Choroidal vascularity index changes in chronic migraine patients

Choroidal vascularity index changes in chronic migraine patients | 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Research Article Choroidal vascularity index changes in chronic migraine patients Taha Sezer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1147803/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Migraine is a neurovascular disorder characterized by recurrent headaches. The relationship between migraine disease and the choroid, has been examined in an attempt to elucidate the underlying pathophysiological mechanisms. This study evaluated choroidal vascularity index (CVI) in chronic migraine patients. Methods: In this prospective study, we compared CT and CVI values of 36 chronic migraine patients (30 women and 6 men) during an attack-free period with those of 36 healthy individuals (30 women and 6 men) with no systemic or ocular disease, including headache. All patients underwent a detailed eye examination before enhanced depth imaging optical coherence tomography (EDI-OCT) imaging. Migraine patients were grouped as those with and without aura and were asked to rate their headache severity on visual analog scale (VAS; range 1-10) and estimate their monthly migraine frequency. Results: The mean subfoveal CT (SFCT) was 300.52 ± 88.30 µm in the migraine group and 262.85 ± 70.68 µm in the control group. The mean CVI was 71.8% ± 6.2% in the migraine group and 70.7% ± 5.3% in the control group. SFCT and CVI did not differ significantly between the migraine and control groups ( p >0.05). VAS pain score was 8.17 ± 0.33 in the migraine group and was not correlated with SFCT ( r =0, p =0.998) or CVI ( r =−0.06, p =0.731). The monthly migraine frequency was 5.60 ± 3.60 and was not correlated with SFCT ( r =−0.17, p =0.328) or CVI ( r =−0.06, p =0.731). Conclusion: CT and CVI showed no significant differences from controls in chronic migraine patients during an attack-free period. Choroidal vascularity index Choroidal thickness Migraine Optical coherence tomography Figures Figure 1 Figure 2 Introduction Migraine is a neurological disorder characterized by severe, recurrent unilateral headaches.[ 1 ] The diagnosis is based on the characteristics of the headache and associated neurological symptoms such as gastrointestinal and autonomic nervous system symptoms. These symptoms include photophobia, phonophobia, and vomiting, and the pain is usually aggravated by physical activity. One-third of migraine patients also experience transient visual, sensory, language, or motor disturbances before (or rarely, during) the headache, which are referred to as the aura.[ 2 ] The pathophysiology of migraine is not well understood and there is no consensus on existing theories. Vasogenic, neurogenic, and cortical spreading depression theories have been proposed to explain migraine pathophysiology.[ 3 ] The vasogenic theory attributes the headache to prolonged vasospasm followed by vasodilation,[ 4 , 5 ] whereas the neurogenic theory suggests that vascular changes in migraine occur as a result of neuronal dysfunction. In particular, the release of numerous vasogenic neuropeptides in the trigeminovascular region and the triggering of nociceptive impulses support that the pathophysiology of migraine may be of neurovascular origin.[ 6 ] Therefore, migraine is currently considered a neurovascular disease. The choroid receives most of the ocular blood flow, and understanding changes in its structure may provide insight into choroidal and ocular blood flow.[ 7 , 8 ] Choroidal imaging was generally performed with indocyanine green angiography (ICGA) and contact B-scan ultrasound (US) before the introduction of spectral domain optical coherence tomography (SD-OCT) into clinical use.[ 9 ] Although choroidal imaging with SD-OCT was inadequate at first, the enhanced depth imaging technique (EDI-OCT) uses longer wavelengths and has enabled detailed visualization of the luminal and stromal structures of the choroidal layer.[ 10 ] Most recently, the increasing clinical use of optical coherence tomography angiography (OCTA) has allowed non-invasive examination of the deep and superficial retinal, choriocapillaris, and choroidal circulation.[ 11 ] Numerous studies using EDI-OCT to identify vascular changes in the pathophysiology of migraine have investigated choroidal thickness (CT).[ 12 – 17 ] While measurement of CT may be helpful in clinical research, it is not a reliable parameter because it can be influenced by multiple factors, including diurnal variation, age, gender, and axial length. Therefore, research focus has shifted to choroidal vascularity index (CVI), which is not affected by physiological factors and is determined as the ratio of luminal area to total choroidal area using special software.[ 18 – 20 ] In this study, we aimed to examine differences in CT and CVI in patients with chronic migraine during an attack-free period compared to healthy controls. Materials And Methods Thirty-six migraine patients (30 women and 6 men) who were being followed due to chronic migraine and were referred from the neurology clinic of Düzce University and 36 control subjects (30 women and 6 men) with no ocular or systemic disease and no headache complaints were compared. The study was approved by the Düzce University Institutional Review Board and Ethics Committee and adhered to the Declaration of Helsinki. All participants provided informed consent to use their clinical data for this study. The migraine patients were grouped as those with and without aura according to the Headache International Society criteria.[ 21 ] They were asked to rate their headache pain severity using a visual analogue scale (between 0-10 points) and estimate their monthly headache frequency. All patients used nonsteroidal anti-inflammatory drugs for their migraine attacks. Patients with any disease that may affect choroidal flow (e.g., hypertension, diabetes mellitus, vasculitis, renal failure), smoking history, and use of drugs likely to affect CT (e.g., sildenafil, triptan, ergot alkaloids, antihistamines, decongestants) were not included in the study. Ophthalmologic Examination All participants in the control and migraine groups underwent a detailed ophthalmological examination by the same physician (M.B.). Best-corrected visual acuity (BCVA), fundoscopy, slit-lamp examination, and intraocular pressure measurement were performed in both groups. Exclusion criteria included spherical and cylindrical refractive errors greater than +/-3 diopters (D), amblyopia, retinal or choroidal pathology, intraocular surgery, and media opacity that would prevent OCT imaging. The right eyes of all participants were evaluated in the study. SD-OCT scans were performed at the same time of day (9:00-10:00 am) to minimize the effect of diurnal variation on the choroid.[ 22 ] Choroidal Thickness Measurement CT measurements were performed by the same experienced ophthalmologist (S.T.) using SD-OCT (Heidelberg Engineering, Heidelberg, Germany). A Spectralis OCT (Heidelberg Engineering) was used with a standardized imaging protocol. A 9-mm horizontal image centered on the fovea was obtained with an average of 100 B-scans in each section to improve the signal-to-noise ratio. Eye-tracking mode was also used. All subjects were examined with pupil dilation. CT was measured from the outer edge of the hyperreflective line corresponding to the retinal pigment epithelium (RPE) to the hyporeflective line corresponding to the choroidal-scleral interface. Measurements were made in three different regions, at the foveal center and 1000 µm nasal and temporal of the fovea. Choroid Vascularity Index Assessment Sonoda et al. used the image binarization technique to calculate CVI.[ 23 ] In this study we used the slightly modified technique described by Agrawal et al.[ 18 ] Open-source ImageJ software was used for image processing (version 1.47; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA; http://imagej.nih.gov/ij/ ). Briefly, 1 × 1 pixel EDI-OCT images were opened in ImageJ and the scale was set to 200 µm. A total choroidal area (TCA) 1.5 mm in width and centered on the fovea was selected and marked using with the manual plotting polygonal tool (Fig. 1). The upper border of the choroid was marked at the RPE and the lower border was marked at the choroid-sclera junction. The entire length of the OCT B-scan was used for analysis. Then the EDI-OCT B scan was converted to 8-bit images using the default setting. Niblack’s automated local threshold tool was applied to delineate the luminal area (LA) and stromal area (SA). The image was then converted back to an RGB (red, green, blue) image to enable computation of LA with the color threshold tool (Fig. 2). Lastly, CVI was calculated as the ratio of LA to TCA. CVI assessment was performed by the same physician who measured CT (S.T.). Statistical Analysis Statistical analysis was performed using SPSS software version 16.0 (SPSS, Inc., Chicago, IL, USA). The normality of data distributions was tested using Shapiro–Wilk test. Continuous variables were shown as median (min–max). Nominal data were analyzed by Pearson’s chi-square or Fisher’s exact test as appropriate. Differences between values in the three groups were analyzed using Kruskal-Wallis test. Mann–Whitney U test was used for pairwise comparisons of the groups. The correlation between SFCT and migraine variables was evaluated using Spearman’s correlation coefficient. Statistical significance was defined as p <0.05. Results Thirty-six right eyes of 36 participants in the migraine group (30 women, 6 men) and 36 right eyes of 36 participants in the control group (30 women, 6 men) were included in the study. The mean ages in the migraine and control groups were 34.7 ± 1.5 years (range 20-52) and 35.1 ± 1.4 years (range 23-51), respectively ( p =0.868). The groups were also similar in gender distribution. The migraine group included 5 patients who experienced migraine with aura and 31 patients with migraine without aura. BCVA was 0.00 logMAR (20/20 Snellen equivalent) in all eyes. The mean refractive error was -0.07 ± 0.72 D (range −2.25 to +1.50 D) in the migraine group and −0.15 ± 0.74 D (range −2.50 to +1.50 D) in the control group (Table 1). Table1. Demographic data of patients and controls Characteristics Migraine group (n= 36) Control group (n= 36) P value Age, years 34.7 ± 1.5 35.1 ± 1.4 0.868* Gender, n (male/female) 6/30 6/30 Refractive error, D -0.07 ± 0.72 -0.15 ± 0.74 0.677** VAS score (range) 8.17 ± 0.33 (1-10) Attacks per month (range) 5.60 ± 3.60 (1-14) * Student’s t-test ** Mann-Whitney U test VAS: Visual analogue scale SFCT was 300.52 ± 88.30 µm in the migraine group and 262.85 ± 70.68 µm in the control group. There were no significant differences between the groups in SFCT or CT 1000 µm temporal and nasal of the fovea ( p >0.05). The mean CVI was 71.8% ± 6.2% in the migraine group and 70.7% ± 5.3% in the control group ( p >0.05). Mean CVI, TCA, LA, and SA did not differ significantly between the migraine and control groups (Table 2 ). There was also no significant difference in CVI between migraine patients with and without aura ( p >0.05) (Table 3 ). Table 2 Comparison of choroidal parameters between patients with migraine and the control group Parameter Migraine group mean ± SD Control group mean ± SD P value Subfoveal CT (µm) 300.52 ± 88.30 262.85 ± 70.68 0.107** N1000 CT (µm) 295.44 ± 91.25 263.84 ± 78.54 0.205** T1000 CT (µm) 289.33 ± 93.48 263.92 ± 66.75 0.333** Total Choroidal Area (mm 2 ) 0.715 ± 0.219 0.689 ± 0.183 0.580* Luminal Area (mm 2 ) 0.516 ± 0.170 0.486 ± 0.130 0.395* Stromal Area (mm 2 ) 0.199 ± 0.067 0.203 ± 0.069 0.964** CVI (%) 71.8 ± 6.2 70.7 ± 5.3 0.316** * Student’s t-test ** Mann-Whitney U test CT: Choroidal thickness, N1000: 1000 µm nasal of fovea, T1000: 1000 µm temporal of fovea, CVI: Choroidal vascularity index, VAS: Visual analogue scale Table 3 Comparison of choroidal parameters in migraine patients with and without aura With aura (n=5) Without aura (n=31) P value Total Choroidal Area (mm 2 ) 0.778 ± 0.20 0.704 ± 0.22 0.481* Luminal Area (mm 2 ) 0.584 ± 0.18 0.505 ± 0.16 0.413* Stromal Area (mm 2 ) 0.193 ± 0.02 0.199 ± 0.07 0.765* CVI (%) 73.9 ± 7.5 71.5 ± 6 0.101** * Student’s t-test ** Mann-Whitney U test CVI: Choroidal vascularity index The mean VAS pain score in the migraine group was 8.17 ± 0.33 (range 1-10). VAS score was not correlated with SFCT or CVI ( r =0, p =0.998 and r =-0.06, p =0.731, respectively). The mean monthly migraine frequency was 5.60 ± 3.60 and there was also no correlation between migraine frequency and SFCT or CVI ( r =-0.17, p =0.328 and r =-0.06, p =0.731, respectively) (Table 4 ). Table 4 Correlation between VAS score, monthly migraine frequency, choroidal thickness, and CVI in migraine patients VAS score (range 1-10) Attacks per month (range 1-14) r p r p Subfoveal CT (µm) 0 0.998 -0.17 0.328 N1000 CT (µm) 0.06 0.733 -0.125 0.476 T1000 CT (µm) -0.039 0.826 -0.128 0.465 Total Choroidal Area (mm 2 ) 0.183 0.293 -0.046 0.792 Luminal Area (mm 2 ) 0.152 0.382 0.044 0.800 Stromal Area (mm 2 ) 0.328 0.054 0.017 0.923 CVI (%) -0.06 0.731 0.04 0.820 CT: Choroidal thickness, N1000: 1000 µm nasal of fovea, T1000: 1000 µm temporal of fovea, CVI: Choroidal vascularity index, VAS: Visual analogue scale Discussion In this study, we observed no significant differences in SFCT and CVI between chronic migraine patients during an attack-free period when compared with the control group. Zengin et al. found that the mean CT was thinner in newly diagnosed (at least 3 months) migraine patients than in the control group ( p =0.001). In the same study, they determined that CT decreased significantly in 5 patients during a migraine attack.[ 12 ] Reggio et al. also reported that CT was thinner in chronic migraine patients with and without aura compared to the control group ( p <0.0001 for both eyes).[ 14 ] Likewise, Karaca et al. found that SFCT was thinner in the attack-free period in migraine patients with and without aura compared to the control group ( p 0.05).[ 15 ] Contrary to these studies, Gunes et al. found that CT was thicker in chronic migraine patients compared to the control group ( p <0.001 for both eyes).[ 16 ] In their literature review, Ascado et al. summarized the different CT results obtained in migraine patients.[ 24 ] Therefore, a different parameter is needed due to the variable nature of CT. In our study, we determined that there was no statistically significant difference in CT and CVI between migraine patients and the normal healthy group. To the best of our knowledge, this is the first study evaluating the CVI in patients with chronic migraine. Temel et al. investigated CVI in newly diagnosed migraine patients and reported that CVI was significantly decreased in patients with migraine.[ 25 ] However, limitations of their study are that it included a relatively small sample size and they only excluded patients who used ergot alkaloids and triptans within 24 hours before examination. Ergot alkaloids and triptans induce arterial and venous vasoconstriction,[ 26 , 27 ] and the long-term effects of these drugs on CT are unknown. Therefore, the decrease in CVI may be related to the use of these drugs. Many studies have shown that CT is affected by various factors, especially certain drugs such as sildenafil and antihistamines, smoking, age, and the axial length of the eye.[ 28 – 31 ] While choroidal thinning is seen in choroidal dystrophies and AMD, thickening occurs in diseases such as Vogt-Koyanagi-Harada, central serous retinopathy, and polypoidal choroidal vasculopathy.[ 32 – 34 ] In addition, CT measurements may differ due to examiner bias and interobserver variation.[ 19 , 35 ] On the other hand, CVI gives more reliable information than CT because LA (vascular), SA (interstitial), and TCA are determined from EDI-OCT images by special software using the binarization method.[ 18 , 19 ] The rich vascular structure and changes in the connective tissue can be examined in more detail, providing more reliable data about the choroidal structure. For this reason, CVI is increasingly used instead of assessing choroidal structure only by its thickness. EDI-OCT is a non-invasive method that enables detailed visualization of the choroid.[ 10 ] Although ICGA is still considered the gold standard imaging modality in choroidal pathologies such as PCV, its clinical use is declining because of its invasiveness.[ 36 ] With EDI-OCT, however, the effects of intraocular pressure and perfusion changes on the choroid can be assessed instantly and non-invasively. OCTA imaging has also seen more widespread clinical use in recent years because it allows non-invasive visualization of retinal and choroidal blood flow. This method uses special software to detect the movement of red blood cells in the vasculature and display vascular flow.[ 11 ] Guler et al. used OCTA to examine differences in retinal, peripapillary, and choriocapillaris blood flow between 26 patients with migraine without aura and a healthy control group. They observed no significant difference between the two groups in terms of blood flow in the superficial or deep retina, choriocapillaris, or choroid (choroidal flow area was 9.64 ± 0.44 and 9.65 ± 0.21 mm 2 in the migraine and control groups, respectively, p =0.495).[ 37 ] Ozcift et al. examined optic disc perfusion, central macular perfusion, and central CT in 38 chronic migraine patients and reported no significant difference in perfusions or CT, although CT was negatively correlated with the duration of migraine disease ( r =−0.46, p =0.004).[ 38 ] OCT is excellent for visualizing the retinal and choroidal anatomy but provides no information about the vasculature or circulation.[ 39 ] The fact that we detected no statistically significant difference in CVI values between the two groups in our study is consistent with previous studies indicating no change in choroidal flow on OCTA. The inconsistency between OCTA and CT studies may also be due to the relative subjectivity of CT measurement. According to Guler et al., there was no significant difference in retinal and choroidal blood flow in migraine patients, and retinal blood flow was determined by the dynamics of the vascular microenvironment.[ 37 ] Rather than CT, more OCTA and CVI data are needed to explain pathophysiological mechanisms, especially in a disease of unclear pathophysiology such as migraine. Finally, we determined that mean VAS score (8.17 ± 0.33) and monthly attack frequency in the migraine group were not significantly correlated with CT or CVI. This is consistent with the results reported by Zengin et al., who observed no significant relationship between mean VAS score (5.55 ± 2.93) and CT.[ 12 ] However, Karaca et al. investigated the relationship between CT and VAS score, Migraine Disability Assessment Score, and Wong-Baker faces pain rating scale score and determined that CT moderately correlated with VAS score and Wong-Baker scores in patients with migraine without aura but not in patients with migraines with aura.[ 15 ] In this regard, it is clear that more studies are needed to understand the correlation between CT and different pain scores and migraine frequency. The present study has some limitations. One important limitation of our study is that changes in CVI were not evaluated during migraine attacks. Different results may be obtained during a migraine attack due to the activation of different pathophysiological mechanisms. Another limitation is the small number of patients included in the study. In addition, as in all CT studies, the manual determination of CT in our study is a limitation because manual segmentation remains a potential source of bias. Software-based automatic determination of CT is needed to eliminate this problem. In conclusion, the results of this study suggest that CT and CVI do not differ significantly in chronic migraine patients during an attack-free period compared to healthy controls. However, considering the complex pathophysiology of migraine disease, more studies are needed to understand the relationship between migraine and CT. Declarations Acknowledgments: None Statement and Declarations Compliance with ethical standards Conflict of interest Author Taha Sezer declares that he has no conflict of interest. Author Alper Aziz Hüdai Ayaslı declares that she has no conflict of interest. Author Bayram Meydan declares that he has no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by Duzce University Institutional Review Board. Informed consent Informed consent was obtained from all individual participants included in the study. References Tepper SJ, Rapoport A, Sheftell F (2001) The pathophysiology of migraine. Neurologist 7(5):279–286 Rasmussen BK, Olesen J (1992) Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia: an international journal of headache 12(4):221–228. discussion 186. Panconesi A, Bartolozzi ML, Guidi L (2009) Migraine pain: reflections against vasodilatation. J Headache Pain 10(5):317–325 Cole AJ, Aubé M (1990) Migraine with vasospasm and delayed intracerebral hemorrhage. 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Neuro-ophthalmology (Aeolus Press). 44:299–3065 Gürakar Özçift S, Aydın E, Eriş E (2021) Assessment of the choroidal thickness, central macular vascular and optic disk perfusion in migraine patients with optical coherence tomography angiography. Photodiagnosis Photodyn Ther 35:102397 Savastano MC, Lumbroso B, Rispoli M (2015) In vivo characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina (Philadelphia, Pa) 35(11):2196–2203 Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-1147803","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":88454991,"identity":"d315d28f-0189-44fc-a621-52f7b1c1ba30","order_by":0,"name":"Taha Sezer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYDCCAwwMzFAm4wMgwcNHWAszXAuzAUgLGyla2CTAJCEdfLfPH/xcUFMnJ9/e+6zya46dDBsD88NHN/BokTyXzCw949hhY8ae42a3ZbclAx3GZmycg0eLwRlmBmketgOJzRJpbLcltzEDtfCwSRPQwvyb519dfZv8M7ZiyW31RGlhk+ZtY07gkWBjY/y47TBhLZJnmM2sefsOG87gSWOWZtx2nIeNmYBf+M4wPr7N861OXr79GOPHn9uq7fnZmx8+xqcFBTDzgElilYMA4w9SVI+CUTAKRsGIAQDQ9j4xcN9FCwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4888-4293","institution":"Duzce University School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Taha","middleName":"","lastName":"Sezer","suffix":""}],"badges":[],"createdAt":"2021-12-07 07:06:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1147803/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1147803/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":18941211,"identity":"9cec9513-05a8-424f-a43f-11479b792bb5","added_by":"auto","created_at":"2022-03-07 17:11:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":265324,"visible":true,"origin":"","legend":"\u003cp\u003eA width of 1.5 mm centered at the fovea selected by manual plotting polygonal tool.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-1147803/v1/ba4ec7f2e04d8dd54043e1da.png"},{"id":18941210,"identity":"277e264b-c307-4a65-9d42-3be7086b8155","added_by":"auto","created_at":"2022-03-07 17:11:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56548,"visible":true,"origin":"","legend":"\u003cp\u003eSuperimposed binarized image showing segmentation of the choroidal luminal and stromal structures.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-1147803/v1/d1d273c22d26ebe40260c188.png"},{"id":20462875,"identity":"88f214cc-a2b1-4fcc-8b50-bebfd506189c","added_by":"auto","created_at":"2022-04-18 15:58:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":745685,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1147803/v1/dff216cb-9ff7-4936-8438-dd5dba1621de.pdf"}],"financialInterests":"","formattedTitle":"Choroidal vascularity index changes in chronic migraine patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMigraine is a neurological disorder characterized by severe, recurrent unilateral headaches.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The diagnosis is based on the characteristics of the headache and associated neurological symptoms such as gastrointestinal and autonomic nervous system symptoms. These symptoms include photophobia, phonophobia, and vomiting, and the pain is usually aggravated by physical activity. One-third of migraine patients also experience transient visual, sensory, language, or motor disturbances before (or rarely, during) the headache, which are referred to as the aura.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe pathophysiology of migraine is not well understood and there is no consensus on existing theories. Vasogenic, neurogenic, and cortical spreading depression theories have been proposed to explain migraine pathophysiology.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The vasogenic theory attributes the headache to prolonged vasospasm followed by vasodilation,[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] whereas the neurogenic theory suggests that vascular changes in migraine occur as a result of neuronal dysfunction. In particular, the release of numerous vasogenic neuropeptides in the trigeminovascular region and the triggering of nociceptive impulses support that the pathophysiology of migraine may be of neurovascular origin.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Therefore, migraine is currently considered a neurovascular disease.\u003c/p\u003e \u003cp\u003eThe choroid receives most of the ocular blood flow, and understanding changes in its structure may provide insight into choroidal and ocular blood flow.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Choroidal imaging was generally performed with indocyanine green angiography (ICGA) and contact B-scan ultrasound (US) before the introduction of spectral domain optical coherence tomography (SD-OCT) into clinical use.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Although choroidal imaging with SD-OCT was inadequate at first, the enhanced depth imaging technique (EDI-OCT) uses longer wavelengths and has enabled detailed visualization of the luminal and stromal structures of the choroidal layer.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Most recently, the increasing clinical use of optical coherence tomography angiography (OCTA) has allowed non-invasive examination of the deep and superficial retinal, choriocapillaris, and choroidal circulation.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eNumerous studies using EDI-OCT to identify vascular changes in the pathophysiology of migraine have investigated choroidal thickness (CT).[\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] While measurement of CT may be helpful in clinical research, it is not a reliable parameter because it can be influenced by multiple factors, including diurnal variation, age, gender, and axial length. Therefore, research focus has shifted to choroidal vascularity index (CVI), which is not affected by physiological factors and is determined as the ratio of luminal area to total choroidal area using special software.[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] In this study, we aimed to examine differences in CT and CVI in patients with chronic migraine during an attack-free period compared to healthy controls.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThirty-six migraine patients (30 women and 6 men) who were being followed due to chronic migraine and were referred from the neurology clinic of D\u0026uuml;zce University and 36 control subjects (30 women and 6 men) with no ocular or systemic disease and no headache complaints were compared. The study was approved by the D\u0026uuml;zce University Institutional Review Board and Ethics Committee and adhered to the Declaration of Helsinki. All participants provided informed consent to use their clinical data for this study.\u003c/p\u003e \u003cp\u003eThe migraine patients were grouped as those with and without aura according to the Headache International Society criteria.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] They were asked to rate their headache pain severity using a visual analogue scale (between 0-10 points) and estimate their monthly headache frequency. All patients used nonsteroidal anti-inflammatory drugs for their migraine attacks.\u003c/p\u003e \u003cp\u003ePatients with any disease that may affect choroidal flow (e.g., hypertension, diabetes mellitus, vasculitis, renal failure), smoking history, and use of drugs likely to affect CT (e.g., sildenafil, triptan, ergot alkaloids, antihistamines, decongestants) were not included in the study.\u003c/p\u003e\n\u003ch2\u003eOphthalmologic Examination\u003c/h2\u003e\n\u003cp\u003eAll participants in the control and migraine groups underwent a detailed ophthalmological examination by the same physician (M.B.). Best-corrected visual acuity (BCVA), fundoscopy, slit-lamp examination, and intraocular pressure measurement were performed in both groups.\u003c/p\u003e \u003cp\u003eExclusion criteria included spherical and cylindrical refractive errors greater than +/-3 diopters (D), amblyopia, retinal or choroidal pathology, intraocular surgery, and media opacity that would prevent OCT imaging. The right eyes of all participants were evaluated in the study. SD-OCT scans were performed at the same time of day (9:00-10:00 am) to minimize the effect of diurnal variation on the choroid.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\n\u003ch2\u003eChoroidal Thickness Measurement\u003c/h2\u003e\n\u003cp\u003eCT measurements were performed by the same experienced ophthalmologist (S.T.) using SD-OCT (Heidelberg Engineering, Heidelberg, Germany). A Spectralis OCT (Heidelberg Engineering) was used with a standardized imaging protocol. A 9-mm horizontal image centered on the fovea was obtained with an average of 100 B-scans in each section to improve the signal-to-noise ratio. Eye-tracking mode was also used. All subjects were examined with pupil dilation. CT was measured from the outer edge of the hyperreflective line corresponding to the retinal pigment epithelium (RPE) to the hyporeflective line corresponding to the choroidal-scleral interface. Measurements were made in three different regions, at the foveal center and 1000 \u0026micro;m nasal and temporal of the fovea.\u003c/p\u003e\n\u003ch2\u003eChoroid Vascularity Index Assessment\u003c/h2\u003e\n\u003cp\u003eSonoda et al. used the image binarization technique to calculate CVI.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] In this study we used the slightly modified technique described by Agrawal et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Open-source ImageJ software was used for image processing (version 1.47; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://imagej.nih.gov/ij/\u003c/span\u003e\u003c/span\u003e). Briefly, 1 \u0026times; 1 pixel EDI-OCT images were opened in ImageJ and the scale was set to 200 \u0026micro;m. A total choroidal area (TCA) 1.5 mm in width and centered on the fovea was selected and marked using with the manual plotting polygonal tool (Fig.\u0026nbsp;1). The upper border of the choroid was marked at the RPE and the lower border was marked at the choroid-sclera junction. The entire length of the OCT B-scan was used for analysis. Then the EDI-OCT B scan was converted to 8-bit images using the default setting. Niblack\u0026rsquo;s automated local threshold tool was applied to delineate the luminal area (LA) and stromal area (SA). The image was then converted back to an RGB (red, green, blue) image to enable computation of LA with the color threshold tool (Fig.\u0026nbsp;2). Lastly, CVI was calculated as the ratio of LA to TCA. CVI assessment was performed by the same physician who measured CT (S.T.).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS software version 16.0 (SPSS, Inc., Chicago, IL, USA). The normality of data distributions was tested using Shapiro\u0026ndash;Wilk test. Continuous variables were shown as median (min\u0026ndash;max). Nominal data were analyzed by Pearson\u0026rsquo;s chi-square or Fisher\u0026rsquo;s exact test as appropriate. Differences between values in the three groups were analyzed using Kruskal-Wallis test. Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test was used for pairwise comparisons of the groups. The correlation between SFCT and migraine variables was evaluated using Spearman\u0026rsquo;s correlation coefficient. Statistical significance was defined as \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThirty-six right eyes of 36 participants in the migraine group (30 women, 6 men) and 36 right eyes of 36 participants in the control group (30 women, 6 men) were included in the study. The mean ages in the migraine and control groups were 34.7 \u0026plusmn; 1.5 years (range 20-52) and 35.1 \u0026plusmn; 1.4 years (range 23-51), respectively (\u003cem\u003ep\u003c/em\u003e=0.868). The groups were also similar in gender distribution. The migraine group included 5 patients who experienced migraine with aura and 31 patients with migraine without aura. BCVA was 0.00 logMAR (20/20 Snellen equivalent) in all eyes. The mean refractive error was -0.07 \u0026plusmn; 0.72 D (range \u0026minus;2.25 to +1.50 D) in the migraine group and \u0026minus;0.15 \u0026plusmn; 0.74 D (range \u0026minus;2.50 to +1.50 D) in the control group (Table 1).\u003c/p\u003e\u003cp\u003eTable1. Demographic data of patients and controls\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003eMigraine group\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n= 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\n \u003cp\u003eControl group\u003c/p\u003e\n \u003cp\u003e(n= 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003e34.7 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\n \u003cp\u003e35.1 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\n \u003cp\u003e0.868*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eGender, n (male/female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003e6/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\n \u003cp\u003e6/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eRefractive error, D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003e-0.07 \u0026plusmn; 0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\n \u003cp\u003e-0.15 \u0026plusmn; 0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\n \u003cp\u003e0.677**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eVAS score (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003e8.17 \u0026plusmn; 0.33 (1-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"32.586558044806516%\"\u003e\n \u003cp\u003eAttacks per month (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"30.75356415478615%\"\u003e\n \u003cp\u003e5.60 \u0026plusmn; 3.60 (1-14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"25.05091649694501%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.608961303462321%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" width=\"100%\"\u003e\n \u003cp\u003e* Student\u0026rsquo;s t-test\u003c/p\u003e\n \u003cp\u003e** Mann-Whitney U test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eVAS: Visual analogue scale\u003c/p\u003e \u003cp\u003eSFCT was 300.52 \u0026plusmn; 88.30 \u0026micro;m in the migraine group and 262.85 \u0026plusmn; 70.68 \u0026micro;m in the control group. There were no significant differences between the groups in SFCT or CT 1000 \u0026micro;m temporal and nasal of the fovea (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05). The mean CVI was 71.8% \u0026plusmn; 6.2% in the migraine group and 70.7% \u0026plusmn; 5.3% in the control group (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05). Mean CVI, TCA, LA, and SA did not differ significantly between the migraine and control groups (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There was also no significant difference in CVI between migraine patients with and without aura (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of choroidal parameters between patients with migraine and the control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMigraine group\u003c/p\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubfoveal CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300.52 \u0026plusmn; 88.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e262.85 \u0026plusmn; 70.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.107**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1000 CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e295.44 \u0026plusmn; 91.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e263.84 \u0026plusmn; 78.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.205**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1000 CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289.33 \u0026plusmn; 93.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e263.92 \u0026plusmn; 66.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.333**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Choroidal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.715 \u0026plusmn; 0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.689 \u0026plusmn; 0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.580*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuminal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.516 \u0026plusmn; 0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.486 \u0026plusmn; 0.130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.395*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStromal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.199 \u0026plusmn; 0.067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.203 \u0026plusmn; 0.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.964**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.8 \u0026plusmn; 6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.7 \u0026plusmn; 5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.316**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e* Student\u0026rsquo;s t-test\u003c/p\u003e \u003cp\u003e** Mann-Whitney U test\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCT: Choroidal thickness, N1000: 1000 \u0026micro;m nasal of fovea, T1000: 1000 \u0026micro;m temporal of fovea, CVI: Choroidal vascularity index, VAS: Visual analogue scale\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of choroidal parameters in migraine patients with and without aura\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith aura\u003c/p\u003e \u003cp\u003e(n=5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout aura\u003c/p\u003e \u003cp\u003e(n=31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Choroidal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.778 \u0026plusmn; 0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.704 \u0026plusmn; 0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.481*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuminal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.584 \u0026plusmn; 0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.505 \u0026plusmn; 0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.413*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStromal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.193 \u0026plusmn; 0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.199 \u0026plusmn; 0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.765*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.9 \u0026plusmn; 7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.5 \u0026plusmn; 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.101**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e* Student\u0026rsquo;s t-test\u003c/p\u003e \u003cp\u003e** Mann-Whitney U test\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCVI: Choroidal vascularity index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean VAS pain score in the migraine group was 8.17 \u0026plusmn; 0.33 (range 1-10). VAS score was not correlated with SFCT or CVI (\u003cem\u003er\u003c/em\u003e=0, \u003cem\u003ep\u003c/em\u003e=0.998 and \u003cem\u003er\u003c/em\u003e=-0.06, \u003cem\u003ep\u003c/em\u003e=0.731, respectively). The mean monthly migraine frequency was 5.60 \u0026plusmn; 3.60 and there was also no correlation between migraine frequency and SFCT or CVI (\u003cem\u003er\u003c/em\u003e=-0.17, \u003cem\u003ep\u003c/em\u003e=0.328 and \u003cem\u003er\u003c/em\u003e=-0.06, \u003cem\u003ep\u003c/em\u003e=0.731, respectively) (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between VAS score, monthly migraine frequency, choroidal thickness, and CVI in migraine patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eVAS score\u003c/p\u003e \u003cp\u003e(range 1-10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eAttacks per month\u003c/p\u003e \u003cp\u003e(range 1-14)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003er\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubfoveal CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1000 CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.476\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1000 CT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Choroidal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.792\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuminal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStromal Area (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.820\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCT: Choroidal thickness, N1000: 1000 \u0026micro;m nasal of fovea, T1000: 1000 \u0026micro;m temporal of fovea, CVI: Choroidal vascularity index, VAS: Visual analogue scale\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we observed no significant differences in SFCT and CVI between chronic migraine patients during an attack-free period when compared with the control group. Zengin et al. found that the mean CT was thinner in newly diagnosed (at least 3 months) migraine patients than in the control group (\u003cem\u003ep\u003c/em\u003e=0.001). In the same study, they determined that CT decreased significantly in 5 patients during a migraine attack.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Reggio et al. also reported that CT was thinner in chronic migraine patients with and without aura compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.0001 for both eyes).[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Likewise, Karaca et al. found that SFCT was thinner in the attack-free period in migraine patients with and without aura compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05). However, CT was similar at all measured points between the migraine subgroups with and without aura (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05).[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Contrary to these studies, Gunes et al. found that CT was thicker in chronic migraine patients compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001 for both eyes).[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] In their literature review, Ascado et al. summarized the different CT results obtained in migraine patients.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Therefore, a different parameter is needed due to the variable nature of CT. In our study, we determined that there was no statistically significant difference in CT and CVI between migraine patients and the normal healthy group. To the best of our knowledge, this is the first study evaluating the CVI in patients with chronic migraine.\u003c/p\u003e \u003cp\u003eTemel et al. investigated CVI in newly diagnosed migraine patients and reported that CVI was significantly decreased in patients with migraine.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] However, limitations of their study are that it included a relatively small sample size and they only excluded patients who used ergot alkaloids and triptans within 24 hours before examination. Ergot alkaloids and triptans induce arterial and venous vasoconstriction,[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and the long-term effects of these drugs on CT are unknown. Therefore, the decrease in CVI may be related to the use of these drugs.\u003c/p\u003e \u003cp\u003eMany studies have shown that CT is affected by various factors, especially certain drugs such as sildenafil and antihistamines, smoking, age, and the axial length of the eye.[\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] While choroidal thinning is seen in choroidal dystrophies and AMD, thickening occurs in diseases such as Vogt-Koyanagi-Harada, central serous retinopathy, and polypoidal choroidal vasculopathy.[\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] In addition, CT measurements may differ due to examiner bias and interobserver variation.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] On the other hand, CVI gives more reliable information than CT because LA (vascular), SA (interstitial), and TCA are determined from EDI-OCT images by special software using the binarization method.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] The rich vascular structure and changes in the connective tissue can be examined in more detail, providing more reliable data about the choroidal structure. For this reason, CVI is increasingly used instead of assessing choroidal structure only by its thickness.\u003c/p\u003e \u003cp\u003eEDI-OCT is a non-invasive method that enables detailed visualization of the choroid.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Although ICGA is still considered the gold standard imaging modality in choroidal pathologies such as PCV, its clinical use is declining because of its invasiveness.[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] With EDI-OCT, however, the effects of intraocular pressure and perfusion changes on the choroid can be assessed instantly and non-invasively. OCTA imaging has also seen more widespread clinical use in recent years because it allows non-invasive visualization of retinal and choroidal blood flow. This method uses special software to detect the movement of red blood cells in the vasculature and display vascular flow.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Guler et al. used OCTA to examine differences in retinal, peripapillary, and choriocapillaris blood flow between 26 patients with migraine without aura and a healthy control group. They observed no significant difference between the two groups in terms of blood flow in the superficial or deep retina, choriocapillaris, or choroid (choroidal flow area was 9.64 \u0026plusmn; 0.44 and 9.65 \u0026plusmn; 0.21 mm\u003csup\u003e2\u003c/sup\u003e in the migraine and control groups, respectively, \u003cem\u003ep\u003c/em\u003e=0.495).[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] Ozcift et al. examined optic disc perfusion, central macular perfusion, and central CT in 38 chronic migraine patients and reported no significant difference in perfusions or CT, although CT was negatively correlated with the duration of migraine disease (\u003cem\u003er\u003c/em\u003e=\u0026minus;0.46, \u003cem\u003ep\u003c/em\u003e=0.004).[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOCT is excellent for visualizing the retinal and choroidal anatomy but provides no information about the vasculature or circulation.[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] The fact that we detected no statistically significant difference in CVI values between the two groups in our study is consistent with previous studies indicating no change in choroidal flow on OCTA. The inconsistency between OCTA and CT studies may also be due to the relative subjectivity of CT measurement. According to Guler et al., there was no significant difference in retinal and choroidal blood flow in migraine patients, and retinal blood flow was determined by the dynamics of the vascular microenvironment.[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] Rather than CT, more OCTA and CVI data are needed to explain pathophysiological mechanisms, especially in a disease of unclear pathophysiology such as migraine.\u003c/p\u003e \u003cp\u003eFinally, we determined that mean VAS score (8.17 \u0026plusmn; 0.33) and monthly attack frequency in the migraine group were not significantly correlated with CT or CVI. This is consistent with the results reported by Zengin et al., who observed no significant relationship between mean VAS score (5.55 \u0026plusmn; 2.93) and CT.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] However, Karaca et al. investigated the relationship between CT and VAS score, Migraine Disability Assessment Score, and Wong-Baker faces pain rating scale score and determined that CT moderately correlated with VAS score and Wong-Baker scores in patients with migraine without aura but not in patients with migraines with aura.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] In this regard, it is clear that more studies are needed to understand the correlation between CT and different pain scores and migraine frequency.\u003c/p\u003e \u003cp\u003eThe present study has some limitations. One important limitation of our study is that changes in CVI were not evaluated during migraine attacks. Different results may be obtained during a migraine attack due to the activation of different pathophysiological mechanisms. Another limitation is the small number of patients included in the study. In addition, as in all CT studies, the manual determination of CT in our study is a limitation because manual segmentation remains a potential source of bias. Software-based automatic determination of CT is needed to eliminate this problem.\u003c/p\u003e \u003cp\u003eIn conclusion, the results of this study suggest that CT and CVI do not differ significantly in chronic migraine patients during an attack-free period compared to healthy controls. However, considering the complex pathophysiology of migraine disease, more studies are needed to understand the relationship between migraine and CT.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement and Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with ethical standards\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e Author Taha Sezer declares that he has no conflict of interest. Author\u0026nbsp;Alper Aziz H\u0026uuml;dai Ayaslı\u0026nbsp;declares that she has no conflict of interest. Author\u0026nbsp;Bayram Meydan\u0026nbsp;declares that he has no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by\u0026nbsp;Duzce University\u0026nbsp;Institutional Review Board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTepper SJ, Rapoport A, Sheftell F (2001) The pathophysiology of migraine. 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Arch Ophthalmol 116(4):455\u0026ndash;463\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSezer T, Altınışık M, Koytak İA, \u0026Ouml;zdemir MH (2016) The Choroid and Optical Coherence Tomography. Turk J Ophthalmol 46(1):30\u0026ndash;37\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G (2018) Optical coherence tomography angiography. Prog Retin Eye Res 64:1\u0026ndash;55\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZengin MO, Elmas Z, Cinar E, Kucukerdonmez C (2015) Choroidal thickness changes in patients with migraine. Acta Neurol Belg 115(1):33\u0026ndash;37\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaralezli A, Celik G, Koktekir BE, Kucukerdonmez C (2015) Evaluation of choroidal thickness using spectral-domain optical coherence tomography in patients with migraine: a comparative study. 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Neuro-ophthalmology (Aeolus Press). 44:299\u0026ndash;3065\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026uuml;rakar \u0026Ouml;z\u0026ccedil;ift S, Aydın E, Eriş E (2021) Assessment of the choroidal thickness, central macular vascular and optic disk perfusion in migraine patients with optical coherence tomography angiography. Photodiagnosis Photodyn Ther 35:102397\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSavastano MC, Lumbroso B, Rispoli M (2015) In vivo characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina (Philadelphia, Pa) 35(11):2196\u0026ndash;2203\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Choroidal vascularity index, Choroidal thickness, Migraine, Optical coherence tomography","lastPublishedDoi":"10.21203/rs.3.rs-1147803/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1147803/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose:\u003cstrong\u003e \u003c/strong\u003eMigraine is a neurovascular disorder characterized by recurrent headaches. The relationship between migraine disease and the choroid, has been examined in an attempt to elucidate the underlying pathophysiological mechanisms. This study evaluated choroidal vascularity index (CVI) in chronic migraine patients.\u003c/p\u003e\u003cp\u003eMethods:\u003cstrong\u003e \u003c/strong\u003eIn this prospective study, we compared CT and CVI values of 36 chronic migraine patients (30 women and 6 men) during an attack-free period with those of 36 healthy individuals (30 women and 6 men) with no systemic or ocular disease, including headache. All patients underwent a detailed eye examination before enhanced depth imaging optical coherence tomography (EDI-OCT) imaging. Migraine patients were grouped as those with and without aura and were asked to rate their headache severity on visual analog scale (VAS; range 1-10) and estimate their monthly migraine frequency.\u003c/p\u003e\u003cp\u003eResults:\u003cstrong\u003e \u003c/strong\u003eThe mean subfoveal CT (SFCT) was 300.52 ± 88.30 µm in the migraine group and 262.85 ± 70.68 µm in the control group. The mean CVI was 71.8% ± 6.2% in the migraine group and 70.7% ± 5.3% in the control group. SFCT and CVI did not differ significantly between the migraine and control groups (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05). VAS pain score was 8.17 ± 0.33 in the migraine group and was not correlated with SFCT (\u003cem\u003er\u003c/em\u003e=0, \u003cem\u003ep\u003c/em\u003e=0.998) or CVI (\u003cem\u003er\u003c/em\u003e=−0.06, \u003cem\u003ep\u003c/em\u003e=0.731). The monthly migraine frequency was 5.60 ± 3.60 and was not correlated with SFCT (\u003cem\u003er\u003c/em\u003e=−0.17, \u003cem\u003ep\u003c/em\u003e=0.328) or CVI (\u003cem\u003er\u003c/em\u003e=−0.06, \u003cem\u003ep\u003c/em\u003e=0.731).\u003c/p\u003e\u003cp\u003eConclusion:\u003cstrong\u003e \u003c/strong\u003eCT and CVI showed no significant differences from controls in chronic migraine patients during an attack-free period.\u003c/p\u003e","manuscriptTitle":"Choroidal vascularity index changes in chronic migraine patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-07 17:11:06","doi":"10.21203/rs.3.rs-1147803/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3375b180-2288-4f17-9be6-3314990cdd9f","owner":[],"postedDate":"March 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-04-18T15:58:02+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-07 17:11:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1147803","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1147803","identity":"rs-1147803","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}