layer; VDI – Vessel diameter index References Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl S29):1-464. doi:10.4193/Rhin20.600. Özdemir R, Yorulmaz A, Kutlu R, et al. Loss of nocturnal decline of blood pressure in patients with nasal polyposis. Blood Press . 1999; 8(3):165–171. Bhattacharyya N. Does chronic rhinosinusitis relate to systemic hypoxemia? Laryngoscope Investig Otolaryngol. 2020;5(5):809-812. doi:10.1002/lio2.467 Kim DK, Lee BC, Park KJ, Son GM. Effect of Obstructive Sleep Apnea on Immunity in Cases of Chronic Rhinosinusitis With Nasal Polyps. Clin Exp Otorhinolaryngol . 2021;14(4):390-398. doi:10.21053/ceo.2020.02250 Dell'Omo R, Semeraro F, Bamonte G, Cifariello F, Romano MR, Costagliola C. 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Oxidative stress and nasal polyposis: does it affect the severity of the disease? Am J Rhinol Allergy . 2014 Jan-Feb;28(1):e1-4. doi: 10.2500/ajra.2014.28.3963. PMID: 24717866. Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps . J Allergy Clin Immunal Pract. 2016; 4 (4): 565-72. doi:10.1016/j.jaip.2016.04.012. Sousa DC, et al. Hypoxia challenge test and retinal circulation changes–a study using ocular coherence tomography angiography . Acta ophthalmologica 2018;96.3: e315-e319. Liang X, et al. OCTA quantitative assessment of exercise-induced variations and recovery in retinal microvasculature of healthy subjects with or without masks . Microvasc Res. 2024; 155: 104719. Karakahya RH, Korkmaz M, Korkmaz H. Decreased retinal nerve fiber and Choroidal thickness in chronic Rhinosinusitis. Eur Arch Otorhinolaryngology. 2021; 278: 2863-2868. Wellard J, Lee D, Valter K, Stone J . Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia. Vis Neurosc. 2005;22(4):501-507.doi:10.1017/S0952523805224112. 29. Lin PW, Lin HC, Friedman M, et al. Effects of CPAP for patients with OSA on visual sensitivity and retinal thickness. Sleep Med . 2020;67:156-163. doi:10.1016/j.sleep.2019.10.019. Wagh V, Tidake PK, Aurangabadkar G. The Role of Optical Coherence Tomography to Measure Retinal Nerve Fiber Layer Thickness in Patients with Chronic Obstructive Pulmonary Disease . Cureus. 2022;14:e25517. doi: 10.7759/cureus.25517. Kocamış Ö, Zorlu D. Choroid and retinal nerve fiber layer thickness in patients with chronic obstructive pulmonary disease exacerbation. J. Ophthalmol. 2018;2018:1201976. doi: 10.1155/2018/1201976. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviews received at journal 07 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers invited by journal 02 Nov, 2025 Editor assigned by journal 04 Jul, 2025 Submission checks completed at journal 04 Jul, 2025 First submitted to journal 02 Jul, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7032382","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":541827085,"identity":"4b608d83-02cb-4a10-a724-af68787a663f","order_by":0,"name":"Tülin Öğreden","email":"","orcid":"","institution":"University of Health Sciences, Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tülin","middleName":"","lastName":"Öğreden","suffix":""},{"id":541827087,"identity":"0943a8ca-0615-44ad-ada1-781bd8c17af7","order_by":1,"name":"Gülistan Oyur","email":"","orcid":"","institution":"University of Health Sciences, Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gülistan","middleName":"","lastName":"Oyur","suffix":""},{"id":541827088,"identity":"1264e230-9cc9-49c4-af98-891411985df7","order_by":2,"name":"Özgü Canbolat","email":"","orcid":"","institution":"University of Health Sciences, Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Özgü","middleName":"","lastName":"Canbolat","suffix":""},{"id":541827089,"identity":"0c3c51f8-0e73-4ae4-b21a-2330fa3edf5f","order_by":3,"name":"Şahin Öğreden","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDCCAwwMzAwGELYEA4MNkGJsPECKljSQlgYitDDAtRyGCeIGfLePP/xcUHBHTj768MEbH3ect1vbfhhoS41NNC4tkudyjKVnGDwzNjyXlmw588zt5G1nEoFajqXlNuDQYnCGh0Gax+Bw4sYeHjNp3rbbyWYHgFoYGw7j0cL++DdEC/836b9t55LNzj8kpIXBDGzLfB4eNmnGtgN2ZjcI2CJ5hsfMGqjF2ICHzdiyty05wewG0JYEPH7hAzrsNs+fw3LyPcwPb/xss7M3O5/+8MGHGhucWhAuPAChE8EqEwgpBwF5qKH2xCgeBaNgFIyCkQUApRBj9Sz0qpcAAAAASUVORK5CYII=","orcid":"","institution":"University of Health Sciences, Basaksehir Cam and Sakura City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Şahin","middleName":"","lastName":"Öğreden","suffix":""}],"badges":[],"createdAt":"2025-07-02 20:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7032382/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7032382/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95876990,"identity":"89ecfbb5-de02-4676-b718-23a8a0d9447e","added_by":"auto","created_at":"2025-11-14 01:40:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":244659,"visible":true,"origin":"","legend":"\u003cp\u003eOCTA en face İmage showing four equal quadrants (temporal, nasal, inferior, and superior) and central area.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7032382/v1/286370f9388d65626d472360.jpg"},{"id":96452757,"identity":"1681211f-f080-4fce-bf29-ad2c7a061cbe","added_by":"auto","created_at":"2025-11-21 09:41:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":698725,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7032382/v1/5fbbd5bb-0870-4d48-8eb8-4213ca0e6f5b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"OCT Angiography Parameters in Nasal Polyposis Associated with Chronic Rhinosinusitis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eChronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and the linings of the nasal passages that persists for 12 weeks or longer. \u0026nbsp;It is a relatively common condition affecting all age groups. CRS is classified into three types: CRS with nasal polyposis (CRSwNP), which accounts for 20 to 33% of cases; allergic fungal rhinosinusitis (AFRS); and CRS without nasal polyposis (CRSsNP)[1].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CRSwNP is among the diseases that impair nasal airway flow and tissue oxygenation by causing obstruction. Symptoms of CRSwNP include anosmia, facial pressure, nasal drainage, and nasal obstruction. Chronic obstruction may result in hypoxia and persistently low oxygen saturation. \u0026nbsp;This contributes to increased vasoactive responses, systemic hypertension, and loss of the physiological nocturnal decrease in blood pressure[2].\u0026nbsp; Prior studies have demonstrated changes in oxygen saturation[3]\u0026nbsp;\u0026nbsp;and elevated serum inflammatory markers in patients with CRSwNP\u0026nbsp;[4].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The retina is one of the most metabolically active tissues and has the highest oxygen demand per unit area in the body. The vascular system that nourishes the retina is directly influenced by blood oxygen levels. While the retina can autoregulate in response to acute changes in saturation, repeated and prolonged hypoxic attacks may result in permanent structural changes in the retinal vasculature[5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRetinal tissue alterations can be assessed quantitatively and qualitatively using advanced imaging technologies. Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging modality that provides detailed visualization of blood flow and the retinal-choroidal capillary network\u0026nbsp;[6].\u0026nbsp;Its primary applications are in retinal, choroidal, anterior segment, and optic nerve disorders\u0026nbsp;[7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOCTA is also increasingly used to assess the ocular effects of systemic disorders, even in the absence of primary ocular pathology\u0026nbsp;[8].\u0026nbsp;Measuring retinal microcirculation using OCTA may offer valuable insights into the preclinical hemodynamic of CRSwNP on the eye.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Previous studies have shown that retinal nerve fiber layer (RNFL) thickness and retinal-choroidal vascular structures may be altered in systematic conditions such as obstructive sleep apnea syndrome, coronary artery disease, and carotid artery stenosis, as demonstrated by OCTA\u0026nbsp;[8,9,10,11].\u0026nbsp;However, to our knowledge, no previous studies have investigated the impact of CRSwNP on the retinal capillary network by OCTA imaging.\u0026nbsp;\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eParticipants and Data Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective, cross-sectional study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Başakşehir \u0026Ccedil;am and Sakura City City Hospital ( Approval No. 2022.04.113). Informed consent was obtained from all participants included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to the criteria outlined in the European Position Paper on Rhinosinusitis and Nasal Polyps 2020, the diagnosis of chronic rhinosinusitis (CRS) was based \u0026nbsp; on the presence of at least two of the four cardinal symptoms: anterior and/or posterior mucopurulent nasal drainage, nasal obstruction/nasal blockage/congestion, facial pain, pressure, and/or fullness, and reduction or loss of sense of smell. Nasal polyps were confirmed by rhinoscopy (with decongestion) and nasal endoscopy, through direct visualization of the nasal cavity. The severity of nasal polyps was graded on a scale from 0 to 4.\u003c/p\u003e\n\u003cp\u003ePatients with CRSwNP and healthy volunteers (control group) were followed in the Otolaryngology and Ophthalmology Departments of Başakşehir \u0026Ccedil;am and Sakura City Hospital between April 2022 and July 2023. A total of\u0026nbsp;29 eyes of 29 CRSwNP participants and 30 eyes of 30 individuals in the healthy control group were included.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll participants underwent best-corrected visual acuity (BCVA) assessment using Snellen chart, slit-lamp biomicroscopy, tonometry, and OCTA imaging. One eye (left) of each participant was included in the analysis. OCTA imaging was performed using 6 mm \u0026times; 6 mm macular scan. The following parameters were analyzed : retinal vascular density (VD) in four quadrants (both superficial and deep capillary plexuses), vessel diameter index (VDI), and foveal avascular zone (FAZ) area.\u003c/p\u003e\n\u003cp\u003eInclusion criteria were as follows: patients with nasal polyps graded \u0026ge;3 and significant airway obstruction were included in the study group.\u0026nbsp;Only patients with a confirmed CRSwNP diagnosis of at least 2 years were enrolled. Pulse oximetry was performed prior to the ophthalmologic examination, \u0026nbsp;and only cases with oxygen saturation levels above 90% were considered eligible. All participants in the study group had a best-corrected visual acuity (BCVA) of 20/20 and no additional respiratory or ocular pathology.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were as follows: presence of refractive errors affecting visual acuity; corneal, lens or vitreous pathologies; retinal vascular diseases, dystrophies, \u0026nbsp;or any form of macular degeneration; ocular surgery within the past six months; ocular ischemic syndrome; pulmonary diseases affecting blood oxygen levels (e.g., chronic obstructive pulmonary disease); history of treated or untreated airway stenosis; \u0026nbsp;systemic vascular diseases \u0026nbsp;such as diabetes mellitus and hypertension; dyslipidemia; obstructive sleep apnea syndrome; and a body mass index greater than 25.\u003c/p\u003e\n\u003cp\u003eAge- and sex-matched controls were included in this study. \u0026nbsp;The control group consisted of volunteers visiting the eye clinic who had at least 20/20 BCVA, no systemic or ocular pathology, and oxygen saturation \u0026gt;90% as measured by pulse oximetry. The same exclusion criteria were applied to the control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOCTA Imaging Protocol:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll OCTA imaging was performed by an experienced technician who was blinded to the clinical status of the participants. Imaging was obtained using the Topcon DRI OCT Triton Swept Source-device (Topcon Corporation, Tokyo, Japan), which operates at an A-scan repetition rate of 100.000 kHz, with a 1050 nm wavelength and a tissue depth resolution of 2 \u0026micro;m. The device has a full width at half-maximum of 100 nm \u0026nbsp;and a lateral resolution on the retinal surface of 15 \u0026micro;m.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore imaging, each participant received pupil dilation with 0.5% tropicamide and 2.5% phenylephrine.\u0026nbsp;A 6 \u0026times; 6 mm scanning area centered on the fovea was used for image acquisition. Each scan was repeated three times during acquisition.\u003c/p\u003e\n\u003cp\u003eThe macular area was automatically divided into four equal quadrants (temporal, nasal, inferior, and superior) and a central circular zone (Figure 1). The inner retinal lamina was defined as the area between the internal limiting membrane and the outer plexiform layer (OPL), and the outer retina as the area between the Bruch\u0026rsquo;s membrane and the inner nuclear layer/OPL junction. \u0026nbsp;The superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed using the device\u0026rsquo;s \u0026nbsp;built-in default segmentation boundaries. Manual segmentation was performed in cases with evident segmentation artifacts.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe evaluated the following quantitative parameters: \u0026nbsp; foveal avascular zone (FAZ), vessel density (VD), and vessel diameter index (VDI). The FAZ area was automatically measured using the device\u0026rsquo;s embedded FAZ assessment tool. \u0026nbsp;Vascular density(VD) was defined as the percentage of the area occupied by large vessels and microvasculature. The vessel diameter index (VDI) was calculated as the ratio of the total vessel area to vessel length. In addition to these parameters, mean macular thickness and retinal nerve fiber layer (RNFL) thickness were measured using the optical coherence tomography \u0026nbsp;(OCT) mode of the device.\u003c/p\u003e\n\u003cp\u003eLow-quality scans were excluded and repeated until a satisfactory signal strength index was achieved. OCTA images containing motion artifacts or flashing artifacts that could affect analysis were also excluded.\u003c/p\u003e\n\u003cp\u003eFigure1: OCTA en face İmage showing four equal quadrants (temporal, nasal, inferior, and superior) and central area.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), Version 22.0 for Windows (SPSS Inc., Chicago, IL, USA). Descriptive statistics are presented as mean \u0026plusmn; standard deviation, along with minimum and maximum values for numerical variables. Pearson\u0026rsquo;s chi-square test and the one-sample chi-square test were used for categorical variables.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor comparisons between groups, the independent sample t-test was used for normally distributed data, while Mann-Whitney U test was applied for non-normally distributed data. A p-value of \u0026lt;0.05 was considered statistically significant.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eCases diagnosed with CRSwNP were defined as Group 1, and the control group as Group 2. Group 1 consisted of 29 patients, and Group 2 included 30 individuals. Data from one eye per participant were analyzed. The mean age of Group 1 (52.0% female) was 34.17 \u0026plusmn; 9.9 years, and the mean age of Group 2 (50% female) was 32.40 \u0026plusmn; 10.28 years. Descriptive data on age, gender, Intraocular pressure, pachymetry and retinal nerve fiber layer (RNFL) and statistical differences between groups are presented in Table 1. The groups were similar in age and gender (p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eSnellen best-corrected visual acuity was 20/20 in all participants. Slit-lamp biomicroscopy and detailed fundus examinations were normal. No participants reported visual symptoms.\u003c/p\u003e\n\u003cp\u003eFAZ areas were 0.390\u0026plusmn;0.81 mm\u003csup\u003e2\u003c/sup\u003e(superfacial) and 0.466\u0026plusmn;0.14 mm\u003csup\u003e2\u003c/sup\u003e (deep) in Group 1, and 0.337\u0026plusmn;0.12 mm\u003csup\u003e2\u003c/sup\u003e (superfacial) and 0.395\u0026plusmn;0.96 mm\u003csup\u003e2\u003c/sup\u003e (deep) in Group 2. Although the FAZ area was higher in Group 1, the difference was statistically significant only in the deep plexus(p=0.062 and p=0.022, respectively).\u003c/p\u003e\n\u003cp\u003eIn the superficial plexus (SCP), a significant difference between Groups 1 and 2 was observed only in the nasal quadrant (p=0.046). In the deep capillary plexus (DCP),vascular density was significantly reduced in Group 1 across all quardrants (nasal, temporal, superior, and inferior), with p-values of 0.008, 0.037, 0.011, and 0.001, respectively. Detailed data comparing FAZ, SCP, and DCP parameters between the two groups are shown in Table 2.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable1: \u0026nbsp;Descriptive Statistics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eGroup1(CRSwNP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003eGroup2(Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 34.17 \u0026plusmn; 9.9(18-54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;32.40 \u0026plusmn; 10.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.388\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003eGender \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e52%\u0026nbsp;Female /48%\u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e50%\u0026nbsp;Female /50%\u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.785\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003eIntraocular pressure\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e15\u0026plusmn;2.8(10-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 13.9\u0026plusmn;2.6(10-19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.481\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003ePacymetry (\u0026micro;m)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;544.72\u0026plusmn;21.63(500-610)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 548.83\u0026plusmn;34.4(500-630)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.318\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003eRNFL Average\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026micro;m)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;110.31\u0026plusmn;10.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 93.22\u0026plusmn;11.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.007\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003eMacular Thickness \u0026nbsp;Average \u0026nbsp;(\u0026micro;m)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;277.56 \u0026plusmn; 15.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 282.94 \u0026plusmn; 11.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.037\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTable 1: Demographic comparison of means.\u0026nbsp;Continuous variables are presented as the mean \u0026plusmn; standard deviation or median (min\u0026ndash;max). Categorical variables are presented as number (%) a- Independent-samples t test, b-Chi Square test, c-Mann Whitney U )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2 lists the averages of the entire image, superior, temporal, inferior and nasal VD of CRSwNp. (p \u0026lt; 0.05). Variables are presented as the mean \u0026plusmn; standard deviation or median (min\u0026ndash;max). a\u003cstrong\u003e-\u003c/strong\u003e Independent-samples t test, b\u003cstrong\u003e-\u003c/strong\u003eChi Square test, c\u003cstrong\u003e-\u003c/strong\u003eMann Whitney U\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 330px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 330px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eGroup1(CRSwN)\u0026nbsp;(n=29)\u003c/p\u003e\n \u003cp\u003eAvg\u0026plusmn;SD(Min-Max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Group2(Control)(n=30)\u003c/p\u003e\n \u003cp\u003eAvg\u0026plusmn;SD(Min-Max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSuperficial Capillary Plexus Values\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eFAZ area(mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e0,390\u0026plusmn;0,81(0,267-0.606)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e0.337\u0026plusmn;0,12(0,125-0,652)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0,062\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Superior quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e49.41 \u0026plusmn; 3.2(41.32-57.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e49.18 \u0026plusmn; 2.4(41.35-52.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.716\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD İnferior quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e48.29 \u0026plusmn; 3.1(35.3-52.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e48.32 \u0026plusmn; 2.2(43.28-53.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.170\u003csup\u003e\u0026nbsp;c\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Nasal quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e47.53 \u0026plusmn; 2.5(40.97-51.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e48.75 \u0026plusmn; 2.1(44.84-53.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e*0.046\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Temporal quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e48.81 \u0026plusmn; 2.6(40.42-55.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e48.13 \u0026plusmn; 1.8(44.71-51.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.118\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCentral VDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e23.16 \u0026plusmn; 3.9(15.71-29.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e21.20 \u0026plusmn; 4.3(12.24-29.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eDeep Capillary Plexus Values\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eFAZ area(mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e0,466\u0026plusmn;0,14(0,161-0,860)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e0,395\u0026plusmn;0,96(0,206-0,606)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.022\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Superior quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e49.91 \u0026plusmn; 3.6(40.07-60.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e51.62 \u0026plusmn; 2.7(42.44-56.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.011\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD İnferior quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e48.91 \u0026plusmn; 3.7(34.77-55.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e51.31 \u0026plusmn; 2.3(45.54-54.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e*0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Nasal quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e48.89 \u0026plusmn; 2.4(44.46-54.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e50.57 \u0026plusmn; 2.3(45.73-56.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e*0.008\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVD Temporal quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e48.59 \u0026plusmn; 3.6(36.87-58.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e49.97 \u0026plusmn; 2.0(45.99-53.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e*0.037\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCentral VDI\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e20.89 \u0026plusmn; 4.6(12.6-28.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e19.45 \u0026plusmn; 3.9(11.51-28.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.200\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMany systemic diseases affecting vascular tissue can be evaluated through the retinal vasculature, offering a unique opportunity for in vivo microcirculation imaging.\u0026nbsp;Retinal and choroidal vasculature have been studied in various conditions, including hypertension, chronic obstructive pulmonary disease (COPD), carotid artery stenosis, and obstructive sleep apnea syndrome (OSAS), all of which impact tissue oxygenation[8-10,12].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CRSwNP is part of this group, as it alters nasal airflow and causes airway obstruction. The severity of nasal polyps is graded on a scale of 0 to 4. Polyps graded 3 or 4 are often associated with alternating periods of hypoxemia and hypercapnia[13].\u0026nbsp;Previous studies have reported peripheral oxygen desaturation\u0026nbsp;[3]\u0026nbsp;and elevated serum inflammatory markers\u0026nbsp;[4]\u0026nbsp;in patients with CRSwNP.\u003c/p\u003e\n\u003cp\u003eMost earlier studies evaluating retinal changes in previously mentioned diseases have used OCT. Some studies investigating upper respiratory tract obstruction, such as OSAS, nasal polyps, septal deviation, adenoid hypertrophy, and choroidal thickness, with evidence of both thinning [14] and no significant change [15,16,17].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;When evaluating these results, it should be noted that retinal and choroidal circulations differ fundamentally. The choroidal circulation has a larger circulation and is controlled by sympathetic innervation without autoregulation, whereas the retinal circulation exhibits autoregulation without autonomic innervation and is mainly influenced by local factors released by endothelial cells and surrounding tissue. It has been reported that retinal and choroidal endothelial cells have different responses to hypoxia and that there may be numerous biochemical reactions\u0026nbsp;[18]. It should also be remembered that many vascular changes may begin in the retina before the onset of visual symptoms[18].\u003c/p\u003e\n\u003cp\u003eGiven these differences, we decided to conduct a study considering that retinal circulation should be examined separately and that OCT findings with varying results could be supported by OCTA. To our knowledge, this is the first study evaluating OCTA parameters in patients with CRSwNP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe investigated whether there are measurable changes in the retina in CRSwNP. The FAZ area, which reflects parafoveal vascular dropout and foveal ischemia, was one of the parameters examined. We found that the FAZ area decreased in both the superficial and deep plexuses, with the decrease being statistically significant in the deep plexus. Although OCTA provides more effective measurement, especially in the superficial FAZ, it can also reveal the deep vascular layers more clearly than fluorescein angiography. In this study, the decrease in the superficial plexus was not statistically significant but was close to the significance threshold. Enlargement of the FAZ indicates macular ischemia and is consistent with decreased vascular density, particularly in the deep FAZ in CRSwNP group. It appears to be a manifestation of a hypoxic environment and vascular remodeling.\u0026nbsp;Even under physiological conditions, \u0026nbsp;the termination of vessels farther from the fovea in the deep layer may cause an increased FAZ area and a greater susceptibility to ischemic changes at the depth.\u0026nbsp;This finding is consistent with other studies showing FAZ changes in ischemic diseases[19].\u0026nbsp;It is possible for a significant change in the FAZ area to occur even in the absence of visual symptoms.\u0026nbsp;The present findings suggest that CRSwNP may cause problems related to ischemia in the macula and warrant close monitoring of visual function in the severe and chronic phases of the disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Previous studies have reported that oxygen supply may affect the oxygen balance in the endothelium, which could alter the diameter, density, and area of the retinal capillary vessels\u0026nbsp;[19,11]. The vessel diameter index (VDI) is defined as the ratio of the vessel area to vessel length.\u0026nbsp;VDI provides vessel size information and is sensitive to vascular dilation[20,21]. Chu and colleagues found that VDI increased in diabetes and decreased after treatment.\u0026nbsp;In this study, VDI was slightly higher in CRSwNP group than in the control group; howewer, we did not find a significant change in VDI. This finding may be attributed to the fact that CRSwNP does not directly damage vascular wall cells as diabetes does.\u003c/p\u003e\n\u003cp\u003eVessel density (VD), which reflects the ratio of the image area occupied by blood vessels, \u0026nbsp;may reveal vessel abnormalities, including dropout zones in retina. The present study detected a significant decrease in vascular density in all quadrants of the DCP and in the nasal quadrant of the SCP compared to the control group\u003cstrong\u003e.\u003c/strong\u003e The decrease in VD in the deep plexus was consistent with the findings of Hommer et al.[22]. In their study, changes in superficial and deep capillary plexuses due to hyperoxia and hypoxia were investigated. The study indicated that hyperoxia mainly leads to constriction in the deep capillary plexus of the retina, whereas hypoxia leads to vasodilation mainly in the superficial layers. Similar long-term changes can be expected in nasal polyposis. CRSwNP is thought to cause hypoxia, changes in perfusion pressure, vasospasm, increased blood viscosity, and small vessel resistance, and may alter ocular tissues through these mechanisms.\u0026nbsp;The severity of nasal polyposis significantly increases oxidative stress\u0026nbsp;[23]. CRSwNP also induces dysregulation of nocturnal blood pressure\u0026nbsp;[24]. The deep retinal plexsus is more vulnerable than the superficial layers due to \u0026nbsp;the high metabolic demands of the retina.\u0026nbsp;Our data suggest that differences in deep capillary microvasculature measured by OCTA may reflect the cumulative result of the mechanisms mentioned above. In CRSwNP, intermittent but prolonged reductions in microcirculatory oxygen levels appear to cause permanent structural changes.\u003c/p\u003e\n\u003cp\u003eIn fact, even in mild and temporary hypoxic situations, such as those experienced during air travel or when using protective face masks, can affect retinal tissue\u0026nbsp;[25,26].Vascular reactivity enables adaptation to transient ischemia. However, in long-term conditions such as chronic disease, these vascular changes can become permanent structural changes. The severity and duration of disease are likelt key factors in the permanence of these changes. In previous studies on CRSwNP, retinal changes were found to be more subtle in patients at earlier stages\u0026nbsp;[27].\u0026nbsp;In the current study, only patients with grade 3 or higher moderate-to-severe disease who had been diagnosed for more than two years were included. This indicates a stage at which the disease is both more prolonged and severe.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnimal studies have shown that both hypoxia and hyperoxia are toxic to the retina, and that alternating between the two may increase toxicity\u0026nbsp;[28]. Chronic hypoxic conditions have effects on macular thickness and the thickness of the retinal nerve fiber layer (RNFL) around the optic nerve head.\u0026nbsp;In general,\u0026nbsp;gradual\u0026nbsp;decreases in capillary density result in reduced macular thickness, unlike acute ischemia, which causes macular edema.\u0026nbsp;The study by Lin et al. found that macular thickness decreased under hypoxia and improved with oxygen therapy\u0026nbsp;[29].\u0026nbsp;Similarly, in our study, macular thickness was significantly lower in the CRSwNP group.\u003c/p\u003e\n\u003cp\u003eThe effect of systemic hypoxia on RNFL remains controversial. Some studies in COPD patients reported thinning of RNLF\u0026nbsp;[30], while others found no significant changes\u0026nbsp;[31]. The literature on chronic rhinosinusitis cases, with or \u0026nbsp;without nasal polyps, is limited. Karakahya et al. evaluated retinal changes using OCT\u0026nbsp;[27]. RNFL was found to be significantly lower in the upper and lower quadrants in patients with nasal polyps compared to healthy controls. GC-IPL analysis showed that mean values were lower in patients with nasal polyps, although there was no significant difference in central macular thickness\u0026nbsp;[27]. In the present study, RNFL values differed between groups, with RNLF reduced in the CRSwNP group. The variability in findings may be influenced by the severity, duration, \u0026nbsp;and underlying etiology of the systemic hypoxia.\u003c/p\u003e\n\u003cp\u003eSome systemic factors, such as age, contribute to changes in the eye’s vasculature. In addition, several characteristics or conditions in healthy subjects might be sources of bias and should be accounted for. In the current study, many systemic conditions that could have introduced bias were excluded and the control group was selected to have similar characteristics as much as possible.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Reproducibility of OCTA values is a common limitation in such studies.\u0026nbsp;There are varying data on reproducibility and reliability depending on the \u0026nbsp;device, segmentation method, and imaging depth.\u0026nbsp;In this study, we referenced literature on repeatability and reliability specific to the current TOPCON device. It is important to acknowledge that\u0026nbsp;the areas of signal void on OCTA do not always indicate the absence of vascular flow, but may reflect reduced blood flow below the detection threshold of OCTA.\u003c/p\u003e\n\u003cp\u003eWe do not yet know the exact timing of when vascular changes occur following CRSwNP diagnosis and treatment. The time points used in this study were based on the clinical experience. Therefore, the current study excluded possible changes after treatment. The data obtained from this study support planning future studies with larger patient groups and the evaluation of changes following treatment.\u003c/p\u003e\n\u003cp\u003eWe believe that new comprehensive studies including subgroups representing comorbidities and inflammatory changes are necessary to obtain more meaningful information about the role of OCTA in the diagnosis and treatment of CRSwNP.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRSwNP -Chronic rhinosinusitis with nasal polyposis; \u0026nbsp;OCTA - Optical coherence tomography angiography; VD \u0026ndash; Vascular density; FAZ \u0026ndash; Foveal avascular zone; RNFL \u0026ndash; Retinal nerve fiber layer; VDI \u0026ndash; Vessel diameter index\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFokkens WJ, Lund VJ, Hopkins C, et al. \u003cem\u003eEuropean Position Paper on Rhinosinusitis and Nasal Polyps\u003c/em\u003e 2020. Rhinology. 2020;58(Suppl S29):1-464. doi:10.4193/Rhin20.600.\u003c/li\u003e\n\u003cli\u003e\u0026Ouml;zdemir R, Yorulmaz A, Kutlu R, et\u0026nbsp;al. \u003cem\u003eLoss of nocturnal decline of blood pressure in patients with nasal polyposis. \u003c/em\u003eBlood Press\u003cem\u003e. \u003c/em\u003e1999; 8(3):165\u0026ndash;171.\u003c/li\u003e\n\u003cli\u003eBhattacharyya N. \u003cem\u003eDoes chronic rhinosinusitis relate to systemic hypoxemia?\u0026nbsp;Laryngoscope Investig Otolaryngol.\u003c/em\u003e 2020;5(5):809-812. doi:10.1002/lio2.467\u003c/li\u003e\n\u003cli\u003eKim DK, Lee BC, Park KJ, Son GM. Effect of Obstructive Sleep Apnea on Immunity in Cases of Chronic Rhinosinusitis With Nasal Polyps.\u0026nbsp;\u003cem\u003eClin Exp Otorhinolaryngol\u003c/em\u003e. 2021;14(4):390-398. doi:10.21053/ceo.2020.02250\u003c/li\u003e\n\u003cli\u003eDell'Omo R, Semeraro F, Bamonte G, Cifariello F, Romano MR, Costagliola C. \u003cem\u003eVitreous mediators in retinal hypoxic diseases.\u0026nbsp;Mediators Inflamm. \u003c/em\u003e2013;2013:935301. doi:10.1155/2013/935301.\u003c/li\u003e\n\u003cli\u003eBatıoğlu F, Yanık \u0026Ouml;, Demirel S, \u0026Ouml;zmert E\u003cem\u003e. Clinical Use of Optical Coherence Tomography Angiography in Retinal Diseases.\u0026nbsp;Diagnostics \u003c/em\u003e(Basel). 2023;13(10):1820. doi:10.3390/diagnostics13101820\u003c/li\u003e\n\u003cli\u003e7. Tan ACS, Tan GS, Denniston AK, et al. \u003cem\u003eAn overview of the clinical applications of optical coherence tomography angiography.\u0026nbsp;Eye \u003c/em\u003e(Lond). 2018;32(2):262-286. doi:10.1038/eye.2017.181\u003c/li\u003e\n\u003cli\u003eMonteiro-Henriques I, Rocha-Sousa A, Barbosa-Breda J. \u003cem\u003eOptical coherence tomography angiography changes in cardiovascular systemic diseases and risk factors: A Review\u003c/em\u003e.\u0026nbsp;\u003cem\u003eActa Ophthalmol\u003c/em\u003e. 2022;100(1):e1-e15. doi:10.1111/aos.14851\u003c/li\u003e\n\u003cli\u003eCai, Y, Sun, GS, Zhao L,\u0026nbsp;et al.\u003cem\u003eQuantitative evaluation of retinal microvascular circulation in patients with obstructive sleep apnea\u0026ndash;hypopnea using optical coherence tomography angiography\u003c/em\u003e.\u0026nbsp;\u003cem\u003eInt Ophthalmol\u003c/em\u003e2020; 40, 3309\u0026ndash;3321\u003c/li\u003e\n\u003cli\u003eSongur MS, İntepe YS, Bayhan SA, Bayhan HA, \u0026Ccedil;ift\u0026ccedil;i B, \u0026Ccedil;ıtırık M. \u003cem\u003eThe alterations of retinal vasculature detected on optical coherence tomography angiography associated with chronic obstructive pulmonary disease. \u003c/em\u003eClin Respir J. 2022;16(4):284-292. doi:10.1111/crj.13478\u003c/li\u003e\n\u003cli\u003eAlkan AA, Duzgun E, Karapapak M, et al. \u003cem\u003eRetinal Vascular Changes in Patients with Chronic Obstructive Pulmonary Disease: An Optical Coherence Tomography Angiography Study\u003c/em\u003e.\u0026nbsp;\u003cem\u003eSisli Etfal Hastan Tip Bul\u003c/em\u003e. 2021;55(2):210-216. doi:10.14744/SEMB.2020.28000\u003c/li\u003e\n\u003cli\u003eKarapapak M, Ermis S, Aks\u0026ouml;z Bolat P, et al. \u003cem\u003eChanges in retinal vascular density measured by optical coherence tomography angiography in patients with carotid artery stenosis after carotid artery stenting and angioplasty\u003c/em\u003e.\u0026nbsp;\u003cem\u003eInt Ophthalmol\u003c/em\u003e. 2024;44(1):128. doi:10.1007/s10792-024-03069-x\u003c/li\u003e\n\u003cli\u003eMalm, L \u003cem\u003eAssessment and staging of nasal polyposis: introduction\u003c/em\u003e.\u0026nbsp;\u003cem\u003eActa oto-laryngologica\u003c/em\u003e 1997; 117.4: 465-467.\u003c/li\u003e\n\u003cli\u003eTapan \u0026Ouml;O, Tapan U, Kılı\u0026ccedil; \u0026Uuml;S. \u003cem\u003eEffects of hypoxia on the eye in patients with obstructive sleep apnea syndrome]. Journal of Turkish Sleep Medicine\u003c/em\u003e. 2016;2:43-7.\u003c/li\u003e\n\u003cli\u003eElibol, ES, Doğan, R, Elbay, A, Cırık, AA, Aykut, V, Yenig\u0026uuml;n A.\u003cem\u003e Nazal Polipi Olan Hastaların Koroid Kalınlığının Değerlendirilmesi\u003c/em\u003e.\u0026nbsp;\u003cem\u003eJournal of Ear Nose Throat and Head Neck Surgery\u003c/em\u003e,\u0026nbsp;2020;\u003cem\u003e28\u003c/em\u003e(3).\u003c/li\u003e\n\u003cli\u003e\u0026Uuml;st\u0026uuml;n Bezgin S, \u0026Ccedil;akabay T, Bayramoğlu SE, Sayın N, Ko\u0026ccedil;yiğit M. \u003cem\u003eEvaluation of choroidal thickness measurements in patients with marked nasal septal deviation\u003c/em\u003e. Braz J Otorhinolaryngol. 2020 Mar-Apr;86(2):242-246. doi: 10.1016/j.bjorl.2018.11.009. Epub 2018 Dec 31. PMID: 30683564; PMCID: PMC9422583.\u003c/li\u003e\n\u003cli\u003eCakabay T, \u0026Uuml;st\u0026uuml;n Bezgin S, Bayramoglu SE, Sayin N, Kocyigit M. \u003cem\u003eEvaluation of choroidal thickness in children with adenoid hypertrophy\u003c/em\u003e. Eur Arch Otorhinolaryngol. 2018;275(2):439-442. doi: 10.1007/s00405-017-4846-7. Epub 2018 Jan 8. PMID: 29313145.\u003c/li\u003e\n\u003cli\u003eAlizadeh E, Mammadzada P, Andr\u0026eacute;, H. \u003cem\u003eThe Different Facades of Retinal and Choroidal Endothelial Cells in Response to Hypoxia.\u003c/em\u003e\u003cem\u003eInt. J. Mol. Sci.\u003c/em\u003e2018;\u0026nbsp;\u003cem\u003e19\u003c/em\u003e, 3846.\u003c/li\u003e\n\u003cli\u003eRakusiewicz K, et al. \u003cem\u003eUsefulness of retinal optical coherence tomography angiography evolution in cases of systemic diseases.\u003c/em\u003e \u003cem\u003eKlinika Oczna/Acta Ophthalmologica Polonica\u003c/em\u003e. 2021;123.4 (2021): 166-172.\u003c/li\u003e\n\u003cli\u003eChu Z, et al. \u003cem\u003eQuantitative assessment of the retinal microvasculature using optical coherence tomography angiography\u003c/em\u003e. J Biomed Opt. 2016; 21,6: 66008. doi:10.1117/1.JBO.21.6.066008.\u003c/li\u003e\n\u003cli\u003eKim AY, Chu ZD, Shahidzadeh A, Wang RKK, Puliafito CA, Kashani AH. \u003cem\u003eQuantifying microvascular density and morphology in diabetic retinopathy using spectral-domain optical coherence tomography angiography.\u003c/em\u003e Invest Ophthalmol Vis Sci. 2016;57:OCT362\u0026ndash;OCT370.\u003c/li\u003e\n\u003cli\u003eHommer N, et al. \u003cem\u003eEffect of hyperoxia and hypoxia on retinal vascular parameters assessed with optical coherence tomography angiography\u003c/em\u003e. \u003cem\u003eActa Ophthalmologica\u003c/em\u003e2022; 100.6: e1272-e1279.\u003c/li\u003e\n\u003cli\u003eTopal O, Kulaksızoglu S, Erbek SS. \u003cem\u003eOxidative stress and nasal polyposis: does it affect the severity of the disease? Am J Rhinol Allergy\u003c/em\u003e. 2014 Jan-Feb;28(1):e1-4. doi: 10.2500/ajra.2014.28.3963. PMID: 24717866.\u003c/li\u003e\n\u003cli\u003eStevens WW, et al. \u003cem\u003eChronic Rhinosinusitis with Nasal Polyps\u003c/em\u003e.\u0026nbsp;\u003cem\u003eJ Allergy Clin Immunal Pract. 2016;\u003c/em\u003e 4 (4): 565-72. doi:10.1016/j.jaip.2016.04.012.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"25\"\u003e\n\u003cli\u003eSousa DC, et al. \u003cem\u003eHypoxia challenge test and retinal circulation changes\u0026ndash;a study using ocular coherence tomography angiography\u003c/em\u003e.\u0026nbsp;\u003cem\u003eActa ophthalmologica\u003c/em\u003e 2018;96.3: e315-e319.\u003c/li\u003e\n\u003cli\u003eLiang X, et al. \u003cem\u003eOCTA quantitative assessment of exercise-induced variations and recovery in retinal microvasculature of healthy subjects with or without masks\u003c/em\u003e.\u0026nbsp;\u003cem\u003eMicrovasc Res. 2024;\u003c/em\u003e155: 104719.\u003c/li\u003e\n\u003cli\u003eKarakahya RH, Korkmaz M, Korkmaz H. \u003cem\u003eDecreased retinal nerve fiber and Choroidal thickness in chronic Rhinosinusitis.\u003c/em\u003e\u0026nbsp;\u003cem\u003eEur Arch Otorhinolaryngology. 2021;\u003c/em\u003e\u0026nbsp;278: 2863-2868.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"28\"\u003e\n\u003cli\u003eWellard J, Lee D, Valter K, Stone J\u003cem\u003e. Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia. \u003c/em\u003eVis Neurosc. 2005;22(4):501-507.doi:10.1017/S0952523805224112.\u003c/li\u003e\n\u003cli\u003e29. Lin PW, Lin HC, Friedman M, et al. \u003cem\u003eEffects of CPAP for patients with OSA on visual sensitivity and retinal thickness.\u003c/em\u003e\u003cem\u003eSleep Med\u003c/em\u003e. 2020;67:156-163. doi:10.1016/j.sleep.2019.10.019.\u003c/li\u003e\n\u003cli\u003eWagh V, Tidake PK, Aurangabadkar G. \u003cem\u003eThe Role of Optical Coherence Tomography to Measure Retinal Nerve Fiber Layer Thickness in Patients with Chronic Obstructive Pulmonary Disease\u003c/em\u003e. Cureus. 2022;14:e25517. doi: 10.7759/cureus.25517.\u003c/li\u003e\n\u003cli\u003eKocamış \u0026Ouml;, Zorlu D. \u003cem\u003eChoroid and retinal nerve fiber layer thickness in patients with chronic obstructive pulmonary disease exacerbation.\u003c/em\u003e J. Ophthalmol. 2018;2018:1201976. doi: 10.1155/2018/1201976.\u003c/li\u003e\n\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":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Optical coherence tomography angiography(OCTA), nasal polyposis, chronic rhinosinusitis","lastPublishedDoi":"10.21203/rs.3.rs-7032382/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7032382/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePURPOSE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aimed to evaluate optical coherence tomography angiography (OCTA) parameters in cases of chronic rhinosinusitis with nasal polyposis (CRSwNP), a common cause of chronic airway obstruction. These parameters were compared with those of healthy individuals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In this prospective study, 29 eyes of 29 participants with CRSwNP and 30 eyes of 30 individuals in the healthy control group were evaluated. Cases diagnosed with CRSwNP were defined as group 1, and the control group as group 2. Nasal polyps were documented and graded using nasal endoscopy. A complete ophthalmic examination and OCTA analysis were performed. Retinal vascular density (VD) in four quadrants of both the superficial and deep capillary plexuses were analyzed. Foveal avascular zone (FAZ) area, retinal nerve fiber layer (RNFL), and vessel diameter index (VDI) were measured and compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRetinal VD in the superficial plexus showed a significant difference between Group 1 and Group 2 only in the nasal quadrant (p=0.046). In the deep capillary plexus, differences were statistically significant in all quadrants (nasal, temporal, superior, and inferior), with lower vascular density in the CRSwNP group (p=0.008, p=0.037, p=0.011, and p=0.001, respectively).\u003c/p\u003e\n\u003cp\u003eIn Group 1, FAZ areas were 0.390±0.81 mm\u003csup\u003e2\u003c/sup\u003e and 0.395±0.96 mm\u003csup\u003e2\u003c/sup\u003e in the superficial and deep plexuses, respectively. In Group 2, superficial and deep FAZ areas were 0.337±0.12 mm\u003csup\u003e2\u003c/sup\u003e and 0.467±0.14 mm\u003csup\u003e2\u003c/sup\u003e, respectively. The difference in FAZ area in the superficial plexus was not statistically significant, but the difference in the deep plexus was (p=0.062 and p=0.022, respectively).\u003c/p\u003e\n\u003cp\u003eVDI was slightly higher in Group 1 than in Group 2, but the difference was not statistically significant in either the superficial or deep plexus (p=0.259 and p=0.200, respectively).\u003c/p\u003e\n\u003cp\u003eThe average macular RNFL thickness was 110.31±10.48 µm in Group1 and 93.22±11.50 µm in Group2, with the difference being statistically significant (p=0.007).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CRSwNP is an upper respiratory tract obstruction that can lead to hypoxia, increased small vessel resistance, dysregulation of nocturnal blood pressure, and alterations in perfusion pressure. The severity of nasal polyposis has been shown to significantly increase oxidative stress.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CRSwNP may also result in differences in some OCTA parameters when compared to healthy individuals. To the best of our knowledge, this is the first study to evaluate OCTA findings in patients with CRSwNP. Our findings suggest that repeated hypoxic cycles may affect OCTA parameters, particularly in the outer retinal layers and the RNFL.\u003c/p\u003e","manuscriptTitle":"OCT Angiography Parameters in Nasal Polyposis Associated with Chronic Rhinosinusitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 01:40:45","doi":"10.21203/rs.3.rs-7032382/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"70257099708913165219187080193460712822","date":"2026-02-04T10:20:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6038926324785441298622742238761706917","date":"2026-01-27T09:53:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-07T11:57:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"80957436787779961867539193976106221603","date":"2025-11-04T07:51:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-03T03:21:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-04T09:26:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-04T09:26:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2025-07-02T20:06:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d53d294b-b0b3-4602-b9fb-8be707249d5d","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-14T01:40:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-14 01:40:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7032382","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7032382","identity":"rs-7032382","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}