Multimodal OCT and OCT-Angiography Findings in Behçet Disease: Evidence of Persistent Microvascular Alterations and Association with Fluorescein Angiography

Multimodal OCT and OCT-Angiography Findings in Behçet Disease: Evidence of Persistent Microvascular Alterations and Association with Fluorescein Angiography | 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 Multimodal OCT and OCT-Angiography Findings in Behçet Disease: Evidence of Persistent Microvascular Alterations and Association with Fluorescein Angiography Şerife Nur Çiftci, Günhal ŞATIRTAV, Adem Küçük, Mustafa Oğul This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9581546/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 To evaluate macular, peripapillary, and choroidal microvascular alterations in patients with Behcet’s disease (BD) using optical coherence tomography (OCT), OCT angiography (OCT-A) and enhanced depth imaging (EDI-OCT), and to determine the relationship between these alterations and fluorescein angiography (FA) findings. Methods This retrospective study included 119 participants: 37 patients with Behçet uveitis (BU), 42 patients with nonocular BD and 40 healthy controls. OCT, OCT-A, and EDI-OCT were performed on all the participants. In the BU group, measurements were obtained during clinical remission and analyzed in relation to FA images acquired at the initial diagnosis. Results The foveal avascular zone (FAZ) area was significantly larger in eyes with BU than in those with nonocular BD and healthy controls (p = 0.001). Capillary vessel density (CVD) in both the superficial and deep capillary plexuses was significantly reduced in BU eyes (p < 0.001 for both). Subfoveal choroidal thickness (ChT) was significantly greater in the BU group than in the other groups (p < 0.001). FA scores demonstrated a moderate positive correlation with the FAZ area (r = 0.449, p < 0.001) and a negative correlation with superficial and deep CVD parameters. Central macular thickness was significantly lower in the BU group (p = 0.025). Conclusion OCT-A and EDI-OCT demonstrated persistent retinal and choroidal microvascular alterations in patients with BU, even during remission. These noninvasive parameters were significantly associated with baseline FA findings, indicating that the severity of the initial inflammatory insult may play a significant role in long-term structural damage. These observations highlight the potential importance of early and effective management of initial inflammatory episodes to minimize irreversible vascular loss. Behçet Disease Behçet Uveitis Optical Coherence Tomography Angiography Fundus Fluorescein Angiography Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Behcet’s disease (BD) is a chronic, relapsing, multisystemic disorder characterized by inflammatory systemic occlusive vasculitis ( 1 – 3 ). It is a worldwide disease but is more frequent in Mediterranean countries and Japan ( 1 , 2 ). BD accounts for approximately 24.9% of noninfectious uveitis cases in the Turkish population, and serves the primary etiology ( 4 ). Ocular involvement occurs in approximately 50–70% of patients with BD ( 5 ). This usually manifests as multiple episodes of nongranulomatous, necrotizing inflammation in the posterior segment, which are explosive in nature and responsive to steroids. Anterior uveitis can present as nongranulomatous in nature, affecting up to 80% of cases, with several cases being symptomatic with transitory hypopyon ( 5 ). Patients may also experience conjunctivitis, episcleritis, and keratitis. However, posterior uveitis is vastly detrimental to vision as a result of recurrent vascular occlusions, retinal hemorrhages and exudates, vascular sheathing, cystoid macular edema, retinal infiltrates, vitritis, and occasionally, optic neuropathy ( 1 , 2 , 5 ). Fundus fluorescein angiography (FA) is the gold standard method for the diagnosis and follow-up of Behcet’s vasculitis. It is a crucial imaging method for determining the severity of inflammation and monitoring the treatment response in cases of posterior involvement ( 6 ). Optical coherence tomography angiography (OCTA) is a noninvasive, repeatable, high-resolution imaging technique that provides information about foveal and peripapillary microvascular structures without the need for contrast agent injection. Careful interpretation of optic coherence tomography (OCT) and OCTA images can aid in follow-up, clinical outcome prediction, and differential diagnosis of uveitis( 7 – 9 ). The first assessment of OCTA in active BU was performed by Khairallah in 48 eyes of 25 patients and revealed a significant effect on the deep retinal capillary plexus compared with the superficial retinal capillary plexus ( 10 ). Numerous subsequent investigations have shown decreased vascular density in Behçet uveitis patients during the active and inactive periods by comparing parafoveal and peripapillary microvascular alterations with those in healthy subjects ( 10 – 14 ). The primary objective of this study was to investigate whether the persistent retinal and choroidal microvascular alterations observed during clinical remission reflect the initial inflammatory burden documented at diagnosis and to evaluate the potential of these structural parameters as objective, noninvasive biomarkers of the cumulative ocular damage sustained in Behçet Uveitis patients. METHODS Study Design and Participants This retrospective study was conducted at the Department of Ophthalmology, Necmettin Erbakan University between February 2021 and February 2022. The study protocol was approved by the Ethics Committee of Necmettin Erbakan University (Approval No. 2022/3687) and adhered to the principles of the Declaration of Helsinki. A total of 119 participants were included and divided into three groups: 37 patients with Behçet uveitis (BU) presenting with posterior uveitis or panuveitis, 42 patients with Behçet disease (BD) without ocular involvement, and 40 age- and sex-matched healthy controls. In the BU group, the more severely affected eye was included for analysis, whereas the right eye was analyzed in the nonocular BD and healthy groups. Healthy controls had no history of systemic disease, chronic ocular pathology, or ocular surgery, and had spherical and cylindrical refractive errors within the − 3.0 to + 3.0 diopter range. All participants underwent a comprehensive ophthalmological evaluation performed by a single experienced ophthalmologist. The evaluations included best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, intraocular pressure measurement, gonioscopy, and dilated fundus examination. BCVA values were then transformed to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis since it was originally taken with Snellen notation. The patients with BU were additionally evaluated according to the number of relapses, disease duration, t interval between the active phase (during which FA scores were obtained) and the remission phase (during which other parameters were measured), and treatment regimens used. OCT and OCT angiography imaging Spectral-domain optical coherence tomography (SD-OCT), enhanced depth imaging OCT (EDI-OCT), and retinal nerve fiber layer (RNFL) thickness measurements were performed in all participants using a Heidelberg Spectralis OCT system (Heidelberg Engineering, Germany). Central macular thickness was measured within the central 1-mm diameter circle of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. OCT angiography (OCT-A) imaging was performed using the AngioVue OCT-A system (RTVue XR; Optovue Inc., Fremont, CA, USA) with software version 2018.1.0.37. The device software automatically segmented en face images of the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retinal layer, and choriocapillaris into four different layers. 6*6 mm macular and 4.5*4.5 mm optic disc OCTA images obtained with AngioVue technology were analyzed. Foveal (1.0-mm diameter) and parafoveal (1.0–3.0 mm annulus) regions were analyzed according to the ETDRS grid. The foveal avascular zone (FAZ) area (µm²) and peripapillary vessel density within a 750-µm annulus were automatically calculated using the software (Fig. 1 ). OCTA images use the inner limiting membrane, outer border of the inner plexiform layer, outer border of the outer plexiform layer, and Bruch's membrane as landmarks. The automated layer segmentation provided by the device software was carefully inspected in each scan by two experienced graders, and scans with segmentation errors were excluded from the analysis. Images with significant projection or motion artifacts were excluded following a manual review. Only images with a signal strength and quality of at least 7/10 were included. Fluorescein Angiography Assessment In patients with BU, fluorescein angiography (FA) images obtained at the time of initial diagnosis were retrospectively reviewed. FA was performed using the Heidelberg HRA Spectralis system (Heidelberg Engineering, Germany) (Fig. 2 ). Early- and late-phase (5–8 min) images of the posterior pole and peripheral quadrants were evaluated and scored according to the Angiography Scoring for Uveitis Working Group (ASUWOG) system ( 15 ). The proposed scoring system for reference during the FA and the total maximum score for each of the angiographic signs are given in Table I. Optic disc hyperfluorescence is scored from 1 to 3; target-like staining of the disc ,s given a score of 1, while leakage at the disc with blurring of the disc margins is given a score of 3. Neovascularization of the disc (NVD) receives an additional score of 2, whether it arises as a sequela of extensive retinal ischemia or severe intraocular inflammation does not matter. Macular edema was graded from 1 to 4, with pooling of dye in the cystic spaces at the macula receiving a score of 4. The staining or leakage of retinal vessel walls may be focal/multifocal or diffuse along the course of the vessels. This scoring was performed for the posterior pole arcades. For other parts of the retinal vascular tree, involvement was scored as absent or present, with 1 for each quadrant exhibiting the finding to any degree. However capillary leakage is considered a more specific indicator of inflammation, and we chose to score this finding to reflect the importance of this variable instead of simply documenting its presence or absence. Retinal capillary nonperfusion is graded according to the number of quadrants involved and is not considered a direct measure of inflammation; any area of capillary nonperfusion situated in the posterior pole is given in an additional score of 1, irrespective of whether there is advanced enlargement of the central avascular zone. Pinpoint leakage and subretinal pooling of the dye may be focal or extensive. The maximum total score for FA is 40 ( 16 ). The FAs were scored by two masked interpreters, and in cases of disagreement, the final score was obtained through discussion. Macular, peripapillary, and choroidal parameters obtained using OCT, OCT-A, and EDI-OCT were quantitatively compared among patients with Behçet’s uveitis, patients with Behçet’s disease without ocular involvement, and healthy controls. In addition, in the Behçet’s uveitis group, these parameters were analyzed in relation to fluorescein angiography scores obtained at the time of diagnosis. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 25.0 software. In the descriptive analyses, the frequency data were are presented as counts (n) and percentages (%), whereas the numerical data are expressed as the mean ± standard deviation (SD) and median (min_max). The normality of the numerical data was assessed using the Kolmogorov−Smirnov and Shapiro−Wilk tests, respectively, For numerical data that did not exhibit a normal distribution, the distribution between two independent groups was evaluated using the Mann−Whitney U test, and for more than two groups, the Kruskal−Walli’s test was employed. In groups for which the results of the Kruskal−Walli’s test were significant, the Mann−Whitney U test was used for post hoc analysis, accompanied by Dunn's Bonferroni correction. The relationships between two nonnormally distributed numerical variables were examined using Spearman’s correlation analysis. Correlation relationships were classified as follows: r = 0.05–0.30 indicated a weak correlation, r = 0.30–0.40 indicated a weak to moderate correlation, r = 0.40–0.60 indicated a moderate correlation, r = 0.60–0.70 indicated a good correlation, r = 0.70–0.75 indicated a very good correlation, and r = 0.75-1.00 indicated an excellent correlation. The cutoff point determination characteristics of the markers measured by OCT, EDI-OCT, and OCT-A for the presence of uveitis were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS A total of 119 individuals were included in the study and divided into three groups: 37 patients with posterior uveitis or panuveitis secondary to Behçet’s disease (BU) (Group 1), 42 patients with Behçet’s disease without ocular involvement (Group 2), and 40 age- and sex-matched healthy controls. In patients with BU, the eyes with more severe involvement were analyzed (25 right eyes and 12 left eyes). OCT, OCT angiography, and EDI-OCT measurements were obtained during the remission period, whereas fluorescein angiography (FA) data were retrospectively evaluated from images acquired during the initial attack. The mean age was 37.35 ± 10.62 years in the BU group, 36.21 ± 7.08 years in the nonocular BD group, and 33.50 ± 9.84 years in the control group, with no significant differences in age or sex distribution among the groups (p = 0.129). The demographic and clinical characteristics are summarized in Table II. Table III shows a comparison of the imaging results obtained from all participants using OCT, OCT-A, and EDI-OCT. Compared with that in the other two groups, the central macular thickness in the BU group was significantly lower (p=0.025). No significant difference in RNFL thickness was detected (p=0.262). The FAZ area in the BU group was 290.21 ±60.01 µm² on average, whereas in the BD group without uveitis and the control group, the values were 250.02 ±40.02 µm² and 230.02 ±50.07 µm², respectively (p=0.001). Significant differences were detected among the groups when the capillary plexus density ratios in all areas included in the study were compared (superficial, deep, parafoveal–superficial, parafoveal–deep, and radial peripapillary areas) (p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively). The central subfoveal choroidal thickness obtained via EDI-OCT was 266.27±28.64 µm in Group 1, which was significantly greater than that in Group 2 (219.28±20.25 µm) and that in Group 2 (219.65±15.51 µm) (p<0.001). Table IV presents the relationships between treatment modalities and imaging parameters in BU patients. No statistically significant differences were observed in age, disease duration, number of relapses, or interval between fluorescein angiography and other imaging (p > 0.05). Similarly, the OCT, OCTA, and EDI-OCT parameters did not differ significantly differ among the treatment groups. (p > 0.05). In contrast, FA scores significantly differed among the treatment groups (p < 0.05), with higher scores observed in patients receiving anti-TNF therapy Table V presents a comparison of the OCT, OCT-A, and EDI-OCT parameters between the BD group without uveitis and the control group. The central macular thickness (CMT), retinal nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, and choroidal vascular density (CVD) (both deep and parafoveal deep) were significantly similar between the BD without uveitis group and the control group (p=0.099; p=0.213; p=0.079; p=0.055; p=0.346; p=0.831, respectively). However, CVD in the superficial, parafoveal–superficial, and radial peripapillary regions was significantly lower in the BD without uveitis group than in the control group (p=0.008; p=0.014; p<0.001, respectively). The associations between OCT, OCTA, and EDI-OCT parameters, as well as FA scores, disease duration, number of relapses, visual acuity, and the interval between remission and activation in patients with BU, are presented in Table VI. No statistically significant correlations were found between disease duration, number of relapses, or the interval between remission and activation and OCT, OCTA, or EDI-OCT parameters or between disease duration and FA score (p > 0.05). A moderate negative correlation was observed between visual acuity (VA) and RNFL central thickness, as well as between VA and CVD (radial peripapillary). (r = -0.406, p = 0.013; r = -0.538, p = 0.001, respectively). The correlations between the FA scores obtained from the BU group and the OCT, OCT-A, and EDI-OCT parameters are shown in Table VII. A moderate positive relationship was observed between the FA score and the FAZ area (r=0.449, p<0.001). A negative relationship was observed between the FA score and capillary-to-vascular ratio in both the deep and superficial areas. ROC analysis was performed to evaluate the diagnostic performance of OCT, EDI-OCT, and OCT-A parameters in predicting uveitis in patients (Table VIII). ROC analysis revealed that the radial peripapillary capillary vessel density (CVD) demonstrated diagnostic performance in predicting uveitis activity in patients with Behçet’s uveitis (AUC = 0.992), with a sensitivity and specificity of 97.3% and 95.2%, respectively (Figure 3). ChT also showed high diagnostic accuracy (AUC = 0.895), with a cutoff value of ≥238 µm yielding a sensitivity of 89.5% and a specificity of 86.4%. In contrast, the FAZ area (AUC = 0.669) and superficial and deep CVD parameters (AUC range: 0.676–0.725) exhibited only moderate discriminative ability (Figure 4). DISCUSSION FA is the gold standard for identifying signs of inflammation in the posterior segment, including the retina periphery. It may be used to detect the foveal avascular zone immediately after intravenous dye injection; however, it is invasive in nature and does not allow the involvement of the superficial and deep capillary vascular layers to be separated ( 14 , 17 , 18 ). OCT-A, which has been used for the past decade in patients with uveitis and other inflammatory disorders involving the posterior pole, is a noninvasive method that does not require fluorescent dye and allows three-dimensional visualization of changes in the microvasculature of the superficial and deep retina. The availability of OCT-A has contributed to the implementation of numerous studies evaluating microvascular structures in follow-up patients with BU ( 10 – 13 ). The primary objective of this study was to evaluate the long-term impact of BU on the retinal and choroidal microvasculature during clinical remission. While conventional clinical examinations often suggest a return to normal clinical findings after an acute attack, our findings along with those many other studies using OCT-A and EDI-OCT reveal that significant structural and vascular alterations persist even in the inactive phase ( 11 – 14 , 17 ). The current study demonstrated that BU leaves a permanent and measurable inflammatory imprint on the retinal microvasculature, which persists even during periods of clinical remission. While patients with BU exhibited a generalized decrease in capillary vessel density (CVD) across both superficial and deep capillary plexuses (SCP and DCP) compared with healthy controls, our findings highlight several critical nuances regarding how this damage occurs and where it is most detectable. A significant finding of our study was that the peripapillary region may be more sensitive than the macular region in detecting early vascular changes. Notably, we found that even patients with BD without ocular involvement had significantly lower CVD in the peripapillary area, whereas their macular parameters remained relatively preserved. This finding supports the observation by Yan et al. that vascular changes in BU are more prominent in the peripapillary zone ( 18 ). The fact that peripapillary changes were detectable in the nonocular Behçet’s disease group suggests that this area could serve as a sensitive biomarker for identifying subclinical ocular involvement. A major point of discussion in the literature is whether microvascular damage is related to the frequency of relapses. Accorinti et al. and Cheng et al. reported an inverse association between vessel density and the number of ocular attacks and reported that damage increases with increasing recurrence ( 14 , 19 ). In contrast, our study revealed no significant correlation between relapse frequency and OCT or OCTA parameters. This discrepancy suggests that permanent microvascular damage in BU may be driven more by the severity of the initial inflammatory insult than by the cumulative number of attacks. We identified a significant relationship between baseline FA scores, which represent the intensity of vascular leakage and inflammation, and CVD parameters in remission. Specifically, the moderate positive correlation (r = 0.449) between the FA score and the foveal avascular zone (FAZ) area suggests that the intensity of the initial vasculitic phase reflects the extent of irreversible capillary nonperfusion. This finding aligns with the findings of Eser-Ozturk et al., who also reported that capillary vessel density in multiple regions correlated with FA scores ( 12 ). Our results confirm that the DCP is more severely affected than the superficial layers are in patients with BU. This finding is consistent with a consensus in the literature; Accorinti et al., Khairallah et al., Aksoy et al., Emre et al., and Somkijrungroj et al, reported that BU causes more significant damage to and disorganization of deeper capillary layers ( 10 , 11 , 14 , 20 , 21 ). Owing to its anatomy, the DCP appears to be more susceptible to the ischemic insults and inflammatory imprinting described in our study. Our results bridge the gap between clinical examination and structural damage by showing that a quiet clinical examination does not necessarily equate to microvascular recovery. We propose that initial angiographic severity, quantified by FA scoring, is a more accurate indicator of long-term structural outcomes than the frequency of relapses alone. These findings emphasize the importance of early and aggressive management of the first inflammatory episode to minimize the permanent inflammatory damage to the retina. We observed a significant reduction in central macular thickness in BU eyes (p = 0.025), which likely reflects chronic tissue loss following inflammation and subsequent ischemia. A study revealed that foveal thickness reduction in BU due to foveal intraretinal cystoid changes leads to permanent structural damage ( 22 ). Similarly, Cheng et al. reported comparable findings in their investigation of the correlation between the inner and outer retinal layers of the macula and visual activity ( 19 ). When OCT images were used, Unoki et al. reported that cases with ellipsoid zones demonstrated greater foveal thickness loss ( 22 ). The experiments of Oray et al. reported that infiltrates of the retina observed during the active phase of inflammation recover without scarring but create a local defect in the RNFL ( 23 ). Kido et al. reported that uveitis involvement leads to outer plexiform layer elevation, ultimately leading to a reduction visual acuity ( 24 ). Owing to its simplicity and ease of application, OCT is a helpful modality for patient follow-up. EDI-OCT is important for visualizing the posterior choroid and plays a crucial role in the diagnosis and monitoring of chorioretinal diseases. Atmaca et al. reported hyperfluorescence and/or hypofluorescence in ICGA, irregular filling of the choriocapillaris, choroidal filling defects, and ICG leakage from choroidal vessels, suggesting the presence of choroidal involvement in BU ( 25 ). According to studies by Yesilirmak et al. and Coskun et al., choroidal thickness decreases with time patients with in chronic or end-stage BD because of fibrosis, ischemia, and tissue atrophy, but it is greatest during acute stages because of inflammation and vascular alterations ( 26 , 27 ). Kim et al. reported that choroidal thickness was greater in both the active and remission phases than in healthy controls did, indicating persistent subclinical inflammation, despite the finding of no significant difference in choroidal thickness between BD patients with and without ocular involvement by Karadag et al. ( 28 , 29 ). In our study, subfoveal choroidal thickness (ChT) remained significantly greater in the BU group (266.27 ± 28.64 µm) than in nonocular BD (219.28 ± 20.25 µm) and control (219.65 ± 15.51 µm) groups. This persistent thickening during remission is a noteworthy paradox, while retinal layers thin because of atrophy, the choroid appears to remain thickened, possibly because of permanent vascular remodeling or subclinical, low-grade chronic inflammation. These findings support the use of EDI-OCT as a sensitive tool for detecting ongoing subclinical ocular involvement. In our retrospective analysis, we utilized a modified semiquantitative analysis based on the ASUWOG scoring system to evaluate fluorescein angiography (FA) images taken during active attacks. This refined method allows for a detailed calculation of FA data, bridging the gap between clinical observation and measurable vascular damage. The validity of this scoring system is wellsupported in the literature; for instance, Kabaalioglu Guner et al. and Tugal-Tutkun et al. reported high correlations between this specific FA scoring system and laser flare-cell photometry values ( 16 , 30 ). These correlations confirm that the FA scores reflect the level of intraocular inflammation and blood-aqueous barrier breakdown. Therefore, the significant relationship we found between high baseline FA scores and reduced CVD in remission is grounded in a reliable and scientifically validated assessment of inflammatory severity. Despite its clinical implications, our study has several limitations. First, its retrospective nature limits the ability to control for all the variables during the follow-up period. Second, while our sample size (n = 119) is substantial for this disease, larger prospective studies are needed to validate the strength of the ability of FA scores to predict long-term visual prognosis. Finally, the potential influence of different systemic immunosuppressive treatments on microvascular measurements was not fully analyzed and remains a subject for future research. In conclusion, our study demonstrates that Behçet’s disease causes a permanent damage to the retinal microvasculature that persists even during clinical remission. We found that compared with macular parameters, peripapillary vessel density is a more sensitive biomarker for subclinical involvement, with significant changes observed even in Behçet disease patients without a history of uveitis Furthermore, our results suggest that the severity of the initial inflammatory insult, rather than the total number of relapses, is the primary driver of long-term structural damage. These findings emphasize the critical importance of early and aggressive treatment from the very first attack to minimize irreversible vascular loss and preserve visual function. Declarations CORRESPONDING AUTHOR Şerife Nur Çiftci, Assistant Professor of Ophthalmology, Uşak University, Uşak, Türkiye Email: [email protected] / Phone: +90 554 807 60 28 FUNDING STATEMENT This study did not receive any funding. ETHICS APPROVAL AND CONSENT TO PARTICIPATE The study protocol was approved by the Ethics Committee of Necmettin Erbakan University (Approval No.2022/3687) and adhered to the principles of the Declaration of Helsinki. Owing to the retrospective design of the study, the requirement for informed consent was waived. ACKNOWLEDGMENTS The authors would like to thank Mithat Çopur for his technical support and all the participants who contributed to this study. DECLARATION OF INTEREST The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study. Author Contribution ŞNÇ and GŞ equally contributed to the design and implementation of the research; ŞNÇ, GŞ, AK and MO contributed to data collection and analysis of the results. Literature review, editing, and supervision were conducted by GŞ, and all authors contributed to the final manuscript writing. 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Fluorescein and indocyanine green angiography findings in Behçet's disease. Br J Ophthalmol. 2003;87(12):1466–8. Yesilirmak N, Lee WH, Gur Gungor S, et al. Enhanced depth imaging optical coherence tomography in patients with different phases of Behcet’s panuveitis. Can J Ophthalmol 2017;52:48–53. Coskun E, Gurler B, Pehlivan Y, et al. Enhanced depth imag- ing optical coherence tomography findings in Behçet disease. Ocul Immunol Inflamm 2013;21:440–445. Kim M, Kim H, Kwon HJ, et al. Choroidal thickness in Beh- cet’s uveitis: an enhanced depth imaging-optical coherence tomography and its association with angiographic changes. Invest Ophthalmol Vis Sci 2013;54:6033–6039. Karadag AS, Bilgin B, Soylu MB. Comparison of optical coherence tomographic findings between Behcet disease patients with and without ocular involvement and healthy sub- jects. Arq Bras Oftalmol. 2017;80:69–73. Tugal-Tutkun I, Cingü K, Kir N, Yeniad B, Urgancioglu M, Gül A. Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Beḩçet uveitis. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2008;246(8):1169–77. Tables Tables 1 to 8 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 22 May, 2026 Reviewers agreed at journal 22 May, 2026 Reviewers agreed at journal 20 May, 2026 Reviewers agreed at journal 20 May, 2026 Reviewers invited by journal 06 May, 2026 Editor assigned by journal 02 May, 2026 Submission checks completed at journal 02 May, 2026 First submitted to journal 30 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9581546","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":638015687,"identity":"745cccfb-d3db-4a0c-9135-813b34963f56","order_by":0,"name":"Şerife Nur Çiftci","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYDACZsYHDAwGMAYDgxyIOPAArxZmwwaIFmYQyWAM1pKA3xqgFggDrCURzMOnhb+dmf3Bj4I6OfN2ZsbHhW330ueHHX4ItMVOTrcBuxaJw8yMjT0Gh41lDjMzG89sK87deDvNAKgl2djsAHYtBsz8B5sZDA4kzmDmPybN25aQu3F2AkjLgcRtOLUwMwK11NXPYGZm/w3Ukm44O/0DMVqYEySYmdmYgVoS5KVz8NsC8stMoF8MgbYwS/OcSzDcIJ1TcCDBALdf+PsPM3z48adOXoL/MONnnrIEefnZ6Zs/fKiwk8OlBYtTwSoNiFUOAvINpKgeBaNgFIyCkQAAxzlVoSzopQsAAAAASUVORK5CYII=","orcid":"","institution":"Usak University","correspondingAuthor":true,"prefix":"","firstName":"Şerife","middleName":"Nur","lastName":"Çiftci","suffix":""},{"id":638015688,"identity":"2e1d49dc-874f-4496-a9e7-99a33cf35616","order_by":1,"name":"Günhal ŞATIRTAV","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Günhal","middleName":"","lastName":"ŞATIRTAV","suffix":""},{"id":638015690,"identity":"59cf8297-c853-49dc-87db-aae72e4c4bfe","order_by":2,"name":"Adem Küçük","email":"","orcid":"","institution":"Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Adem","middleName":"","lastName":"Küçük","suffix":""},{"id":638015692,"identity":"9de6febc-9599-4237-aced-45ee198a88a8","order_by":3,"name":"Mustafa Oğul","email":"","orcid":"","institution":"Pazarcık State Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"","lastName":"Oğul","suffix":""}],"badges":[],"createdAt":"2026-04-30 22:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9581546/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9581546/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109435049,"identity":"d9b14a88-f7b7-44d1-920b-15dff0d8b807","added_by":"auto","created_at":"2026-05-18 05:56:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1061226,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea.\u003c/strong\u003e ETDRS rings on angio-macula in the superficial layer (fovea, parafovea, and perifovea). \u003cstrong\u003eb.\u003c/strong\u003eDeep layer, \u003cstrong\u003ec.\u003c/strong\u003e FAZ was automatically measured. \u003cstrong\u003ed.\u003c/strong\u003e Angio-optic nerve head (total, insidedisc, peripapillary) with a 4.5 × 4.5 mm scan size\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/019fb294acec5e8684cfba02.png"},{"id":109435048,"identity":"f993aeef-73a3-4f13-9bfa-6c5b52662f0c","added_by":"auto","created_at":"2026-05-18 05:56:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":340091,"visible":true,"origin":"","legend":"\u003cp\u003ePanoramic figure created from fluorescein angiography late-phase images of the left eye of a Behçet uveitis patient taken during the active phase. Optic disc hyperfluorescence and leakage in all quadrants and the posterior pole were observed.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/d9d0644318fd5d6d63a22425.png"},{"id":109435047,"identity":"e39ba9e0-28ea-4f4f-a94f-d104ec6c01b1","added_by":"auto","created_at":"2026-05-18 05:56:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37973,"visible":true,"origin":"","legend":"\u003cp\u003eROC Analysis of FAZ and ChT Parameters\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/addbe1b190104aded994c345.png"},{"id":109435046,"identity":"b859f3c8-2be0-4569-b6d9-59067593496c","added_by":"auto","created_at":"2026-05-18 05:56:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":46189,"visible":true,"origin":"","legend":"\u003cp\u003eROC analysis of CVD-superficial, CVD-parafoveal superficial, CVD-deep, CVD-parafoveal deep, and CVD radial peripapillary parameters\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/67435eeae98ef5a3aad7fdbe.png"},{"id":109760705,"identity":"79b13247-7c11-4018-beda-401afd3fc79d","added_by":"auto","created_at":"2026-05-22 07:29:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1675243,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/8793b667-331e-4ebe-8772-8fa536204ba3.pdf"},{"id":109435045,"identity":"bd0f5e0a-c705-4c9d-8a36-509c881b1b4d","added_by":"auto","created_at":"2026-05-18 05:56:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":462517,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-9581546/v1/a5ac77688608da44d02a4de2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multimodal OCT and OCT-Angiography Findings in Behçet Disease: Evidence of Persistent Microvascular Alterations and Association with Fluorescein Angiography","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBehcet\u0026rsquo;s disease (BD) is a chronic, relapsing, multisystemic disorder characterized by inflammatory systemic occlusive vasculitis (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). It is a worldwide disease but is more frequent in Mediterranean countries and Japan (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). BD accounts for approximately 24.9% of noninfectious uveitis cases in the Turkish population, and serves the primary etiology (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOcular involvement occurs in approximately 50\u0026ndash;70% of patients with BD (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This usually manifests as multiple episodes of nongranulomatous, necrotizing inflammation in the posterior segment, which are explosive in nature and responsive to steroids. Anterior uveitis can present as nongranulomatous in nature, affecting up to 80% of cases, with several cases being symptomatic with transitory hypopyon (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Patients may also experience conjunctivitis, episcleritis, and keratitis. However, posterior uveitis is vastly detrimental to vision as a result of recurrent vascular occlusions, retinal hemorrhages and exudates, vascular sheathing, cystoid macular edema, retinal infiltrates, vitritis, and occasionally, optic neuropathy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFundus fluorescein angiography (FA) is the gold standard method for the diagnosis and follow-up of Behcet\u0026rsquo;s vasculitis. It is a crucial imaging method for determining the severity of inflammation and monitoring the treatment response in cases of posterior involvement (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Optical coherence tomography angiography (OCTA) is a noninvasive, repeatable, high-resolution imaging technique that provides information about foveal and peripapillary microvascular structures without the need for contrast agent injection. Careful interpretation of optic coherence tomography (OCT) and OCTA images can aid in follow-up, clinical outcome prediction, and differential diagnosis of uveitis(\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The first assessment of OCTA in active BU was performed by Khairallah in 48 eyes of 25 patients and revealed a significant effect on the deep retinal capillary plexus compared with the superficial retinal capillary plexus (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Numerous subsequent investigations have shown decreased vascular density in Beh\u0026ccedil;et uveitis patients during the active and inactive periods by comparing parafoveal and peripapillary microvascular alterations with those in healthy subjects (\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary objective of this study was to investigate whether the persistent retinal and choroidal microvascular alterations observed during clinical remission reflect the initial inflammatory burden documented at diagnosis and to evaluate the potential of these structural parameters as objective, noninvasive biomarkers of the cumulative ocular damage sustained in Beh\u0026ccedil;et Uveitis patients.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eThis retrospective study was conducted at the Department of Ophthalmology, Necmettin Erbakan University between February 2021 and February 2022. The study protocol was approved by the Ethics Committee of Necmettin Erbakan University (Approval No. 2022/3687) and adhered to the principles of the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eA total of 119 participants were included and divided into three groups: 37 patients with Beh\u0026ccedil;et uveitis (BU) presenting with posterior uveitis or panuveitis, 42 patients with Beh\u0026ccedil;et disease (BD) without ocular involvement, and 40 age- and sex-matched healthy controls. In the BU group, the more severely affected eye was included for analysis, whereas the right eye was analyzed in the nonocular BD and healthy groups. Healthy controls had no history of systemic disease, chronic ocular pathology, or ocular surgery, and had spherical and cylindrical refractive errors within the \u0026minus;\u0026thinsp;3.0 to +\u0026thinsp;3.0 diopter range.\u003c/p\u003e \u003cp\u003eAll participants underwent a comprehensive ophthalmological evaluation performed by a single experienced ophthalmologist. The evaluations included best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, intraocular pressure measurement, gonioscopy, and dilated fundus examination. BCVA values were then transformed to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis since it was originally taken with Snellen notation.\u003c/p\u003e \u003cp\u003eThe patients with BU were additionally evaluated according to the number of relapses, disease duration, t interval between the active phase (during which FA scores were obtained) and the remission phase (during which other parameters were measured), and treatment regimens used.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOCT and OCT angiography imaging\u003c/h3\u003e\n\u003cp\u003eSpectral-domain optical coherence tomography (SD-OCT), enhanced depth imaging OCT (EDI-OCT), and retinal nerve fiber layer (RNFL) thickness measurements were performed in all participants using a Heidelberg Spectralis OCT system (Heidelberg Engineering, Germany). Central macular thickness was measured within the central 1-mm diameter circle of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid.\u003c/p\u003e \u003cp\u003eOCT angiography (OCT-A) imaging was performed using the AngioVue OCT-A system (RTVue XR; Optovue Inc., Fremont, CA, USA) with software version 2018.1.0.37. The device software automatically segmented en face images of the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retinal layer, and choriocapillaris into four different layers. 6*6 mm macular and 4.5*4.5 mm optic disc OCTA images obtained with AngioVue technology were analyzed. Foveal (1.0-mm diameter) and parafoveal (1.0\u0026ndash;3.0 mm annulus) regions were analyzed according to the ETDRS grid. The foveal avascular zone (FAZ) area (\u0026micro;m\u0026sup2;) and peripapillary vessel density within a 750-\u0026micro;m annulus were automatically calculated using the software (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). OCTA images use the inner limiting membrane, outer border of the inner plexiform layer, outer border of the outer plexiform layer, and Bruch's membrane as landmarks. The automated layer segmentation provided by the device software was carefully inspected in each scan by two experienced graders, and scans with segmentation errors were excluded from the analysis. Images with significant projection or motion artifacts were excluded following a manual review. Only images with a signal strength and quality of at least 7/10 were included.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eFluorescein Angiography Assessment\u003c/h3\u003e\n\u003cp\u003eIn patients with BU, fluorescein angiography (FA) images obtained at the time of initial diagnosis were retrospectively reviewed. FA was performed using the Heidelberg HRA Spectralis system (Heidelberg Engineering, Germany) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Early- and late-phase (5\u0026ndash;8 min) images of the posterior pole and peripheral quadrants were evaluated and scored according to the Angiography Scoring for Uveitis Working Group (ASUWOG) system (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe proposed scoring system for reference during the FA and the total maximum score for each of the angiographic signs are given in Table I. Optic disc hyperfluorescence is scored from 1 to 3; target-like staining of the disc ,s given a score of 1, while leakage at the disc with blurring of the disc margins is given a score of 3. Neovascularization of the disc (NVD) receives an additional score of 2, whether it arises as a sequela of extensive retinal ischemia or severe intraocular inflammation does not matter. Macular edema was graded from 1 to 4, with pooling of dye in the cystic spaces at the macula receiving a score of 4. The staining or leakage of retinal vessel walls may be focal/multifocal or diffuse along the course of the vessels. This scoring was performed for the posterior pole arcades. For other parts of the retinal vascular tree, involvement was scored as absent or present, with 1 for each quadrant exhibiting the finding to any degree. However capillary leakage is considered a more specific indicator of inflammation, and we chose to score this finding to reflect the importance of this variable instead of simply documenting its presence or absence. Retinal capillary nonperfusion is graded according to the number of quadrants involved and is not considered a direct measure of inflammation; any area of capillary nonperfusion situated in the posterior pole is given in an additional score of 1, irrespective of whether there is advanced enlargement of the central avascular zone. Pinpoint leakage and subretinal pooling of the dye may be focal or extensive. The maximum total score for FA is 40 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The FAs were scored by two masked interpreters, and in cases of disagreement, the final score was obtained through discussion.\u003c/p\u003e \u003cp\u003eMacular, peripapillary, and choroidal parameters obtained using OCT, OCT-A, and EDI-OCT were quantitatively compared among patients with Beh\u0026ccedil;et\u0026rsquo;s uveitis, patients with Beh\u0026ccedil;et\u0026rsquo;s disease without ocular involvement, and healthy controls. In addition, in the Beh\u0026ccedil;et\u0026rsquo;s uveitis group, these parameters were analyzed in relation to fluorescein angiography scores obtained at the time of diagnosis.\u003c/p\u003e \u003cp\u003eThe data were analyzed using the Statistical Package for Social Sciences (SPSS) version 25.0 software. In the descriptive analyses, the frequency data were are presented as counts (n) and percentages (%), whereas the numerical data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and median (min_max). The normality of the numerical data was assessed using the Kolmogorov\u0026minus;Smirnov and Shapiro\u0026minus;Wilk tests, respectively, For numerical data that did not exhibit a normal distribution, the distribution between two independent groups was evaluated using the Mann\u0026minus;Whitney U test, and for more than two groups, the Kruskal\u0026minus;Walli\u0026rsquo;s test was employed. In groups for which the results of the Kruskal\u0026minus;Walli\u0026rsquo;s test were significant, the Mann\u0026minus;Whitney U test was used for post hoc analysis, accompanied by Dunn's Bonferroni correction. The relationships between two nonnormally distributed numerical variables were examined using Spearman\u0026rsquo;s correlation analysis. Correlation relationships were classified as follows: r\u0026thinsp;=\u0026thinsp;0.05\u0026ndash;0.30 indicated a weak correlation, r\u0026thinsp;=\u0026thinsp;0.30\u0026ndash;0.40 indicated a weak to moderate correlation, r\u0026thinsp;=\u0026thinsp;0.40\u0026ndash;0.60 indicated a moderate correlation, r\u0026thinsp;=\u0026thinsp;0.60\u0026ndash;0.70 indicated a good correlation, r\u0026thinsp;=\u0026thinsp;0.70\u0026ndash;0.75 indicated a very good correlation, and r\u0026thinsp;=\u0026thinsp;0.75-1.00 indicated an excellent correlation. The cutoff point determination characteristics of the markers measured by OCT, EDI-OCT, and OCT-A for the presence of uveitis were evaluated using receiver operating characteristic (ROC) curve analysis.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 119 individuals were included in the study and divided into three groups: 37 patients with posterior uveitis or panuveitis secondary to Beh\u0026ccedil;et\u0026rsquo;s disease (BU) (Group 1), 42 patients with Beh\u0026ccedil;et\u0026rsquo;s disease without ocular involvement (Group 2), and 40 age- and sex-matched healthy controls. In patients with BU, the eyes with more severe involvement were analyzed (25 right eyes and 12 left eyes). OCT, OCT angiography, and EDI-OCT measurements were obtained during the remission period, whereas fluorescein angiography (FA) data were retrospectively evaluated from images acquired during the initial attack.\u003c/p\u003e\n\u003cp\u003eThe mean age was 37.35 \u0026plusmn; 10.62 years in the BU group, 36.21 \u0026plusmn; 7.08 years in the nonocular BD group, and 33.50 \u0026plusmn; 9.84 years in the control group, with no significant differences in age or sex distribution among the groups (p = 0.129). The demographic and clinical characteristics are summarized in Table II.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable III shows a comparison of the imaging results obtained from all participants using OCT, OCT-A, and EDI-OCT. Compared with that in the other two groups, the central macular thickness in the BU group was significantly lower (p=0.025). No significant difference in RNFL thickness was detected (p=0.262). The FAZ area in the BU group was 290.21 \u0026plusmn;60.01 \u0026micro;m\u0026sup2; on average, whereas in the BD group without uveitis and the control group, the values were 250.02 \u0026plusmn;40.02 \u0026micro;m\u0026sup2; and 230.02 \u0026plusmn;50.07 \u0026micro;m\u0026sup2;, respectively (p=0.001). Significant differences were detected among the groups when the capillary plexus density ratios in all areas included in the study were compared (superficial, deep, parafoveal\u0026ndash;superficial, parafoveal\u0026ndash;deep, and radial peripapillary areas) (p\u0026lt;0.001, p\u0026lt;0.001, p\u0026lt;0.001, p\u0026lt;0.001, and p\u0026lt;0.001, respectively). The central subfoveal choroidal thickness obtained via EDI-OCT was 266.27\u0026plusmn;28.64 \u0026micro;m in Group 1, which was significantly greater than that in Group 2 (219.28\u0026plusmn;20.25 \u0026micro;m) and that in Group 2 (219.65\u0026plusmn;15.51 \u0026micro;m) (p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eTable IV presents the relationships between treatment modalities and imaging parameters in BU patients. No statistically significant differences were observed in age, disease duration, number of relapses, or interval between fluorescein angiography and other imaging (p \u0026gt; 0.05). Similarly, the OCT, OCTA, and EDI-OCT parameters did not differ significantly differ among the treatment groups. (p \u0026gt; 0.05). In contrast, FA scores significantly differed among the treatment groups (p \u0026lt; 0.05), with higher scores observed in patients receiving anti-TNF therapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable V presents a comparison of the OCT, OCT-A, and EDI-OCT parameters between the BD group without uveitis and the control group. The central macular thickness (CMT), retinal nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, and choroidal vascular density (CVD) (both deep and parafoveal deep) were significantly similar between the BD without uveitis group and the control group (p=0.099; p=0.213; p=0.079; p=0.055; p=0.346; p=0.831, respectively). However, CVD in the superficial, parafoveal\u0026ndash;superficial, and radial peripapillary regions was significantly lower in the BD without uveitis group than in the control group (p=0.008; p=0.014; p\u0026lt;0.001, respectively).\u003c/p\u003e\n\u003cp\u003eThe associations between OCT, OCTA, and EDI-OCT parameters, as well as FA scores, disease duration, number of relapses, visual acuity, and the interval between remission and activation in patients with BU, are presented in Table VI. No statistically significant correlations were found between disease duration, number of relapses, or the interval between remission and activation and OCT, OCTA, or EDI-OCT parameters or between disease duration and FA score (p \u0026gt; 0.05). A moderate negative correlation was observed between visual acuity (VA) and RNFL central thickness, as well as between VA and CVD (radial peripapillary). (r = -0.406, p = 0.013; r = -0.538, p = 0.001, respectively).\u003c/p\u003e\n\u003cp\u003eThe correlations between the FA scores obtained from the BU group and the OCT, OCT-A, and EDI-OCT parameters are shown in Table VII. A moderate positive relationship was observed between the FA score and the FAZ area (r=0.449, p\u0026lt;0.001). A negative relationship was observed between the FA score and capillary-to-vascular ratio in both the deep and superficial areas.\u003c/p\u003e\n\u003cp\u003eROC analysis was performed to evaluate the diagnostic performance of OCT, EDI-OCT, and OCT-A parameters in predicting uveitis in patients (Table VIII). ROC analysis revealed that the radial peripapillary capillary vessel density (CVD) demonstrated diagnostic performance in predicting uveitis activity in patients with Beh\u0026ccedil;et\u0026rsquo;s uveitis (AUC = 0.992), with a sensitivity and specificity of 97.3% and 95.2%, respectively (Figure 3). ChT also showed high diagnostic accuracy (AUC = 0.895), with a cutoff value of \u0026ge;238 \u0026micro;m yielding a sensitivity of 89.5% and a specificity of 86.4%. In contrast, the FAZ area (AUC = 0.669) and superficial and deep CVD parameters (AUC range: 0.676\u0026ndash;0.725) exhibited only moderate discriminative ability (Figure 4).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eFA is the gold standard for identifying signs of inflammation in the posterior segment, including the retina periphery. It may be used to detect the foveal avascular zone immediately after intravenous dye injection; however, it is invasive in nature and does not allow the involvement of the superficial and deep capillary vascular layers to be separated (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOCT-A, which has been used for the past decade in patients with uveitis and other inflammatory disorders involving the posterior pole, is a noninvasive method that does not require fluorescent dye and allows three-dimensional visualization of changes in the microvasculature of the superficial and deep retina. The availability of OCT-A has contributed to the implementation of numerous studies evaluating microvascular structures in follow-up patients with BU (\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary objective of this study was to evaluate the long-term impact of BU on the retinal and choroidal microvasculature during clinical remission. While conventional clinical examinations often suggest a return to normal clinical findings after an acute attack, our findings along with those many other studies using OCT-A and EDI-OCT reveal that significant structural and vascular alterations persist even in the inactive phase (\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe current study demonstrated that BU leaves a permanent and measurable inflammatory imprint on the retinal microvasculature, which persists even during periods of clinical remission. While patients with BU exhibited a generalized decrease in capillary vessel density (CVD) across both superficial and deep capillary plexuses (SCP and DCP) compared with healthy controls, our findings highlight several critical nuances regarding how this damage occurs and where it is most detectable. A significant finding of our study was that the peripapillary region may be more sensitive than the macular region in detecting early vascular changes. Notably, we found that even patients with BD without ocular involvement had significantly lower CVD in the peripapillary area, whereas their macular parameters remained relatively preserved. This finding supports the observation by Yan et al. that vascular changes in BU are more prominent in the peripapillary zone (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The fact that peripapillary changes were detectable in the nonocular Beh\u0026ccedil;et\u0026rsquo;s disease group suggests that this area could serve as a sensitive biomarker for identifying subclinical ocular involvement.\u003c/p\u003e \u003cp\u003eA major point of discussion in the literature is whether microvascular damage is related to the frequency of relapses. Accorinti et al. and Cheng et al. reported an inverse association between vessel density and the number of ocular attacks and reported that damage increases with increasing recurrence (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In contrast, our study revealed no significant correlation between relapse frequency and OCT or OCTA parameters. This discrepancy suggests that permanent microvascular damage in BU may be driven more by the severity of the initial inflammatory insult than by the cumulative number of attacks. We identified a significant relationship between baseline FA scores, which represent the intensity of vascular leakage and inflammation, and CVD parameters in remission. Specifically, the moderate positive correlation (r\u0026thinsp;=\u0026thinsp;0.449) between the FA score and the foveal avascular zone (FAZ) area suggests that the intensity of the initial vasculitic phase reflects the extent of irreversible capillary nonperfusion. This finding aligns with the findings of Eser-Ozturk et al., who also reported that capillary vessel density in multiple regions correlated with FA scores (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur results confirm that the DCP is more severely affected than the superficial layers are in patients with BU. This finding is consistent with a consensus in the literature; Accorinti et al., Khairallah et al., Aksoy et al., Emre et al., and Somkijrungroj et al, reported that BU causes more significant damage to and disorganization of deeper capillary layers (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Owing to its anatomy, the DCP appears to be more susceptible to the ischemic insults and inflammatory imprinting described in our study.\u003c/p\u003e \u003cp\u003eOur results bridge the gap between clinical examination and structural damage by showing that a quiet clinical examination does not necessarily equate to microvascular recovery. We propose that initial angiographic severity, quantified by FA scoring, is a more accurate indicator of long-term structural outcomes than the frequency of relapses alone. These findings emphasize the importance of early and aggressive management of the first inflammatory episode to minimize the permanent inflammatory damage to the retina.\u003c/p\u003e \u003cp\u003eWe observed a significant reduction in central macular thickness in BU eyes (p\u0026thinsp;=\u0026thinsp;0.025), which likely reflects chronic tissue loss following inflammation and subsequent ischemia. A study revealed that foveal thickness reduction in BU due to foveal intraretinal cystoid changes leads to permanent structural damage (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Similarly, Cheng et al. reported comparable findings in their investigation of the correlation between the inner and outer retinal layers of the macula and visual activity (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). When OCT images were used, Unoki et al. reported that cases with ellipsoid zones demonstrated greater foveal thickness loss (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The experiments of Oray et al. reported that infiltrates of the retina observed during the active phase of inflammation recover without scarring but create a local defect in the RNFL (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Kido et al. reported that uveitis involvement leads to outer plexiform layer elevation, ultimately leading to a reduction visual acuity (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Owing to its simplicity and ease of application, OCT is a helpful modality for patient follow-up.\u003c/p\u003e \u003cp\u003eEDI-OCT is important for visualizing the posterior choroid and plays a crucial role in the diagnosis and monitoring of chorioretinal diseases. Atmaca et al. reported hyperfluorescence and/or hypofluorescence in ICGA, irregular filling of the choriocapillaris, choroidal filling defects, and ICG leakage from choroidal vessels, suggesting the presence of choroidal involvement in BU (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). According to studies by Yesilirmak et al. and Coskun et al., choroidal thickness decreases with time patients with in chronic or end-stage BD because of fibrosis, ischemia, and tissue atrophy, but it is greatest during acute stages because of inflammation and vascular alterations (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Kim et al. reported that choroidal thickness was greater in both the active and remission phases than in healthy controls did, indicating persistent subclinical inflammation, despite the finding of no significant difference in choroidal thickness between BD patients with and without ocular involvement by Karadag et al. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). In our study, subfoveal choroidal thickness (ChT) remained significantly greater in the BU group (266.27\u0026thinsp;\u0026plusmn;\u0026thinsp;28.64 \u0026micro;m) than in nonocular BD (219.28\u0026thinsp;\u0026plusmn;\u0026thinsp;20.25 \u0026micro;m) and control (219.65\u0026thinsp;\u0026plusmn;\u0026thinsp;15.51 \u0026micro;m) groups. This persistent thickening during remission is a noteworthy paradox, while retinal layers thin because of atrophy, the choroid appears to remain thickened, possibly because of permanent vascular remodeling or subclinical, low-grade chronic inflammation. These findings support the use of EDI-OCT as a sensitive tool for detecting ongoing subclinical ocular involvement.\u003c/p\u003e \u003cp\u003eIn our retrospective analysis, we utilized a modified semiquantitative analysis based on the ASUWOG scoring system to evaluate fluorescein angiography (FA) images taken during active attacks. This refined method allows for a detailed calculation of FA data, bridging the gap between clinical observation and measurable vascular damage. The validity of this scoring system is wellsupported in the literature; for instance, Kabaalioglu Guner et al. and Tugal-Tutkun et al. reported high correlations between this specific FA scoring system and laser flare-cell photometry values (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). These correlations confirm that the FA scores reflect the level of intraocular inflammation and blood-aqueous barrier breakdown. Therefore, the significant relationship we found between high baseline FA scores and reduced CVD in remission is grounded in a reliable and scientifically validated assessment of inflammatory severity.\u003c/p\u003e \u003cp\u003eDespite its clinical implications, our study has several limitations. First, its retrospective nature limits the ability to control for all the variables during the follow-up period. Second, while our sample size (n\u0026thinsp;=\u0026thinsp;119) is substantial for this disease, larger prospective studies are needed to validate the strength of the ability of FA scores to predict long-term visual prognosis. Finally, the potential influence of different systemic immunosuppressive treatments on microvascular measurements was not fully analyzed and remains a subject for future research.\u003c/p\u003e \u003cp\u003eIn conclusion, our study demonstrates that Beh\u0026ccedil;et\u0026rsquo;s disease causes a permanent damage to the retinal microvasculature that persists even during clinical remission. We found that compared with macular parameters, peripapillary vessel density is a more sensitive biomarker for subclinical involvement, with significant changes observed even in Beh\u0026ccedil;et disease patients without a history of uveitis Furthermore, our results suggest that the severity of the initial inflammatory insult, rather than the total number of relapses, is the primary driver of long-term structural damage. These findings emphasize the critical importance of early and aggressive treatment from the very first attack to minimize irreversible vascular loss and preserve visual function.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCORRESPONDING AUTHOR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eŞerife Nur \u0026Ccedil;iftci, Assistant Professor of Ophthalmology, Uşak University, Uşak, T\u0026uuml;rkiye Email: [email protected] / Phone: +90 554 807 60 28\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Necmettin Erbakan University (Approval No.2022/3687) and adhered to the principles of the Declaration of Helsinki. Owing to the retrospective design of the study, the requirement for informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Mithat \u0026Ccedil;opur for his technical support and all the participants who contributed to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDECLARATION OF INTEREST\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eŞN\u0026Ccedil; and GŞ equally contributed to the design and implementation of the research; ŞN\u0026Ccedil;, GŞ, AK and MO contributed to data collection and analysis of the results. Literature review, editing, and supervision were conducted by GŞ, and all authors contributed to the final manuscript writing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStandardization of Uveitis Nomenclature (SUN) Working Group. Classification Criteria for Beh\u0026ccedil;et Disease Uveitis. Am J Ophthalmol. 2021;228:80\u0026ndash;88..\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ccedil;akar \u0026Ouml;zdal P. Beh\u0026ccedil;et's Uveitis: Current Diagnostic and Therapeutic Approach. Turk J Ophthalmol. 2020;50(3):169\u0026ndash;182\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhong Z, Su G, Yang P. Risk factors, clinical features and treatment of Beh\u0026ccedil;et's disease uveitis. Prog Retin Eye Res. 2023;97:101216.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKazokoglu H, Onal S, Tugal-Tutkun I, Mirza E, Akova Y, Ozyazgan Y, Soylu M, Batioglu F, Apaydin C. Demographic and clinical features of uveitis in tertiary centers in Turkey. Ophthalmic Epidemiol. 2008 Sep-Oct;15(5):285\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzyazgan Y, Ucar D, Hatemi G, et al. Ocular Involvement of Beh\u0026ccedil;et\u0026rsquo;s Syndrome: A Comprehensive Review. Clin Rev Allergy Immunol. 2015;49:298\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaur M, Yip K. The Current and Novel Imaging Modalities for Ocular Vasculitis in Behcet's Disease: A Review. Cureus. 2024;16(9):e69528.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInvernizzi A, Cozzi M, Staurenghi G. Optical coherence tomography and optical coherence tomography angiography in uveitis: A review. Clin Exp Ophthalmol. 2019;47(3):357\u0026ndash;371.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal A, Invernizzi A. 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Photodiagnosis Photodyn Ther 2020;29:101646.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEser\u0026ndash;Ozturk H, Ismayilova L, Yucel OE, Sullu Y. Quantitative measurements with optical coherence tomography angiography in Beh\u0026ccedil;et uveitis. Eur J Ophthalmol 2021;31:1047\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoca S, Onan D, Kalaycı D, Allı N. Comparison of optical coherence tomography angiography findings in patients with Beh\u0026ccedil;et\u0026rsquo;s disease and healthy controls. Ocul Immunol Inflamm 2020;28:806\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAccorinti M, Gilardi M, De Geronimo D, Iannetti L, Giannini D, Parravano M. Optical coherence tomography angiography findings in active and inactive ocular Beh\u0026ccedil;et disease. Ocul Immunol Inflamm 2020;28:589\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTugal-Tutkun I, Herbort CP, Khairallah M, Allegri P, Biziorek B, Bodaghi B, et al. Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010;30(5):539\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKabaalioglu Guner M, Guner ME, Oray M, Tugal-Tutkun I. Correlation between Widefield Fundus Fluorescein Angiography Leakage Score and Anterior Chamber Flare in Beh\u0026ccedil;et Uveitis. Ocul Immunol Inflamm. 2024;32(1):54\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAygun O, Kadayifcilar S, Karakaya J, Eldem B. Assessment Of Clinical Features And Prognosis In Beh\u0026ccedil;et Disease Patients With Ocular Manifestations: A Focus On Optical Coherence Tomography And Angiography. Retina. 2025;45(12):2371\u0026ndash;2382.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYan C, Li F, Hou M, Ye X, Su L, Hu Y, Luo J, Chi W. Vascular Abnormalities in Peripapillary and Macular Regions of Behcet's Uveitis Patients Evaluated by Optical Coherence Tomography Angiography. Front Med (Lausanne). 2021;8:727151.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng D, Wang Y, Huang S, Wu Q, Chen Q, Shen M, et al. Macular Inner Retinal Layer Thickening And Outer Retinal Layer Damage Correlate With Visual Acuity During Remission In Behcet\u0026rsquo;s Disease. Invest Ophthalmol Vis Sci. 2016;57(13):5470\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmre S, G\u0026uuml;ven-Yılmaz S, Ulusoy MO, Ateş H. Optical coherence tomography angiography findings in Behcet patients. Int Ophthalmol. 2019;39(10):2391\u0026ndash;2399.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSomkijrungroj T, Vongkulsiri S, Kongwattananon W, Chotcomwongse P, Luangpitakchumpol S, Jaisuekul K. Assessment of Vascular Change Using Swept-Source Optical Coherence Tomography Angiography: A New Theory Explains Central Visual Loss in Behcet's Disease. J Ophthalmol. 2017;2017:2180723.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnoki N, Nishijima K, Kita M, Hayashi R, Yoshimura N. Structural changes of fovea during remission of Beh\u0026ccedil;et\u0026rsquo;s disease as imaged by spectral domain optical coherence tomography. Eye. 2010;24(6):969\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOray M, Onal S, Bayraktar S, Izgi B, Tugal-Tutkun I. Nonglaucomatous localized retinal nerve fiber layer defects in Beh\u0026ccedil;et uveitis. Am J Ophthalmol. 2015;159(3):475\u0026ndash;481.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKido A, Uji S, Morooka S, Kuroda Y, Arichika S, Akagi T, et al. Outer plexiform layer elevations as a marker for prior ocular attacks in patients with Behcet\u0026rsquo;s disease. Invest Ophthalmol Vis Sci. 2018;59(7):2828\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAtmaca LS, Sonmez PA. Fluorescein and indocyanine green angiography findings in Beh\u0026ccedil;et's disease. Br J Ophthalmol. 2003;87(12):1466\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYesilirmak N, Lee WH, Gur Gungor S, et al. Enhanced depth imaging optical coherence tomography in patients with different phases of Behcet\u0026rsquo;s panuveitis. Can J Ophthalmol 2017;52:48\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoskun E, Gurler B, Pehlivan Y, et al. Enhanced depth imag- ing optical coherence tomography findings in Beh\u0026ccedil;et disease. Ocul Immunol Inflamm 2013;21:440\u0026ndash;445.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim M, Kim H, Kwon HJ, et al. Choroidal thickness in Beh- cet\u0026rsquo;s uveitis: an enhanced depth imaging-optical coherence tomography and its association with angiographic changes. Invest Ophthalmol Vis Sci 2013;54:6033\u0026ndash;6039.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaradag AS, Bilgin B, Soylu MB. Comparison of optical coherence tomographic findings between Behcet disease patients with and without ocular involvement and healthy sub- jects. Arq Bras Oftalmol. 2017;80:69\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTugal-Tutkun I, Cing\u0026uuml; K, Kir N, Yeniad B, Urgancioglu M, G\u0026uuml;l A. Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Beḩ\u0026ccedil;et uveitis. Graefe\u0026rsquo;s Archive for Clinical and Experimental Ophthalmology. 2008;246(8):1169\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 8 are available in the Supplementary Files section.\u003c/p\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":"Behçet Disease, Behçet Uveitis, Optical Coherence Tomography Angiography, Fundus Fluorescein Angiography","lastPublishedDoi":"10.21203/rs.3.rs-9581546/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9581546/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate macular, peripapillary, and choroidal microvascular alterations in patients with Behcet\u0026rsquo;s disease (BD) using optical coherence tomography (OCT), OCT angiography (OCT-A) and enhanced depth imaging (EDI-OCT), and to determine the relationship between these alterations and fluorescein angiography (FA) findings.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 119 participants: 37 patients with Beh\u0026ccedil;et uveitis (BU), 42 patients with nonocular BD and 40 healthy controls. OCT, OCT-A, and EDI-OCT were performed on all the participants. In the BU group, measurements were obtained during clinical remission and analyzed in relation to FA images acquired at the initial diagnosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe foveal avascular zone (FAZ) area was significantly larger in eyes with BU than in those with nonocular BD and healthy controls (p\u0026thinsp;=\u0026thinsp;0.001). Capillary vessel density (CVD) in both the superficial and deep capillary plexuses was significantly reduced in BU eyes (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for both). Subfoveal choroidal thickness (ChT) was significantly greater in the BU group than in the other groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). FA scores demonstrated a moderate positive correlation with the FAZ area (r\u0026thinsp;=\u0026thinsp;0.449, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a negative correlation with superficial and deep CVD parameters. Central macular thickness was significantly lower in the BU group (p\u0026thinsp;=\u0026thinsp;0.025).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOCT-A and EDI-OCT demonstrated persistent retinal and choroidal microvascular alterations in patients with BU, even during remission. These noninvasive parameters were significantly associated with baseline FA findings, indicating that the severity of the initial inflammatory insult may play a significant role in long-term structural damage. These observations highlight the potential importance of early and effective management of initial inflammatory episodes to minimize irreversible vascular loss.\u003c/p\u003e","manuscriptTitle":"Multimodal OCT and OCT-Angiography Findings in Behçet Disease: Evidence of Persistent Microvascular Alterations and Association with Fluorescein Angiography","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-18 05:56:02","doi":"10.21203/rs.3.rs-9581546/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-23T01:50:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90230887331378030629884416569499346808","date":"2026-05-23T01:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78621278576111944000917514320955995750","date":"2026-05-20T10:44:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"63120151389186607519870846100099604271","date":"2026-05-20T10:21:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-06T14:41:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-02T15:07:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-02T15:07:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2026-04-30T22:43:43+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":"3a5db852-a4e9-4e49-94d1-8327cc06f589","owner":[],"postedDate":"May 18th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-23T01:50:23+00:00","index":98,"fulltext":""},{"type":"reviewerAgreed","content":"90230887331378030629884416569499346808","date":"2026-05-23T01:34:47+00:00","index":97,"fulltext":""},{"type":"reviewerAgreed","content":"78621278576111944000917514320955995750","date":"2026-05-20T10:44:00+00:00","index":94,"fulltext":""},{"type":"reviewerAgreed","content":"63120151389186607519870846100099604271","date":"2026-05-20T10:21:16+00:00","index":93,"fulltext":""},{"type":"reviewersInvited","content":"77","date":"2026-05-06T14:41:50+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T05:56:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-18 05:56:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9581546","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9581546","identity":"rs-9581546","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}