Correlation between aqueous humour cytokine and Imaging Biomarker in CRVO-ME

Correlation between aqueous humour cytokine and Imaging Biomarker in CRVO-ME | 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 Correlation between aqueous humour cytokine and Imaging Biomarker in CRVO-ME Jie Gao, Huiwen Pang, Weijie Zhang, Maojuan Feng, Tao Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9449389/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Objective This study aims to examine the relationship between the concentrations of different aqueous humour cytokine and the Central retinal thickness (CRT), the area of the Foveal avascular zone (FAZ)and the vascular density of superficial capillary plexus (SCP-VD) in patients with Central Retinal Vein Occlusion-Macular Edema ༈CRVO-ME༉ through a prospective clinical investigation. Methods A total of 20 cases with 20 eyes were included from Linyi Peoples Hospital. OCT and OCTA were employed to examine a 6 mm × 6 mm region in the macula, acquiring CRT, FAZ area, and SCP-VD data. Aqueous humor samples were collected to measure its Interleukin-6(IL-6),Interleukin-8 ( IL-8),Vascular endothelial growth factor (VEGF༉, Vascular cell adhesion molecule (VCAM༉, Placental growth factor ( PGF༉, and Monocyte chemoattractant protein-1 (MCP-1༉ level. The correlation between these values of CRT, FAZ area, and SCP-VD in the affected eye were analyzed using statistical Pearson methods. Results The CRT of the affected eye in CRVO-ME patients was (572.80 ± 186.57) µm; the SCP-VD was (39.73 ± 1.56) %; and the FAZ area was (0.45 ± 0.06) mm². The concentrations of IL-6, IL-8, VEGF, VCAM, PGF, and MCP-1 in CRVO-ME patients were (151.16 ± 88.61), (38.63 ± 22.29), (107.72 ± 96.76), (2177.02 ± 2357.69), (76.53 ± 29.48), and (617.69 ± 205.87) pg/ml, respectively. Correlation analysis showed that CRT was significantly positively correlated with the IL-6 and VEGF concentrations (r = 0.450,0.593, P < 0.05); FAZ area was significantly positively correlated with VEGF (r = 0.489, P < 0.05); and SCP-VD was significantly negatively correlated with IL-6 (r = -0.462, P < 0.05). Conclusions The concentration of intraocular cytokines exhibited a substantial correlation with the macular structure of the macula and the extent of microvascular damage surrounding the macula. Macular edema Central retinal vein occlusion humour cytokine Biological markers Ophthalmology Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Macular edema (ME) is a significant contributor to vision impairment in individuals with Retinal Vein Occlusion (RVO) [1] . The prevailing belief is that the primary pathophysiology of the disease involves the disruption of Blood-Retinal Barrier (BRB), resulting in fluid accumulation in the macula, ultimately causing vision loss or even blindness [2] . According to recent identifications within fundus imaging and molecular biology, the pathophysiological processes of macular edema, and the control of aqueous humor cytokines (e.g., VEGF, IL-6) in particular has elevated interest. [3] .This study aims to investigate the relationship between biomarkers of fundus imaging and cytokine levels in Central retinal vein occlusive - macular edema (CRVO-ME), and to determine their possible usefulness in diagnosis, treatment and prognosis testing. In individuals with early CRVO, the buildup of metabolic byproducts within the arteries and the induction of an acidic milieu generate inflammatory mediators that result in leukocyte aggregation, hence producing microcirculatory disturbances in the retina [4] . This leads to non-perfused areas in the respective retinal regions, resulting in elevated VEGF levels as a compensatory response. Cytokines concurrently govern cell-to-cell interactions, influence inflammatory responses, engage in immunological responses, and facilitate tissue repair, hence supporting many physiological and pathological processes. In recent years, fundus imaging has been increasingly adopted in clinical practice. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) are the primary techniques for assessing the microstructure and pathological alterations of retinal layers and micro-vessels. Due to their non-invasive characteristics, optical coherence tomography has become a common method for detection and evaluation of ME in recent years [1, 4] .This non-contact, non-invasive optical imaging diagnostic method can reveal the cross-sectional architecture of the posterior segment of the eye, rendering it useful for examining subtle features such as subretinal fluid (SRF), intraretinal fluid (IRF), retinal inner layer structural disorder (DRIL), and high reflectance foci (HRF). In practical practice, physicians predominantly utilize OCT to perform qualitative and quantitative assessments of the several tissue layers in the macula to diagnose ME lesions. As a vascular imaging technology developed from OCT, OCTA can obtain the morphology and perfusion status of retinal blood, and their blood flow data in real time without invasiveness [5] .OCTA can accomplish stratified imaging of retinal and choroidal vessels while quantitatively assessing vascular density and lesion volume. OCT can provide clear visualization ofthe hierarchical changes and detailed retinal and choroidal microarchitecture in the macula, while OCTA is more commonly used to observe alterations in capillary density and perfusion. However, these imaging examinations cannot directly reveal the underlying causes of ME or assess the activity level of cytokines within the eye. Cytokine analysis, owing to its capability to directly assess the intraocular milieu, has gained widespread application in recent years for the diagnosis and treatment of uveitis and infectious endophthalmitis [6, 7] .Patients with macular edema may undergo intraocular fluid analysis to accurately determine the cytokine-level etiologies and evaluate the extent of ophthalmic inflammation. Comprehensive data indicate that the expression levels of various cytokines in the aqueous humor of eyes afflicted by CRVO are markedly elevated compared to those in healthy persons, and these levels are distinctly associated with fundus-related symptoms, the severity of ME, and visual prognosis [8, 10] . Nonetheless, due to its invasive nature, cytokine analysis cannot be extensively utilized in clinical settings. Combining intraocular fluid testing findings with routine fundus imaging tests might be advantageous. At present, there is scant study regarding the alterations in aqueous cytokines and macular vascular architecture in CRVO-ME patients. The integration of intraocular fluid test results with standard fundus imaging examinations is essential for the precise diagnosis and classification of CRVO-ME, as well as for informing treatment strategies. This study seeks to examine the relationship between intraocular biomarkers and intravascular cytokines in patients with retinal venous obstructive macular edema, develop the biological and imaging connections, and facilitate precise diagnosis and treatment of CRVO-ME. Materials and methods 1. Selection of research subjects: Study Subjects: The study comprised patients with CRVO-ME who attended our ophthalmology department for examination between July 2025 to December 2025 and were scheduled for intravitreal anti-VEGF or corticosteroid injection. The patients' ages varied from 35 to 79 years. All patients received comprehensive medical history interviews and standard preoperative evaluations, which included slit-lamp microscopy, intraocular pressure assessment, fundus photography, OCT, and OCTA. Patients were enrolled based on inclusion and exclusion criteria, comprising a total of 20 cases involving 20 eyes (Fig. 1 ). 1.2 Inclusion criteria and exclusion criteria of the study subjects 1.2.1 Inclusion criteria (Inclusion of the investigator must meet all of the following conditions) ① Fulfill the pertinent diagnostic criteria for CRVO, including flame-shaped superficial retinal hemorrhages within the territory of the occluded vessel, dilated and tortuous vessels, and the presence of cotton wool patches [2, 4] . ② Macular edema verified by OCT (one of the subsequent requirements must be satisfied: 1. Retinal thickening within 500µm from the macula center. 2. Rigid exudates accompanied by neighboring retinal thinning within 500µm of the macular center. 3. Retinal thickening extending at least one optic disc diameter, encompassing any region within one optic disc diameter from the macular center [11] .) ③ No ophthalmic treatment was received before admission. ④ All patients were willing to receive intravitreal injection of anti-VEGF and/or anti-inflammatory drugs. ⑤ Ocular media were clear, without severe cataract, severe vitreous cavity turbidity, or severe vitreous hemorrhage, and the OCT/OCTA signal strength is greater than 6/10. 1.2.2 Exclusion criteria (exclusion if one of the following is present) ① The physical condition is inadequate for imaging assessment, data collecting, and aqueous humor extraction testing. ② The impacted eye has had pharmacological interventions or therapies that could influence the test outcomes within the past 90 days, such as cataract surgery or history of retinal photocoagulation of retina. ③ Eliminate various ocular conditions, such as glaucoma, retinal artery blockage, diabetic retinopathy, etc. ④ Additional associated diseases and physiological factors that may influence the outcomes of intraocular fluid measurement, including hematological disorders, neoplasms, pregnancy, etc. 1.3 Ethical application: According to the Helsinki Declaration, the Ethics Committee of Linyi Peoples Hospital approved the prospective clinical study related to this topic, with approval number YX200628. All participants in the study were informed and signed an informed consent form, and engaged in the diagnostic and therapeutic processes. 2. Research methods 2.1 Case collection and ophthalmic examination 2.1.1 Case collection: Investigate and record the basic information of patients, including but not limited to name, age, gender, past history,, allergy history, diabetes history, hypertension history, past diagnosis and treatment history, etc. 2.1.2 Preoperative routine assessment: chest X-ray, electrocardiogram, blood routine, four coagulation tests, biochemical analysis, screening of infectious markers, etc. Systemic assessment was comprised of a chest X-ray, ECG, complete blood count, coagulation, biochemical analysis. 2.1.3 Ophthalmological examination (1) Routine ophthalmological examination: use a jet tonometer to measure and record the intraocular pressure of the patient. Use the standard logarithmic visual acuity chart to examine the unaided eye vision and best corrected vision (BCVA). Best-corrected visual acuity (BCVA) was measured using a standard logarithmic chart. Observe and record the anterior segment and fundus under slit lamp. (2)Imaging examination ①Following the exclusion of mydriasis, 0.5% compound tropicamide eye drops should be administered to achieve complete ocular dilation 30 minutes prior to the examination. ② Fundus color photography: Employing the Japanese TOPCON TRC-NW400 fundus camera, patients maintain a direct gaze. The systems entrance pupil and exit pupils are both projected onto the patient’s pupil area, obtaining fundus images of the posterior pole (including the optic disc and macula) at angles ranging from 40°to 55°for each eye. Wide-angle photography is necessary. The position for taking photos should center on the midpoint of the line connecting the optic disc and macula, with the optic disc positioned vertically and centered, and the optic disc and macula aligned horizontally, capturing the posterior pole with optimal field coverage. Precise focusing necessitates that, aside from elements like refractive media opacity, the optic disc, retinal nerve fiber layer, and retinal arteries must be distinctly observable in the fundus image [12] . ③ FFA Examination: The FFA examination is performed using the Spectra Lis HRA fundus fluorescein angiography device from Heidelberg, Germany. A minimal quantity of sodium fluorescein is administered for an allergy test to rule out people with AN allergic to sodium fluorescein. Upon concluding the preparation, the examination commences with a 5-second countdown before to administering 3 ml of 10% sodium fluorescein solution. Images are captured sequentially during the arterial phase, arterial phase, arteriovenous phase, venous phase, late venous phase, and late post-venous phase of the fundus, encompassing the posterior pole, superior, nasal superonasal, nasal inferior, inferior, temporal inferior, temporal superior, and temporal superior regions of the fundus [13] . ④ OCT, OCTA Examination: Employ Zeiss Cirrus HD-OCT 5000 to assess retinal thickness, alterations among retinal layers, and the shape of macular edema. Scanning method: After the patient sits comfortably, adjust the height of the examination headrest and instruct the patient fixated on the central target, patients were instructed to maintain fixation to reduce motion artifacts. Use HD mode to select horizontal (from temporal to nasal) and vertical (from bottom to top) lines for linear scanning through the fovea centralis. The scan length measures 6.0 mm, please adjust the focal point and other parameters accordingly. Once the scan image is clear, adjust the central scanning line to intersect the fovea centralis and capture a photograph for archival purposes. Utilize the integrated measuring tool of the Cirrus system to assess the retinal thickness (CRT) at the fovea centralis three times in both horizontal and vertical orientations, then compute the mean value as the final outcome (Fig. 2 ). CRT was measured three times and averaged; SCP vessel density and FAZ area were quantified using built-in software. Subsequently, perform a retinal SS-OCTA examination with a scan range of 6 mm × 6 mm centered on the fovea centralis. The device's integrated software autonomously detects and records images inside a 6 mm diameter circle centered on the fovea centralis for storage. The system then measures the vascular density (VD) and foveal avascular zone (FAZ)in the superficial retinal capillary plexus (SCP) within 6 mm of the fovea centralis in the affected eye [14] ( Fig. 3 to Fig. 4 ).To ensure data consistency, all examinations were completed by one doctor at the consistent time of day. 2.2 Anterior chamber paracentesis and vitreous cavity drug injection 2.2.1 Preoperative preparation Administer levofloxacin eye drops for instillation, 1–2 drops per time, 4 times per day, for 3 days. On the day of the surgery, use no less than 6 times before the procedure. Clean the conjunctival sac with physiological saline solution to ensure ocular surface sterility. Thirty minutes before surgery, frequently instill 0.5% compound tropicamide eye drops into both eyes to dilate the pupils, confirming that the pupils have fully dilated. Upon the patient's entry into the operating room, provide lidocaine hydrochloride eye drops for topical anesthesia in the waiting area, every 5 minutes, for a total of three applications. 2.2.2 Anterior chamber paracentesis to extract aqueous humour cytokine The patient was positioned supine, and routine preoperative disinfection and draping are performed. Under the operating microscope, a 29G injection needle is chosen to penetrate through the transparent limbus, with the needle tip oriented away from the pupil area, ensuring that the bevel of the needle points toward the corneal endothelium (usually entering at the 11 o’clock position and moving toward the 1 o’clock position). The needle penetrates roughly 1mm into the corneal layer before entering the anterior chamber in alignment with the iris. The assistant gradually retracts the syringe plunger outward to aspirate 0.05 ~ 0.1ml of aqueous humor before removing the needle tip. Alternatively, the syringe plunger may be withdrawn prior to puncture, enabling the intraocular pressure to propel the aqueous humor into the needle tube. The latter can avoid the instability of pulling the piston to draw liquid, thus reducing the possibility of injuring crystals. In the implementation process of this project, most of the extraction methods were selected and found to have extremely high stability, which avoided the variability in manual aspiration to a certain extent. To ensure data consistency,this step was completed by one doctor at the consistent time of day. 2.2.3 Intravitreal drug injection Subsequent to anterior chamber paracentesis, execute intravitreal medication injection. The injection location is designated in the flat region of the temporal ciliary body, roughly 3.5 to 4.0 mm posterior to the limbus. Utilize a 29G syringe to insert the needle vertically penetrate the scleral wall towards the ocular center, and gradually administer the medication. The puncture site will close autonomously following the injection. Monitor for consequences like subconjunctival hemorrhage or vitreous incarceration. Administer levofloxacin ointment to the conjunctival sac and shield the eye with gauze. 2.3 C ytokine examination Retrieve the collected aqueous humor and promptly transfer it to the inspection center-80° refrigerator for freezing. The inspection center employs flow liquid phase multiplex protein quantitative detection technology (BD CBA) to ascertain the amounts of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in the aqueous humor and cytokine concentrations were quantified and recorded.. 2.4 Regular follow-up Gather and document all patients baseline data before treatment, as well as BCVA, intraocular pressure, OCT, OCTA macular morphology, and fundus photography at 1 week, 2 weeks, and 1 month after the first intravitreal drug injection. Monitor postoperative adverse reactions and assess anterior segment responses and fundus status following treatment. During follow-up visits, if exhibit elevated increased intraocular pressure or subconjunctival bleeding, promptly address the symptoms and document them appropriately. 3. Statistical analysis Statistical analysis was conducted using SPSS 26.0. Quantitative data (such as age, imaging data, and aqueous humor cytokine concentrations) were presented as mean ± standard deviation. This study indicates that OCT and OCTA quantitative metrics in the macular region are linear continuous variables associated with intraocular fluid indicators. The relationship between these two sets of indicators was examined using Pearson correlation analysis, with P < 0.05 considered statistically significant. Results 1. General information on the subjects of study ( Table ) Table 1 Information on the patients Table 1 Order Project Age Sex Eye BCVA CRT (µm) FAZ (mm 2 ) SCP-VD (%) IL−6 (pg/ml) IL−8 (pg/ml) VEGF (pg/ml) VCAM (pg/ml) PGF (pg/ml) MCP−1 (pg/ml) 1 49 M L 0.5 686 0.496 37.21 165.4 68.2 123.6 2354.1 65.3 693.2 2 35 M L 1 368 0.432 42.12 40.3 18.7 191 104.8 42.1 639.5 3 79 F R 0.05 611 0.515 38.16 248.9 27.2 85.0 157.0 62.0 414.5 4 53 M 1 0.2 672 0.382 39.42 81.3 44.7 68.5 1219.4 67.0 712.5 5 60 F R 0.05 812 0.402 37.15 213.5 52.6 93.1 1942.9 53.5 852.4 6 54 M L 0.6 466 0.483 40.18 332.1 16.5 85.1 920.3 52.5 541.3 7 73 M L 0.6 681 0.490 37.86 93.4 18.2 221.8 53.4 104 610.2 8 65 M L 0.02 1017 0.532 38.15 277.6 67.5 452.7 793.2 117.5 682.1 9 65 F L 0.15 801 0.458 39.42 247.3 33.4 98.6 1965.3 67.0 586.2 10 51 F R 0.6 306 0.412 41.68 27.9 19.6 48.0 469.8 26.5 612.7 11 59 M R 0.2 423 0.371 40.23 165.4 75.9 51.6 7980 97.0 1101.5 12 54 F L 0.01 663 0.542 39.56 90.8 44.1 105.6 5235.8 87.0 772.4 13 37 F L 0.5 691 0.475 38.71 80.4 15.8 57.6 1585.9 65.5 974.1 14 37 M L 0.4 395 0.383 41.26 146.8 17.7 88.6 3817.7 80.5 273.1 15 58 M 1 0.15 560 0.431 40.98 52.7 16.6 22.1 642.3 47.0 347.1 16 58 F R 0.05 625 0.387 38.42 235.0 62.3 123.6 2364.5 67.3 512.3 17 76 F L 0.4 310 0.453 41.61 53.6 56.0 22.4 7911.9 102.0 658.0 18 52 F R 0.05 495 0.379 40.95 214.6 26.2 39.1 939.0 101.0 516.20 19 53 M R 0.2 478 0.502 40.12 156.8 74.8 142.3 2431.0 153.2 498.1 20 63 M L 0.4 396 0.413 41.31 99.3 16.5 34.0 652.1 72.6 356.3 CRVO-ME: center retinalvein occlusive-macular edema; CRT: central retinal thickness; FAZ: foveal avascular area;SCP-VD: superficial capillary plexus-vessel density ; IL: interleukin; VEGF: vascular endothelial growth factor; VCAM: vascular cell adhesion molecule; PGF: placental growth factor; MCP: monocyte chemotactic protein In this study, 20 cases of CRVO patients and 20 eyes were selected, with an average age of onset ranging from 35 to 79 years old, with a mean age of 56.55 ± 12.00 years. Among them, 11 were male and 9 were female; 7 eyes were in the right eye and 13 in the left eye. All patients had not received vitreous injection or fundus laser therapy before. 2. CRVO-ME patient CRT,FAZ and SCP-VD test results in this study ( Table ) In this study, the average CRT of 20 eyes of CRVO-ME patients was (572.80 ± 186.57) µm; FAZ area was (0.45 ± 0.06) mm 2 and SCP-VD was (39.73 ± 1.56)%。 3. Results of aqueous cell factor detection in CRVO-ME patients in this study ( Table ) In this study, the average concentrations of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in 20 eyes of patients were (151.16 ± 88.61) pg/ml, (38.63 ± 22.29) pg/ml, (107.72 ± 96.76) pg/ml, (2177.02 ± 2357.69) pg/ml, (76.53 ± 29.48) pg/ml, and (617.69 ± 205.87) pg/ml, respectively. 4. Correlation analysis of the concentration of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in the aqueous humor of CRVO-ME patients with CRT, FAZ and SCP-VD (Attached Fig. 5 to Fig. 7 ). This study analyzed the concentration of aqueous humor and intraocular fluid variables in 20 eyes from 20 individuals with CRVO-ME, revealing results by Pearson correlation analysis: CRT had a substantial positive correlation with the amounts of aqueous humor cytokines IL-6 and VEGF (r = 0.450,0.593, P 0.05). The area of FAZ exhibited a strong positive correlation with the concentration of VEGF (r = 0.489, P 0.05). The SCP-VD exhibited a strong negative correlation with IL-6 (r=-0.462, P 0.05) ( Table 2 ). Table 2 Correlation analysis between CRT, FAZ area, SCP-VD and cytokine concentration in aqueous humor of CRVO-ME patients Aqueous cell factor CRT FAZ area SCP -VD R P R P R P IL-6 0.450 0.047 0.174 0.464 -0.462 0.040 IL-8 0.365 0.114 0.277 0.237 -0.171 0.471 VEGF 0.593 0.006 0.489 0.029 -0.391 0.088 VCAM -0.261 0.267 -0.120 0.614 0.162 0.495 PGF 0.137 0.566 0.286 0.222 -0.101 0.672 MCP-1 0.260 0.268 0.024 0.921 -0.322 0.166 CRVO-ME: retinal center vein occlusive macular edema; CRT: central retinal thickness; SCP: superficial capillary plexus; FAZ: foveal avascular area; IL: interleukin; VEGF: vascular endothelial growth factor; VCAM: vascular cell adhesion molecule; PGF: placental growth factor; MCP: monocyte chemotactic protein Discussion The exploration of representative imaging biomarkers, the integration of intraocular fluid with fundus imaging biomarkers to evaluate the condition and forecast the prognosis of ME and its underlying diseases, as well as the optimization of treatment strategies, will provide substantial guidance for the management of ME and its associated conditions. Particularly in the initial phases of ME, this thorough evaluation method enhances the understanding of the diseases pathogenesis and facilitates the early identification of refractory ME, thereby providing essential evidence for clinical treatment, forecasting vision recovery, and allowing for personalized precision therapy. This consequently establishes a scientific foundation for the selection of clinical treatment techniques. Early care can significantly decelerate or avert the advancement of ME and its underlying conditions, improve patients visual prognosis, and enhance their quality of life. To avoid serious complications that may arise from vitreous puncture and aspiration (such as vitreous incarceration) [15] , this study selected anterior chamber aqueous humor from ME patients as the research subject. This study selected CRVO-ME patients, the most prevalent and representative examples of ME, to examine the association between aqueous humor cytokines and imaging biomarkers. Twenty cases (20 eyes) from CRVO-ME patients were selected for testing the concentrations of IL-6, IL-VEGF, VCAM, PGF, and MCP-1. The OCT and OCTA findings were correlated with clinically accessible and quantified fundus imaging results to enhance the precision of ME treatment. This study selects fundus imaging markers selected are CRT, SCP-VD, and FAZ, which possess substantial clinical significance and are readily accessible. Such parameters are periodically measured in the ophthalmology clinics, which makes them convenient biomarkers when it comes to creating disease progression and treatment response. CRT is a metric employed to objectively evaluate the extent of macular thickening by measuring the vertical distance between the inner limiting membrane of the macular fovea and the retinal pigment epithelium basement membrane in OCT images [16] .This metric can objectively and intuitively evaluate the extent of macular thickness, which is essential for the diagnosis and monitoring of ME. The CRT of eyes with CRVO-ME was measured at (572.80 ± 186.57) µm, which is much greater than the normal upper limit of 250 µm, indicating considerable macular thickening in individuals. Nonetheless, we discovered that CRVO-ME patients with SRD, despite exhibiting increased central macular thickness (CMT) and foveal choroidal thickness (SFCT), presented with reduced central retinal thickness (CRT). Consequently, investigating the link between CRT and intraocular fluid may provide inaccuracies in research with limited sample sizes. The central fovea of the macula is the most sensitive region of vision, characterized by a few hundred microns of avascular tissue in its core. This area is called the macula central Fovea avascular zone (FAZ) [17] .The dimensions of FAZ are directly correlated with visual prognosis. The occurrence of lesions significantly impacts central vision and visual acuity. Damage to retinal microcirculation and capillary ischemia in RVO result in the enlargement of FAZ area. Simultaneously, it was determined that FAZ has heightened sensitivity to variations in blood flow and can indicate the condition of retinal capillaries [18] .A substantial quantity of samples indicated that in patients, eyes with an enlarged FAZ region exhibited diminished vision, and a significant negative association existed between FAZ area and visual acuity [19] .The FAZ area in the affected eyes of this cohort with CRVO-ME it was (0.45 ± 0.06) mm², greatly beyond the normal range (0.25 ~ 0.30) mm². Nevertheless, the FAZ region is intricately linked to axial length and ocular growth, rendering it very imprecise when utilized as a solitary variable for quantitative assessment. However, enlarging the FAZ continues to be a potent predictor of visual poor prognosis and needs to be incorporated with the rest of the imaging biomarkers. The retinal superficial capillary plexus-vessel density (SCP-VD) is defined as the ratio of vessels to the entire measured area, indicating retinal blood flow perfusion [20] .Lee [21] Studies have found that the integrity of the peripapillary choroidal plexus (DCP) is closely associated with the effectiveness of anti-VEGF medications in the treatment of ME. The extent of DCP loss may serve as a significant predictive marker for the likelihood of a successful response to anti-VEGF therapy. It has been proven that in eyes with DME, there exists a substantial negative association between SCP vascular density and visual acuity. In cases of moderate to severe CRVO, the presence of retinal edema, vitreous opacity, and vitreous hemorrhage considerably skews the quantitative data of deep DCP vascular density, complicating accurate measurement. Consequently, this study designated SCP as the subject of investigation. In this group, the SCP blood flow density in eyes with CRVO-ME was (39.73 ± 1.56)% lower than in normal eyes, indicating that the damage to SCP in ME eyes is more severe. Moreover, the high reflectivity point (hyperreflective dots, HRD) on OCT appears as discrete high reflectivity particles with a diameter of 20–30µm in OCT. It is presently thought that it emanates from inflammatory activated microglia [22] . Prior research has established that microglia reside in the inner layer of retina as an innate immune cell, which get activated with retinal injury. Certain microglia will migrate to the outer retinal layer and aggregate to contribute to the synthesis of pro-inflammatory cytokines [23] .HRD was linked to the integrity of light receptors on OCT and visual prognosis [24] .Recently, Professor Yao Jin’s team in China discovered a substantial correlation between the elevation of inflammatory components and the quantity of HRD through the analysis of several cases .Moon [25] demonstrated that eyes with SND exhibited increased IL-6 levels, signifying active inflammation, and that eyes with SND coupled with DME responded significantly to dexamethasone implants, supporting the utilization of dexamethasone implants in patients with SND .In the future, other biological indicators will be investigated for diagnosing patients and assessing the course of intraocular diseases. Among the cytokines in the eye, six representative cytokines IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 were selected to obtain rapid test results by flow cytometer. IL-6, as a representative of inflammatory factors, is pivotal in expediting the inflammatory response, enhancing vascular permeability, producing vascular leakage, and stimulating other cytokines (such as VEGF factor and ICAM-1 factor) [26] .IL-6 serves as a catalyst for inflammatory responses by facilitating immunological reactions, chiefly through the promotion of B cell development and antibody synthesis, alongside the induction of T cell activation, proliferation, and differentiation. IL-6 enhances endothelial cell permeability and vascular leakage by suppressing the expression of tight junction proteins occludin and ZO-1, hence widening the intercellular gaps [27] .Glucocorticoids (such as dexamethasone implant) improve refractory ME by inhibiting inflammatory factors such as IL-6 and TNF-α. Research indicates that the combination of anti-VEGF and subfascial sac hormone therapy can synergistically diminish aqueous levels of VEGF and IL-6, hence enhancing efficacy [28] . This study found a positive association between IL-6 and CRT, and a negatively correlated between IL-6 and SCP-VD in patients with CRVO-ME, indicating that IL-6 may be a contributing factor to the progression of CRVO-ME and is significantly associated with vascular damage. This result confirms the relevance of targeting the VEGF as well as IL-6 pathways, which could be achieved with the help of anti-VEGF therapy combining with corticosteroids. IL-8, a prevalent chemotaxis, can induce the chemotaxis of neutrophils, T lymphocytes and eosinophils, signifying the presence of intraocular inflammation [29] . During prolonged ischemia and hypoxia in the eye, IL-8 is generated to inhibit neutrophils and T cells, exhibiting a favorable correlation with VEGF levels, which together facilitate the onset and progression of ME. Yoshida et al [30] Using control experiments, it was found that the level of IL-8 in the vitreous body of patients with retinal neovascularization is significantly elevated. In retinas exhibiting neovascularization has occurred, immunostaining for IL-8 was observed in vascular endothelial cells and glial cells, indicating that IL-8 plays a role in neovascularization. Wu F et al [31] In individuals with macular edema, notable elevations in IL-8 levels were detected in the vitreous and aqueous humor, and these IL-8 levels associated with the severity of macular edema and the extent of glial cell obstruction in retinal arteries. This study found that IL-8 concentrations did not exhibit significant relationships with CRT, FAZ area, or SCP blood flow density, suggesting a minimal impact. VEGF is the cytokine most intimately associated with the onset of macular edema, which alters the cellular microenvironment, enhances vascular permeability, facilitates the migration and proliferation of vascular endothelial cells, and induces angiogenesis [32] .Its concentration indicates the extent of neovascularization in the eye and is presently the most potent angiogenic factor identified. This investigation revealed that in CRVO, both CRT and FAZ areas had a strong positive correlation with VEGF content in the aqueous humor, underscoring the pivotal role of VEGF in the pathophysiology of macular edema. This outcome corroborates the efficacy of anti-VEGF agents as a primary treatment for CRVO-ME, hence reinforcing the significance of VEGF as a therapeutic target. VCAM, a cell adhesion molecule, is linked to the rupture of blood eye barrier, and elevated titers signify the existence of intraocular tissue edema [33] . It is a sign of vascular endothelial activation injury and is crucial for the adherence of inflammatory cells. It is frequently excessively heightened in chronic inflammation [34] . In this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area or SCP blood flow density, suggesting it had no substantial impact on RVO. PGF can stimulate endothelial cell proliferation and migration, anti-endothelial cell apoptosis, increase vascular permeability, enhance the biological activity of low concentration of VEGF, is an important angiogenic factor involved in the angiogenesis of various malignancies [35] . In this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area, or SCP blood flow density, suggesting that its impact on CRVO was negligible. MCP-1, a significant pro-inflammatory agent within the chemokine family, contributes to the course of CRVO by mediating inflammation, facilitating the chemotaxis of lymphocytes and monocytes, activating signaling pathways, and promoting angiogenesis [36] . MCP-1 attracts chemotactic inflammatory cells, including monocytes and macrophages to accumulate in the retinal capillaries. The narrow width of the capillaries predisposes them to obstruction, while elevated hydrostatic pressure results in vascular leakage and the development of retinal aneurysms, hence exacerbating the evolution of ME from numerous perspectives [37] . However, in this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area or SCP blood flow density, suggesting it had no substantial impact on CRVO. The findings of this study demonstrate that in ME pathophysiology, the expression of local and systemic inflammatory factors and chemokines is markedly elevated, instigating widespread inflammatory responses. This inflammatory response results in damage to retinal microvessels and structures, undermines the primary immune defense in the retina, the BRB, and further intensifies the cycle of macular edema while facilitating the development of aberrant neovascularization [38] . The findings of this study are mostly aligned with the experimental studies conducted internationally [36] .The relationship between detection outcomes and readily obtainable, measurable fundus imaging data can be elucidated from many perspectives, offering guidance for the targeted therapy of ME. The aging process is progressively intensifying, hence exacerbating the prevalence of CRVO-ME. The deterioration of patients' vision significantly diminishes their quality of life and impairs the stable and healthy progression of social economy. Efforts have been undertaken both domestically and internationally to investigate the optimal treatment for ME. The prevalence of patients with refractory macular edema is rising. Within 2 years of receiving monthly anti-VEGF treatments, the probability of refractory ME can reach nearly 40%. Nonetheless, the majority of patients with resistant macular edema have attained significant therapeutic outcomes with the substitution of various anti-VEGF agents, intravitreal injections of hormones, peripapillary micro-photocoagulation, vitrectomy+ endophakic extraction. Patients will gain greater advantages from the accurate diagnosis of refractory macular edema by the utilization of biological markers in imaging, resulting in early vision enhancement. Prompt identification of these individuals via imaging and the prompt implementation of targeted therapy can optimize the avoidance of additional visual deterioration. Anti-VEGF pharmacotherapy has been clinically substantiated for the treatment of conditions such as RVO. RVO has a definitive efficacy in enhancing vision and markedly surpasses conventional retinal laser photocoagulation in alleviating macular edema. The medication results in fewer adverse events; initiating it earlier improves long-term visual prognosis and reduces the duration of treatment necessary. Nonetheless, a significant proportion of resistant patients with edema continue to have a delayed or no response to anti-VEGF medications. Corticosteroids have been demonstrated to be particularly beneficial in the treatment ME and are now extensively utilized for the anti-inflammatory management of ocular diseases. In the current era of prevalent intravitreal injections of anti-VEGF and anti-inflammatory agents, monoclonal antibodies, bispecific antibodies, fusion proteins, small molecule antibodies, and single-chain antibody fragment therapeutics are progressively appearing. ‌Aflibercept exhibits multiple mechanisms of action, targeting both anti-VEGF and anti-PLGF pathways [39] . Simultaneously, Faricimab has dual effects of anti-VEGF and anti-Ang-2 [40] . Bevacizumab is a complete VEGF-A inhibitor, characterized by its molecular weight of 26kDa and significant tissue penetration, which enhances its efficacy in eliminating IRF and SRF [41] . Aodi, as a sustained-release agent of dexamethasone, can enhance the inflammatory response in the vitreous cavity and sustain its impact for 3–6 months [42] . Consequently, a varied array of therapeutic agents and protocols provides patients with increased alternatives while posing new obstacles for clinicians in their diagnostic and therapeutic decisions. Investigating accurate ME diagnosis and treatment strategies entails utilizing fundus imaging markers to deduce the therapeutic activity within the patient's eye, selecting optimal medications to enhance vision, identifying more efficacious treatments, augmenting diagnostic precision, and improving patient outcomes. This study possesses some limitations: (1) The participants discussed in this paper were examined prior to intravitreal medication injection therapy. Phase II clinical trials are presently undertaking long-term follow-ups on patients, incorporating multicenter, large-sample investigations, prolonging the observation time, and integrating more detailed and comprehensive imaging indicators for correlation analysis, including DRIL, IRC, and SRF. The correlation between these disorders will be assessed, and a predictive model for macular edema lesions will be developed. Measures will be undertaken to integrate many elements, increase vigilance, and swiftly execute actions to avert or postpone advancement, thus facilitating early prevention and management of the disease. (2) Due to extensive data from both domestic and international sources indicating that RVO patients have higher levels of aqueous humour cytokine compared to normal eyes [43] . There is an agreement both domestically and internationally that the alterations in the fundus imaging of patients markedly differ from the quantitative analysis of normal eyes [2,16,44] . This study attempts to evaluate the association between the two, hence, a healthy control group was not included in this study. Our study team is presently performing a correlation analysis between intraocular fluids, specifically DME and AMD and imaging biomarkers, which will be subsequently compared and discussed. (3) In our study, the correlation analysis between cytokines and imaging biomarkers was conducted using univariate correlation analysis. During the development and treatment of ME, a vast array of molecular pathways is implicated, and multivariate and multifactorial correlation analysis is anticipated to yield more substantial evidence of relationship. Imaging-based biological markers, in conjunction with intraocular fluid analysis, can substantially aid in directing treatment and forecasting results for ME patients, enhancing management strategies and increasing patient adherence to treatment protocols. Integrating OCT, OCTA, and intraocular cytokine analysis, artificial intelligence analyzes fundus imaging images to automatically correlate cytokine profiles, achieving precise typing. Predictive models are developed by integrating many characteristics to facilitate early prevention and prompt intervention, therefore averting or postponing the advancement of ME and its associated disorders. Fundus imaging investigations of macular edema and intraocular cytokine analysis yield essential insights into their etiology and enhance treatment strategies. The integration of dynamic imaging monitoring with molecular biology approaches offers potential for individualized therapy and enhanced patient outcomes. Conclusions (1)Cytokine expression was associated with the macular structure of the macula and the extent of microvascular damage surrounding the macula. (2)The biological indicators could improve therapy decision-making and precision medicine. (3)Future management of CRVO-ME should encompass not just anti-VEGF medication but also targeted anti-inflammatory agents, and additional therapeutic modalities. Declarations Acknowledgements Not applicable. Disclosure statement No potential conflict of interest was reported by the author(s). Data availability The data that support the findings of this study are available from the authors. Funding This project is not funded by any grant. Ethics declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was reviewed by Linyi People's Hospital. All of the participants signed informed consent forms. Consent for publication Not applicable. Author Contribution Jie Gao, Tao Wangprimarily responsible for literature retrieval, data processing, and article writing.Huiwen Pang was responsible for reviewing statistical.Maojuan Feng,Weijie Zhang were responsible for editing and reviewing the articles. References Daruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, Rothschild PR, Omri S, Gélizé E, Jonet L, Delaunay K, De Kozak Y, Berdugo M, Zhao M, Crisanti P, Behar-Cohen F. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 05 May, 2026 Reviewers invited by journal 30 Apr, 2026 Editor assigned by journal 30 Apr, 2026 Editor invited by journal 29 Apr, 2026 Submission checks completed at journal 28 Apr, 2026 First submitted to journal 28 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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density\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-9449389/v1/831d4226a5f45454b20e8292.png"},{"id":108978721,"identity":"f1870346-35fd-4e76-9060-8c11c6014e95","added_by":"auto","created_at":"2026-05-11 11:48:01","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":152493,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between CRT and IL-6 ,IL-,VEGF,VCAM,PGF,MCP-1 in CRVO-ME patients\u003c/p\u003e\n\u003cp\u003eCRVO-ME:center retinalvein occlusive-macular edema;CRT:central retinal \u0026nbsp;hickness;IL:interleukin;VEGF:vascular endothelial growth factor; VCAM:vascular cell adhesion molecule;PGF:placental growth factor;MCP:monocyte chemotactic protein\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-9449389/v1/7c0dabe97bcdebbe9918abcc.png"},{"id":108978722,"identity":"fb472881-55b7-4962-ac97-1f1383db2e58","added_by":"auto","created_at":"2026-05-11 11:48:01","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":111561,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between FAZ area and IL-6,IL-8,VEGF,VCAM,PGF, MCP-1 in CRVO-ME patients\u003c/p\u003e\n\u003cp\u003eCRVO-ME: center retinalvein occlusive-macular edema; FAZ: fovealavascular zone; IL: interleukin; VEGF: vascular endothelial growth factor; VCAM: vascular cell adhesion molecule; PGF:placental growth factor; MCP: monocyte chemotactic protein\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-9449389/v1/58b2a106a3f76a02ade7f6d0.png"},{"id":108978631,"identity":"bda3b554-f730-4bc2-9e95-51722ba6a572","added_by":"auto","created_at":"2026-05-11 11:47:04","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":68995,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between SCP-VD and IL-6,IL-8,VEGF,VCAM,PGF, MCP-1 in CRVO-ME patients\u003c/p\u003e\n\u003cp\u003eCRVO-ME:center retinalvein occlusive-macular edema;SCP-VD:superficial capillary plexus-vessel density;IL:interleukin;VEGF:vascular endothelial growth factor;VCAM:vascular cell adhesion molecule;PGF:placental growth factor;MCP:monocyte chemotactic protein\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-9449389/v1/22140507db7bc5f0842b4f56.png"},{"id":108982253,"identity":"8a34e5a9-6016-4575-b96d-bbf361151546","added_by":"auto","created_at":"2026-05-11 12:24:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4372936,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9449389/v1/af4ded89-5e98-4b37-bf9a-44c7a41c0617.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between aqueous humour cytokine and Imaging Biomarker in CRVO-ME","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMacular edema (ME) is a significant contributor to vision impairment in individuals with Retinal Vein Occlusion (RVO)\u003csup\u003e[1]\u003c/sup\u003e. The prevailing belief is that the primary pathophysiology of the disease involves the disruption of Blood-Retinal Barrier (BRB), resulting in fluid accumulation in the macula, ultimately causing vision loss or even blindness\u003csup\u003e[2]\u003c/sup\u003e. According to recent identifications within fundus imaging and molecular biology, the pathophysiological processes of macular edema, and the control of aqueous humor cytokines (e.g., VEGF, IL-6) in particular has elevated interest. \u003csup\u003e[3]\u003c/sup\u003e.This study aims to investigate the relationship between biomarkers of fundus imaging and cytokine levels in Central retinal vein occlusive - macular edema (CRVO-ME), and to determine their possible usefulness in diagnosis, treatment and prognosis testing.\u003c/p\u003e \u003cp\u003eIn individuals with early CRVO, the buildup of metabolic byproducts within the arteries and the induction of an acidic milieu generate inflammatory mediators that result in leukocyte aggregation, hence producing microcirculatory disturbances in the retina\u003csup\u003e[4]\u003c/sup\u003e. This leads to non-perfused areas in the respective retinal regions, resulting in elevated VEGF levels as a compensatory response. Cytokines concurrently govern cell-to-cell interactions, influence inflammatory responses, engage in immunological responses, and facilitate tissue repair, hence supporting many physiological and pathological processes.\u003c/p\u003e \u003cp\u003eIn recent years, fundus imaging has been increasingly adopted in clinical practice. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) are the primary techniques for assessing the microstructure and pathological alterations of retinal layers and micro-vessels. Due to their non-invasive characteristics, optical coherence tomography has become a common method for detection and evaluation of ME in recent years\u003csup\u003e[1, 4]\u003c/sup\u003e.This non-contact, non-invasive optical imaging diagnostic method can reveal the cross-sectional architecture of the posterior segment of the eye, rendering it useful for examining subtle features such as subretinal fluid (SRF), intraretinal fluid (IRF), retinal inner layer structural disorder (DRIL), and high reflectance foci (HRF). In practical practice, physicians predominantly utilize OCT to perform qualitative and quantitative assessments of the several tissue layers in the macula to diagnose ME lesions. As a vascular imaging technology developed from OCT, OCTA can obtain the morphology and perfusion status of retinal blood, and their blood flow data in real time without invasiveness\u003csup\u003e[5]\u003c/sup\u003e .OCTA can accomplish stratified imaging of retinal and choroidal vessels while quantitatively assessing vascular density and lesion volume.\u003c/p\u003e \u003cp\u003eOCT can provide clear visualization ofthe hierarchical changes and detailed retinal and choroidal microarchitecture in the macula, while OCTA is more commonly used to observe alterations in capillary density and perfusion. However, these imaging examinations cannot directly reveal the underlying causes of ME or assess the activity level of cytokines within the eye. Cytokine analysis, owing to its capability to directly assess the intraocular milieu, has gained widespread application in recent years for the diagnosis and treatment of uveitis and infectious endophthalmitis\u003csup\u003e[6, 7]\u003c/sup\u003e .Patients with macular edema may undergo intraocular fluid analysis to accurately determine the cytokine-level etiologies and evaluate the extent of ophthalmic inflammation. Comprehensive data indicate that the expression levels of various cytokines in the aqueous humor of eyes afflicted by CRVO are markedly elevated compared to those in healthy persons, and these levels are distinctly associated with fundus-related symptoms, the severity of ME, and visual prognosis\u003csup\u003e[8, 10]\u003c/sup\u003e. Nonetheless, due to its invasive nature, cytokine analysis cannot be extensively utilized in clinical settings. Combining intraocular fluid testing findings with routine fundus imaging tests might be advantageous. At present, there is scant study regarding the alterations in aqueous cytokines and macular vascular architecture in CRVO-ME patients. The integration of intraocular fluid test results with standard fundus imaging examinations is essential for the precise diagnosis and classification of CRVO-ME, as well as for informing treatment strategies.\u003c/p\u003e \u003cp\u003eThis study seeks to examine the relationship between intraocular biomarkers and intravascular cytokines in patients with retinal venous obstructive macular edema, develop the biological and imaging connections, and facilitate precise diagnosis and treatment of CRVO-ME.\u003c/p\u003e"},{"header":"Materials and methods","content":"\n\u003ch3\u003e1. Selection of research subjects:\u003c/h3\u003e\n\u003cp\u003eStudy Subjects: The study comprised patients with CRVO-ME who attended our ophthalmology department for examination between July 2025 to December 2025 and were scheduled for intravitreal anti-VEGF or corticosteroid injection. The patients' ages varied from 35 to 79 years. All patients received comprehensive medical history interviews and standard preoperative evaluations, which included slit-lamp microscopy, intraocular pressure assessment, fundus photography, OCT, and OCTA. Patients were enrolled based on inclusion and exclusion criteria, comprising a total of 20 cases involving 20 eyes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e1.2 Inclusion criteria and exclusion criteria of the study subjects\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e1.2.1 Inclusion criteria (Inclusion of the investigator must meet all of the following conditions)\u003c/div\u003e \u003cp\u003e① Fulfill the pertinent diagnostic criteria for CRVO, including flame-shaped superficial retinal hemorrhages within the territory of the occluded vessel, dilated and tortuous vessels, and the presence of cotton wool patches \u003csup\u003e[2, 4]\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003e② Macular edema verified by OCT (one of the subsequent requirements must be satisfied: 1. Retinal thickening within 500\u0026micro;m from the macula center. 2. Rigid exudates accompanied by neighboring retinal thinning within 500\u0026micro;m of the macular center. 3. Retinal thickening extending at least one optic disc diameter, encompassing any region within one optic disc diameter from the macular center\u003csup\u003e[11]\u003c/sup\u003e .)\u003c/p\u003e \u003cp\u003e③ No ophthalmic treatment was received before admission.\u003c/p\u003e \u003cp\u003e④ All patients were willing to receive intravitreal injection of anti-VEGF and/or anti-inflammatory drugs.\u003c/p\u003e \u003cp\u003e⑤ Ocular media were clear, without severe cataract, severe vitreous cavity turbidity, or severe vitreous hemorrhage, and the OCT/OCTA signal strength is greater than 6/10.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e1.2.2 Exclusion criteria (exclusion if one of the following is present)\u003c/div\u003e \u003cp\u003e① The physical condition is inadequate for imaging assessment, data collecting, and aqueous humor extraction testing.\u003c/p\u003e \u003cp\u003e② The impacted eye has had pharmacological interventions or therapies that could influence the test outcomes within the past 90 days, such as cataract surgery or history of retinal photocoagulation of retina.\u003c/p\u003e \u003cp\u003e③ Eliminate various ocular conditions, such as glaucoma, retinal artery blockage, diabetic retinopathy, etc.\u003c/p\u003e \u003cp\u003e④ Additional associated diseases and physiological factors that may influence the outcomes of intraocular fluid measurement, including hematological disorders, neoplasms, pregnancy, etc.\u003c/p\u003e \u003cp\u003e 1.3 Ethical application: According to the Helsinki Declaration, the Ethics Committee of Linyi Peoples Hospital approved the prospective clinical study related to this topic, with approval number YX200628. All participants in the study were informed and signed an informed consent form, and engaged in the diagnostic and therapeutic processes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2. Research methods\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Case collection and ophthalmic examination\u003c/h2\u003e \u003cp\u003e2.1.1 Case collection: Investigate and record the basic information of patients, including but not limited to name, age, gender, past history,, allergy history, diabetes history, hypertension history, past diagnosis and treatment history, etc.\u003c/p\u003e \u003cp\u003e2.1.2 Preoperative routine assessment: chest X-ray, electrocardiogram, blood routine, four coagulation tests, biochemical analysis, screening of infectious markers, etc. Systemic assessment was comprised of a chest X-ray, ECG, complete blood count, coagulation, biochemical analysis.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.1.3 Ophthalmological examination\u003c/h2\u003e \u003cp\u003e(1) Routine ophthalmological examination: use a jet tonometer to measure and record the intraocular pressure of the patient. Use the standard logarithmic visual acuity chart to examine the unaided eye vision and best corrected vision (BCVA). Best-corrected visual acuity (BCVA) was measured using a standard logarithmic chart. Observe and record the anterior segment and fundus under slit lamp.\u003c/p\u003e \u003cp\u003e(2)Imaging examination\u003c/p\u003e \u003cp\u003e①Following the exclusion of mydriasis, 0.5% compound tropicamide eye drops should be administered to achieve complete ocular dilation 30 minutes prior to the examination.\u003c/p\u003e \u003cp\u003e② Fundus color photography: Employing the Japanese TOPCON TRC-NW400 fundus camera, patients maintain a direct gaze. The systems entrance pupil and exit pupils are both projected onto the patient\u0026rsquo;s pupil area, obtaining fundus images of the posterior pole (including the optic disc and macula) at angles ranging from 40\u0026deg;to 55\u0026deg;for each eye. Wide-angle photography is necessary. The position for taking photos should center on the midpoint of the line connecting the optic disc and macula, with the optic disc positioned vertically and centered, and the optic disc and macula aligned horizontally, capturing the posterior pole with optimal field coverage. Precise focusing necessitates that, aside from elements like refractive media opacity, the optic disc, retinal nerve fiber layer, and retinal arteries must be distinctly observable in the fundus image\u003csup\u003e[12]\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003e③ FFA Examination: The FFA examination is performed using the Spectra Lis HRA fundus fluorescein angiography device from Heidelberg, Germany. A minimal quantity of sodium fluorescein is administered for an allergy test to rule out people with AN allergic to sodium fluorescein. Upon concluding the preparation, the examination commences with a 5-second countdown before to administering 3 ml of 10% sodium fluorescein solution. Images are captured sequentially during the arterial phase, arterial phase, arteriovenous phase, venous phase, late venous phase, and late post-venous phase of the fundus, encompassing the posterior pole, superior, nasal superonasal, nasal inferior, inferior, temporal inferior, temporal superior, and temporal superior regions of the fundus\u003csup\u003e[13]\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003e④ OCT, OCTA Examination: Employ Zeiss Cirrus HD-OCT 5000 to assess retinal thickness, alterations among retinal layers, and the shape of macular edema. Scanning method: After the patient sits comfortably, adjust the height of the examination headrest and instruct the patient fixated on the central target, patients were instructed to maintain fixation to reduce motion artifacts. Use HD mode to select horizontal (from temporal to nasal) and vertical (from bottom to top) lines for linear scanning through the fovea centralis. The scan length measures 6.0 mm, please adjust the focal point and other parameters accordingly. Once the scan image is clear, adjust the central scanning line to intersect the fovea centralis and capture a photograph for archival purposes. Utilize the integrated measuring tool of the Cirrus system to assess the retinal thickness (CRT) at the fovea centralis three times in both horizontal and vertical orientations, then compute the mean value as the final outcome (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). CRT was measured three times and averaged; SCP vessel density and FAZ area were quantified using built-in software. Subsequently, perform a retinal SS-OCTA examination with a scan range of 6 mm \u0026times; 6 mm centered on the fovea centralis. The device's integrated software autonomously detects and records images inside a 6 mm diameter circle centered on the fovea centralis for storage. The system then measures the vascular density (VD) and foveal avascular zone (FAZ)in the superficial retinal capillary plexus (SCP) within 6 mm of the fovea centralis in the affected eye\u003csup\u003e[14]\u003c/sup\u003e ( Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e to Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).To ensure data consistency, all examinations were completed by one doctor at the consistent time of day.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Anterior chamber paracentesis and vitreous cavity drug injection\u003c/h2\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Preoperative preparation\u003c/h2\u003e \u003cp\u003eAdminister levofloxacin eye drops for instillation, 1\u0026ndash;2 drops per time, 4 times per day, for 3 days. On the day of the surgery, use no less than 6 times before the procedure. Clean the conjunctival sac with physiological saline solution to ensure ocular surface sterility. Thirty minutes before surgery, frequently instill 0.5% compound tropicamide eye drops into both eyes to dilate the pupils, confirming that the pupils have fully dilated. Upon the patient's entry into the operating room, provide lidocaine hydrochloride eye drops for topical anesthesia in the waiting area, every 5 minutes, for a total of three applications.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Anterior chamber paracentesis to extract aqueous humour cytokine\u003c/h2\u003e \u003cp\u003eThe patient was positioned supine, and routine preoperative disinfection and draping are performed. Under the operating microscope, a 29G injection needle is chosen to penetrate through the transparent limbus, with the needle tip oriented away from the pupil area, ensuring that the bevel of the needle points toward the corneal endothelium (usually entering at the 11 o\u0026rsquo;clock position and moving toward the 1 o\u0026rsquo;clock position). The needle penetrates roughly 1mm into the corneal layer before entering the anterior chamber in alignment with the iris. The assistant gradually retracts the syringe plunger outward to aspirate 0.05\u0026thinsp;~\u0026thinsp;0.1ml of aqueous humor before removing the needle tip. Alternatively, the syringe plunger may be withdrawn prior to puncture, enabling the intraocular pressure to propel the aqueous humor into the needle tube. The latter can avoid the instability of pulling the piston to draw liquid, thus reducing the possibility of injuring crystals. In the implementation process of this project, most of the extraction methods were selected and found to have extremely high stability, which avoided the variability in manual aspiration to a certain extent. To ensure data consistency,this step was completed by one doctor at the consistent time of day.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 Intravitreal drug injection\u003c/h2\u003e \u003cp\u003eSubsequent to anterior chamber paracentesis, execute intravitreal medication injection. The injection location is designated in the flat region of the temporal ciliary body, roughly 3.5 to 4.0 mm posterior to the limbus. Utilize a 29G syringe to insert the needle vertically penetrate the scleral wall towards the ocular center, and gradually administer the medication. The puncture site will close autonomously following the injection. Monitor for consequences like subconjunctival hemorrhage or vitreous incarceration. Administer levofloxacin ointment to the conjunctival sac and shield the eye with gauze.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.3 \u003cb\u003eC\u003c/b\u003eytokine examination\u003c/h2\u003e \u003cp\u003eRetrieve the collected aqueous humor and promptly transfer it to the inspection center-80\u0026deg; refrigerator for freezing. The inspection center employs flow liquid phase multiplex protein quantitative detection technology (BD CBA) to ascertain the amounts of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in the aqueous humor and cytokine concentrations were quantified and recorded..\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Regular follow-up\u003c/h2\u003e \u003cp\u003eGather and document all patients baseline data before treatment, as well as BCVA, intraocular pressure, OCT, OCTA macular morphology, and fundus photography at 1 week, 2 weeks, and 1 month after the first intravitreal drug injection. Monitor postoperative adverse reactions and assess anterior segment responses and fundus status following treatment. During follow-up visits, if exhibit elevated increased intraocular pressure or subconjunctival bleeding, promptly address the symptoms and document them appropriately.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e3. Statistical analysis\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was conducted using SPSS 26.0. Quantitative data (such as age, imaging data, and aqueous humor cytokine concentrations) were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. This study indicates that OCT and OCTA quantitative metrics in the macular region are linear continuous variables associated with intraocular fluid indicators. The relationship between these two sets of indicators was examined using Pearson correlation analysis, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\n\u003ch3\u003e1. General information on the subjects of study ( Table )\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInformation on the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003cp\u003eOrder\u003c/p\u003e \u003cp\u003eProject\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEye\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003cp\u003e(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFAZ\u003c/p\u003e \u003cp\u003e(mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSCP-VD\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eIL\u0026minus;6\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIL\u0026minus;8\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVCAM\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePGF\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eMCP\u0026minus;1\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e686\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37.21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e165.4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e68.2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e123.6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2354.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e65.3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e693.2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e368\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e42.12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e40.3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e18.7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e191\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e104.8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e42.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e639.5\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e79\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e611\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.515\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e38.16\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e248.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e27.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e85.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e157.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e62.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e414.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e672\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.382\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e39.42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e81.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e44.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e68.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e1219.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e67.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e712.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e60\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e812\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.402\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e37.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e213.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e52.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e93.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e1942.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e53.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e852.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e54\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e466\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.483\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e40.18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e332.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e16.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e85.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e920.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e52.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e541.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e73\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e681\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.490\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e37.86\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e93.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e18.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e221.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e53.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e104\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e610.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e65\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e1017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.532\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e38.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e277.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e67.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e452.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e793.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e117.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e682.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e65\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e801\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.458\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e39.42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e247.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e33.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e98.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e1965.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e67.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e586.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e51\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e306\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.412\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e41.68\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e27.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e19.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e48.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e469.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e26.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e612.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e59\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e423\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.371\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e40.23\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e165.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e75.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e51.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e7980\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e97.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e1101.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e54\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e663\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.542\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e39.56\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e90.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e44.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e105.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e5235.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e87.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e772.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e37\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e691\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.475\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e38.71\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e80.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e15.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e57.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e1585.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e65.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e974.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e37\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e395\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.383\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e41.26\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e146.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e17.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e88.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e3817.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e80.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e273.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e58\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e560\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.431\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e40.98\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e52.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e16.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e22.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e642.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e47.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e347.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e16\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e58\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e625\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.387\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e38.42\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e235.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e62.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e123.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e2364.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e67.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e512.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e76\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e310\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.453\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e41.61\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e53.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e56.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e22.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e7911.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e102.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e658.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e52\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eF\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e495\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.379\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e40.95\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e214.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e26.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e39.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e939.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e101.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e516.20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\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=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e478\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.502\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e40.12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e156.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e74.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e142.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e2431.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e153.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e498.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e63\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e396\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.413\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e41.31\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e99.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e16.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e34.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003e652.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e72.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003e356.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eCRVO-ME: center retinalvein occlusive-macular edema; CRT: central retinal thickness; FAZ: foveal avascular area;SCP-VD: superficial capillary plexus-vessel density ; IL: interleukin; VEGF: vascular endothelial growth factor; VCAM: vascular cell adhesion molecule; PGF: placental growth factor; MCP: monocyte chemotactic protein\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn this study, 20 cases of CRVO patients and 20 eyes were selected, with an average age of onset ranging from 35 to 79 years old, with a mean age of 56.55\u0026thinsp;\u0026plusmn;\u0026thinsp;12.00 years. Among them, 11 were male and 9 were female; 7 eyes were in the right eye and 13 in the left eye. All patients had not received vitreous injection or fundus laser therapy before.\u003c/p\u003e\n\u003ch3\u003e2. CRVO-ME patient CRT,FAZ and SCP-VD test results in this study ( Table )\u003c/h3\u003e\n\u003cp\u003eIn this study, the average CRT of 20 eyes of CRVO-ME patients was (572.80\u0026thinsp;\u0026plusmn;\u0026thinsp;186.57) \u0026micro;m; FAZ area was (0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06) mm\u003csup\u003e2\u003c/sup\u003e and SCP-VD was (39.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56)%。\u003c/p\u003e\n\u003ch3\u003e3. Results of aqueous cell factor detection in CRVO-ME patients in this study ( Table )\u003c/h3\u003e\n\u003cp\u003eIn this study, the average concentrations of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in 20 eyes of patients were (151.16\u0026thinsp;\u0026plusmn;\u0026thinsp;88.61) pg/ml, (38.63\u0026thinsp;\u0026plusmn;\u0026thinsp;22.29) pg/ml, (107.72\u0026thinsp;\u0026plusmn;\u0026thinsp;96.76) pg/ml, (2177.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2357.69) pg/ml, (76.53\u0026thinsp;\u0026plusmn;\u0026thinsp;29.48) pg/ml, and (617.69\u0026thinsp;\u0026plusmn;\u0026thinsp;205.87) pg/ml, respectively.\u003c/p\u003e \u003cp\u003e4. Correlation analysis of the concentration of IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 in the aqueous humor of CRVO-ME patients with CRT, FAZ and SCP-VD (Attached Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e to Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study analyzed the concentration of aqueous humor and intraocular fluid variables in 20 eyes from 20 individuals with CRVO-ME, revealing results by Pearson correlation analysis: CRT had a substantial positive correlation with the amounts of aqueous humor cytokines IL-6 and VEGF (r\u0026thinsp;=\u0026thinsp;0.450,0.593, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); however, it showed no correlation with IL-8, MCP-1, PGF, or VCAM (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The area of FAZ exhibited a strong positive correlation with the concentration of VEGF (r\u0026thinsp;=\u0026thinsp;0.489, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); but no correlation was seen with IL-6, IL-8, MCP-1, PGF, or VCAM (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The SCP-VD exhibited a strong negative correlation with IL-6 (r=-0.462, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); however, it showed no correlation with IL-8, VEGF, MCP-1, PGF, or VCAM (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) ( Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation analysis between CRT, FAZ area, SCP-VD and cytokine concentration in aqueous humor of CRVO-ME patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAqueous cell factor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFAZ area\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eSCP -VD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eR\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.365\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.171\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.593\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVCAM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.921\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.322\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.166\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCRVO-ME: retinal center vein occlusive macular edema; CRT: central retinal thickness; SCP: superficial capillary plexus; FAZ: foveal avascular area; IL: interleukin; VEGF: vascular endothelial growth factor; VCAM: vascular cell adhesion molecule; PGF: placental growth factor; MCP: monocyte chemotactic protein\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe exploration of representative imaging biomarkers, the integration of intraocular fluid with fundus imaging biomarkers to evaluate the condition and forecast the prognosis of ME and its underlying diseases, as well as the optimization of treatment strategies, will provide substantial guidance for the management of ME and its associated conditions. Particularly in the initial phases of ME, this thorough evaluation method enhances the understanding of the diseases pathogenesis and facilitates the early identification of refractory ME, thereby providing essential evidence for clinical treatment, forecasting vision recovery, and allowing for personalized precision therapy. This consequently establishes a scientific foundation for the selection of clinical treatment techniques. Early care can significantly decelerate or avert the advancement of ME and its underlying conditions, improve patients visual prognosis, and enhance their quality of life.\u003c/p\u003e \u003cp\u003eTo avoid serious complications that may arise from vitreous puncture and aspiration (such as vitreous incarceration)\u003csup\u003e[15]\u003c/sup\u003e, this study selected anterior chamber aqueous humor from ME patients as the research subject. This study selected CRVO-ME patients, the most prevalent and representative examples of ME, to examine the association between aqueous humor cytokines and imaging biomarkers. Twenty cases (20 eyes) from CRVO-ME patients were selected for testing the concentrations of IL-6, IL-VEGF, VCAM, PGF, and MCP-1. The OCT and OCTA findings were correlated with clinically accessible and quantified fundus imaging results to enhance the precision of ME treatment. This study selects fundus imaging markers selected are CRT, SCP-VD, and FAZ, which possess substantial clinical significance and are readily accessible. Such parameters are periodically measured in the ophthalmology clinics, which makes them convenient biomarkers when it comes to creating disease progression and treatment response.\u003c/p\u003e \u003cp\u003eCRT is a metric employed to objectively evaluate the extent of macular thickening by measuring the vertical distance between the inner limiting membrane of the macular fovea and the retinal pigment epithelium basement membrane in OCT images\u003csup\u003e[16]\u003c/sup\u003e .This metric can objectively and intuitively evaluate the extent of macular thickness, which is essential for the diagnosis and monitoring of ME. The CRT of eyes with CRVO-ME was measured at (572.80\u0026thinsp;\u0026plusmn;\u0026thinsp;186.57) \u0026micro;m, which is much greater than the normal upper limit of 250 \u0026micro;m, indicating considerable macular thickening in individuals. Nonetheless, we discovered that CRVO-ME patients with SRD, despite exhibiting increased central macular thickness (CMT) and foveal choroidal thickness (SFCT), presented with reduced central retinal thickness (CRT). Consequently, investigating the link between CRT and intraocular fluid may provide inaccuracies in research with limited sample sizes.\u003c/p\u003e \u003cp\u003eThe central fovea of the macula is the most sensitive region of vision, characterized by a few hundred microns of avascular tissue in its core. This area is called the macula central Fovea avascular zone (FAZ)\u003csup\u003e[17]\u003c/sup\u003e .The dimensions of FAZ are directly correlated with visual prognosis. The occurrence of lesions significantly impacts central vision and visual acuity. Damage to retinal microcirculation and capillary ischemia in RVO result in the enlargement of FAZ area. Simultaneously, it was determined that FAZ has heightened sensitivity to variations in blood flow and can indicate the condition of retinal capillaries\u003csup\u003e[18]\u003c/sup\u003e .A substantial quantity of samples indicated that in patients, eyes with an enlarged FAZ region exhibited diminished vision, and a significant negative association existed between FAZ area and visual acuity \u003csup\u003e[19]\u003c/sup\u003e .The FAZ area in the affected eyes of this cohort with CRVO-ME it was (0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06) mm\u0026sup2;, greatly beyond the normal range (0.25\u0026thinsp;~\u0026thinsp;0.30) mm\u0026sup2;. Nevertheless, the FAZ region is intricately linked to axial length and ocular growth, rendering it very imprecise when utilized as a solitary variable for quantitative assessment. However, enlarging the FAZ continues to be a potent predictor of visual poor prognosis and needs to be incorporated with the rest of the imaging biomarkers.\u003c/p\u003e \u003cp\u003eThe retinal superficial capillary plexus-vessel density (SCP-VD) is defined as the ratio of vessels to the entire measured area, indicating retinal blood flow perfusion\u003csup\u003e[20]\u003c/sup\u003e .Lee\u003csup\u003e[21]\u003c/sup\u003eStudies have found that the integrity of the peripapillary choroidal plexus (DCP) is closely associated with the effectiveness of anti-VEGF medications in the treatment of ME. The extent of DCP loss may serve as a significant predictive marker for the likelihood of a successful response to anti-VEGF therapy. It has been proven that in eyes with DME, there exists a substantial negative association between SCP vascular density and visual acuity. In cases of moderate to severe CRVO, the presence of retinal edema, vitreous opacity, and vitreous hemorrhage considerably skews the quantitative data of deep DCP vascular density, complicating accurate measurement. Consequently, this study designated SCP as the subject of investigation. In this group, the SCP blood flow density in eyes with CRVO-ME was (39.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56)% lower than in normal eyes, indicating that the damage to SCP in ME eyes is more severe.\u003c/p\u003e \u003cp\u003eMoreover, the high reflectivity point (hyperreflective dots, HRD) on OCT appears as discrete high reflectivity particles with a diameter of 20\u0026ndash;30\u0026micro;m in OCT. It is presently thought that it emanates from inflammatory activated microglia\u003csup\u003e[22]\u003c/sup\u003e. Prior research has established that microglia reside in the inner layer of retina as an innate immune cell, which get activated with retinal injury. Certain microglia will migrate to the outer retinal layer and aggregate to contribute to the synthesis of pro-inflammatory cytokines\u003csup\u003e[23]\u003c/sup\u003e .HRD was linked to the integrity of light receptors on OCT and visual prognosis\u003csup\u003e[24]\u003c/sup\u003e .Recently, Professor Yao Jin\u0026rsquo;s team in China discovered a substantial correlation between the elevation of inflammatory components and the quantity of HRD through the analysis of several cases .Moon\u003csup\u003e[25]\u003c/sup\u003e demonstrated that eyes with SND exhibited increased IL-6 levels, signifying active inflammation, and that eyes with SND coupled with DME responded significantly to dexamethasone implants, supporting the utilization of dexamethasone implants in patients with SND .In the future, other biological indicators will be investigated for diagnosing patients and assessing the course of intraocular diseases.\u003c/p\u003e \u003cp\u003eAmong the cytokines in the eye, six representative cytokines IL-6, IL-8, VEGF, VCAM, PGF and MCP-1 were selected to obtain rapid test results by flow cytometer.\u003c/p\u003e \u003cp\u003eIL-6, as a representative of inflammatory factors, is pivotal in expediting the inflammatory response, enhancing vascular permeability, producing vascular leakage, and stimulating other cytokines (such as VEGF factor and ICAM-1 factor)\u003csup\u003e[26]\u003c/sup\u003e.IL-6 serves as a catalyst for inflammatory responses by facilitating immunological reactions, chiefly through the promotion of B cell development and antibody synthesis, alongside the induction of T cell activation, proliferation, and differentiation. IL-6 enhances endothelial cell permeability and vascular leakage by suppressing the expression of tight junction proteins occludin and ZO-1, hence widening the intercellular gaps \u003csup\u003e[27]\u003c/sup\u003e .Glucocorticoids (such as dexamethasone implant) improve refractory ME by inhibiting inflammatory factors such as IL-6 and TNF-α. Research indicates that the combination of anti-VEGF and subfascial sac hormone therapy can synergistically diminish aqueous levels of VEGF and IL-6, hence enhancing efficacy\u003csup\u003e[28]\u003c/sup\u003e. This study found a positive association between IL-6 and CRT, and a negatively correlated between IL-6 and SCP-VD in patients with CRVO-ME, indicating that IL-6 may be a contributing factor to the progression of CRVO-ME and is significantly associated with vascular damage. This result confirms the relevance of targeting the VEGF as well as IL-6 pathways, which could be achieved with the help of anti-VEGF therapy combining with corticosteroids.\u003c/p\u003e \u003cp\u003eIL-8, a prevalent chemotaxis, can induce the chemotaxis of neutrophils, T lymphocytes and eosinophils, signifying the presence of intraocular inflammation\u003csup\u003e[29]\u003c/sup\u003e. During prolonged ischemia and hypoxia in the eye, IL-8 is generated to inhibit neutrophils and T cells, exhibiting a favorable correlation with VEGF levels, which together facilitate the onset and progression of ME. Yoshida et al\u003csup\u003e[30]\u003c/sup\u003e Using control experiments, it was found that the level of IL-8 in the vitreous body of patients with retinal neovascularization is significantly elevated. In retinas exhibiting neovascularization has occurred, immunostaining for IL-8 was observed in vascular endothelial cells and glial cells, indicating that IL-8 plays a role in neovascularization. Wu F et al\u003csup\u003e[31]\u003c/sup\u003eIn individuals with macular edema, notable elevations in IL-8 levels were detected in the vitreous and aqueous humor, and these IL-8 levels associated with the severity of macular edema and the extent of glial cell obstruction in retinal arteries. This study found that IL-8 concentrations did not exhibit significant relationships with CRT, FAZ area, or SCP blood flow density, suggesting a minimal impact.\u003c/p\u003e \u003cp\u003eVEGF is the cytokine most intimately associated with the onset of macular edema, which alters the cellular microenvironment, enhances vascular permeability, facilitates the migration and proliferation of vascular endothelial cells, and induces angiogenesis \u003csup\u003e[32]\u003c/sup\u003e .Its concentration indicates the extent of neovascularization in the eye and is presently the most potent angiogenic factor identified. This investigation revealed that in CRVO, both CRT and FAZ areas had a strong positive correlation with VEGF content in the aqueous humor, underscoring the pivotal role of VEGF in the pathophysiology of macular edema. This outcome corroborates the efficacy of anti-VEGF agents as a primary treatment for CRVO-ME, hence reinforcing the significance of VEGF as a therapeutic target.\u003c/p\u003e \u003cp\u003eVCAM, a cell adhesion molecule, is linked to the rupture of blood eye barrier, and elevated titers signify the existence of intraocular tissue edema\u003csup\u003e[33]\u003c/sup\u003e. It is a sign of vascular endothelial activation injury and is crucial for the adherence of inflammatory cells. It is frequently excessively heightened in chronic inflammation\u003csup\u003e[34]\u003c/sup\u003e. In this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area or SCP blood flow density, suggesting it had no substantial impact on RVO.\u003c/p\u003e \u003cp\u003ePGF can stimulate endothelial cell proliferation and migration, anti-endothelial cell apoptosis, increase vascular permeability, enhance the biological activity of low concentration of VEGF, is an important angiogenic factor involved in the angiogenesis of various malignancies \u003csup\u003e[35]\u003c/sup\u003e. In this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area, or SCP blood flow density, suggesting that its impact on CRVO was negligible.\u003c/p\u003e \u003cp\u003eMCP-1, a significant pro-inflammatory agent within the chemokine family, contributes to the course of CRVO by mediating inflammation, facilitating the chemotaxis of lymphocytes and monocytes, activating signaling pathways, and promoting angiogenesis \u003csup\u003e[36]\u003c/sup\u003e. MCP-1 attracts chemotactic inflammatory cells, including monocytes and macrophages to accumulate in the retinal capillaries. The narrow width of the capillaries predisposes them to obstruction, while elevated hydrostatic pressure results in vascular leakage and the development of retinal aneurysms, hence exacerbating the evolution of ME from numerous perspectives \u003csup\u003e[37]\u003c/sup\u003e. However, in this investigation, its concentration did not exhibit a significant correlation with CRT, FAZ area or SCP blood flow density, suggesting it had no substantial impact on CRVO.\u003c/p\u003e \u003cp\u003eThe findings of this study demonstrate that in ME pathophysiology, the expression of local and systemic inflammatory factors and chemokines is markedly elevated, instigating widespread inflammatory responses. This inflammatory response results in damage to retinal microvessels and structures, undermines the primary immune defense in the retina, the BRB, and further intensifies the cycle of macular edema while facilitating the development of aberrant neovascularization \u003csup\u003e[38]\u003c/sup\u003e. The findings of this study are mostly aligned with the experimental studies conducted internationally \u003csup\u003e[36]\u003c/sup\u003e .The relationship between detection outcomes and readily obtainable, measurable fundus imaging data can be elucidated from many perspectives, offering guidance for the targeted therapy of ME.\u003c/p\u003e \u003cp\u003eThe aging process is progressively intensifying, hence exacerbating the prevalence of CRVO-ME. The deterioration of patients' vision significantly diminishes their quality of life and impairs the stable and healthy progression of social economy. Efforts have been undertaken both domestically and internationally to investigate the optimal treatment for ME. The prevalence of patients with refractory macular edema is rising. Within 2 years of receiving monthly anti-VEGF treatments, the probability of refractory ME can reach nearly 40%. Nonetheless, the majority of patients with resistant macular edema have attained significant therapeutic outcomes with the substitution of various anti-VEGF agents, intravitreal injections of hormones, peripapillary micro-photocoagulation, vitrectomy+ endophakic extraction. Patients will gain greater advantages from the accurate diagnosis of refractory macular edema by the utilization of biological markers in imaging, resulting in early vision enhancement. Prompt identification of these individuals via imaging and the prompt implementation of targeted therapy can optimize the avoidance of additional visual deterioration.\u003c/p\u003e \u003cp\u003eAnti-VEGF pharmacotherapy has been clinically substantiated for the treatment of conditions such as RVO. RVO has a definitive efficacy in enhancing vision and markedly surpasses conventional retinal laser photocoagulation in alleviating macular edema. The medication results in fewer adverse events; initiating it earlier improves long-term visual prognosis and reduces the duration of treatment necessary. Nonetheless, a significant proportion of resistant patients with edema continue to have a delayed or no response to anti-VEGF medications. Corticosteroids have been demonstrated to be particularly beneficial in the treatment ME and are now extensively utilized for the anti-inflammatory management of ocular diseases. In the current era of prevalent intravitreal injections of anti-VEGF and anti-inflammatory agents, monoclonal antibodies, bispecific antibodies, fusion proteins, small molecule antibodies, and single-chain antibody fragment therapeutics are progressively appearing. \u0026zwnj;Aflibercept exhibits multiple mechanisms of action, targeting both anti-VEGF and anti-PLGF pathways \u003csup\u003e[39]\u003c/sup\u003e. Simultaneously, Faricimab has dual effects of anti-VEGF and anti-Ang-2\u003csup\u003e[40]\u003c/sup\u003e. Bevacizumab is a complete VEGF-A inhibitor, characterized by its molecular weight of 26kDa and significant tissue penetration, which enhances its efficacy in eliminating IRF and SRF\u003csup\u003e[41]\u003c/sup\u003e. Aodi, as a sustained-release agent of dexamethasone, can enhance the inflammatory response in the vitreous cavity and sustain its impact for 3\u0026ndash;6 months\u003csup\u003e[42]\u003c/sup\u003e. Consequently, a varied array of therapeutic agents and protocols provides patients with increased alternatives while posing new obstacles for clinicians in their diagnostic and therapeutic decisions. Investigating accurate ME diagnosis and treatment strategies entails utilizing fundus imaging markers to deduce the therapeutic activity within the patient's eye, selecting optimal medications to enhance vision, identifying more efficacious treatments, augmenting diagnostic precision, and improving patient outcomes.\u003c/p\u003e \u003cp\u003eThis study possesses some limitations: (1) The participants discussed in this paper were examined prior to intravitreal medication injection therapy. Phase II clinical trials are presently undertaking long-term follow-ups on patients, incorporating multicenter, large-sample investigations, prolonging the observation time, and integrating more detailed and comprehensive imaging indicators for correlation analysis, including DRIL, IRC, and SRF. The correlation between these disorders will be assessed, and a predictive model for macular edema lesions will be developed. Measures will be undertaken to integrate many elements, increase vigilance, and swiftly execute actions to avert or postpone advancement, thus facilitating early prevention and management of the disease. (2) Due to extensive data from both domestic and international sources indicating that RVO patients have higher levels of aqueous humour cytokine compared to normal eyes\u003csup\u003e[43]\u003c/sup\u003e. There is an agreement both domestically and internationally that the alterations in the fundus imaging of patients markedly differ from the quantitative analysis of normal eyes\u003csup\u003e[2,16,44]\u003c/sup\u003e. This study attempts to evaluate the association between the two, hence, a healthy control group was not included in this study. Our study team is presently performing a correlation analysis between intraocular fluids, specifically DME and AMD and imaging biomarkers, which will be subsequently compared and discussed. (3) In our study, the correlation analysis between cytokines and imaging biomarkers was conducted using univariate correlation analysis. During the development and treatment of ME, a vast array of molecular pathways is implicated, and multivariate and multifactorial correlation analysis is anticipated to yield more substantial evidence of relationship.\u003c/p\u003e \u003cp\u003eImaging-based biological markers, in conjunction with intraocular fluid analysis, can substantially aid in directing treatment and forecasting results for ME patients, enhancing management strategies and increasing patient adherence to treatment protocols. Integrating OCT, OCTA, and intraocular cytokine analysis, artificial intelligence analyzes fundus imaging images to automatically correlate cytokine profiles, achieving precise typing. Predictive models are developed by integrating many characteristics to facilitate early prevention and prompt intervention, therefore averting or postponing the advancement of ME and its associated disorders. Fundus imaging investigations of macular edema and intraocular cytokine analysis yield essential insights into their etiology and enhance treatment strategies. The integration of dynamic imaging monitoring with molecular biology approaches offers potential for individualized therapy and enhanced patient outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e(1)Cytokine expression was associated with the macular structure of the macula and the extent of microvascular damage surrounding the macula.\u003c/p\u003e \u003cp\u003e(2)The biological indicators could improve therapy decision-making and precision medicine.\u003c/p\u003e \u003cp\u003e(3)Future management of CRVO-ME should encompass not just anti-VEGF medication but also targeted anti-inflammatory agents, and additional therapeutic modalities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eDisclosure statement\u003c/p\u003e\n\u003cp\u003eNo potential conflict of interest was reported by the author(s).\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the authors.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis project is not funded by any grant.\u003c/p\u003e\n\u003cp\u003eEthics declarations\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. Ethical approval was reviewed by Linyi People\u0026apos;s Hospital. All of the participants signed informed consent forms.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJie Gao, Tao Wangprimarily responsible for literature retrieval, data processing, and article writing.Huiwen Pang was responsible for reviewing statistical.Maojuan Feng,Weijie Zhang were responsible for editing and reviewing the articles.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDaruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, Rothschild PR, Omri S, G\u0026eacute;liz\u0026eacute; E, Jonet L, Delaunay K, De Kozak Y, Berdugo M, Zhao M, Crisanti P, Behar-Cohen F. Mechanisms of macular edema: Beyond the surface. Prog Retin Eye Res. 2018 Mar;63:20-68. doi: 10.1016/j.preteyeres.2017.10.006. Epub 2017 Nov 7. 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J Diabetes Res. 2018 Apr 4;2018:8546423. doi: 10.1155/2018/8546423.\u003c/li\u003e\n\u003cli\u003eMunk MR, Ceklic L, Stillenmunkes R, Chaudhary V, Waheed N, Chhablani J, de Smet MD, Tillmann A. Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies. Diagnostics (Basel). 2024 Sep 7;14(17):1983. doi: 10.3390/diagnostics14171983. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Macular edema, Central retinal vein occlusion, humour cytokine, Biological markers, Ophthalmology","lastPublishedDoi":"10.21203/rs.3.rs-9449389/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9449389/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aims to examine the relationship between the concentrations of different aqueous humour cytokine and the Central retinal thickness (CRT), the area of the Foveal avascular zone (FAZ)and the vascular density of superficial capillary plexus (SCP-VD) in patients with Central Retinal Vein Occlusion-Macular Edema ༈CRVO-ME༉ through a prospective clinical investigation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 20 cases with 20 eyes were included from Linyi Peoples Hospital. OCT and OCTA were employed to examine a 6 mm \u0026times; 6 mm region in the macula, acquiring CRT, FAZ area, and SCP-VD data. Aqueous humor samples were collected to measure its Interleukin-6(IL-6),Interleukin-8 ( IL-8),Vascular endothelial growth factor (VEGF༉, Vascular cell adhesion molecule (VCAM༉, Placental growth factor ( PGF༉, and Monocyte chemoattractant protein-1 (MCP-1༉ level. The correlation between these values of CRT, FAZ area, and SCP-VD in the affected eye were analyzed using statistical Pearson methods.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe CRT of the affected eye in CRVO-ME patients was (572.80\u0026thinsp;\u0026plusmn;\u0026thinsp;186.57) \u0026micro;m; the SCP-VD was (39.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56) %; and the FAZ area was (0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06) mm\u0026sup2;. The concentrations of IL-6, IL-8, VEGF, VCAM, PGF, and MCP-1 in CRVO-ME patients were (151.16\u0026thinsp;\u0026plusmn;\u0026thinsp;88.61), (38.63\u0026thinsp;\u0026plusmn;\u0026thinsp;22.29), (107.72\u0026thinsp;\u0026plusmn;\u0026thinsp;96.76), (2177.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2357.69), (76.53\u0026thinsp;\u0026plusmn;\u0026thinsp;29.48), and (617.69\u0026thinsp;\u0026plusmn;\u0026thinsp;205.87) pg/ml, respectively. Correlation analysis showed that CRT was significantly positively correlated with the IL-6 and VEGF concentrations (r\u0026thinsp;=\u0026thinsp;0.450,0.593, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); FAZ area was significantly positively correlated with VEGF (r\u0026thinsp;=\u0026thinsp;0.489, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); and SCP-VD was significantly negatively correlated with IL-6 (r = -0.462, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe concentration of intraocular cytokines exhibited a substantial correlation with the macular structure of the macula and the extent of microvascular damage surrounding the macula.\u003c/p\u003e","manuscriptTitle":"Correlation between aqueous humour cytokine and Imaging Biomarker in CRVO-ME","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 08:28:54","doi":"10.21203/rs.3.rs-9449389/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"206536385049890452356627144860441568070","date":"2026-05-05T16:16:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-30T04:51:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-30T04:47:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-29T04:37:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-28T17:28:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-04-28T15:19:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ab7c7008-3cbc-4793-ba85-d87b90a4870e","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"206536385049890452356627144860441568070","date":"2026-05-05T16:16:01+00:00","index":45,"fulltext":""},{"type":"reviewersInvited","content":"16","date":"2026-04-30T04:51:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-30T04:47:51+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T08:28:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 08:28:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9449389","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9449389","identity":"rs-9449389","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}