Quantitative data analysis of optical coherence tomography angiography of different morphologies of macular neovascularization after intravitreal conbercept versus ranibizumab for neovascular age-related macular degeneration

Quantitative data analysis of optical coherence tomography angiography of different morphologies of macular neovascularization after intravitreal conbercept versus ranibizumab for neovascular age-related macular degeneration | 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 Quantitative data analysis of optical coherence tomography angiography of different morphologies of macular neovascularization after intravitreal conbercept versus ranibizumab for neovascular age-related macular degeneration Jing Li, Zhufang Yang, Xueying Li, Di Li, Jin Yang, Meijia Dang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2326056/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose We sought to analyze quantitative data findings of optical coherence tomography angiography (OCTA) of different morphologies of macular neovascularization (MNV) in patients with neovascular age-related macular degeneration (nAMD) who received intravitreal conbercept (IVC) or ranibizumab (IVR). Methods This was a prospective, interventional case series study and involved 39 patients, including 23 treated with 0.05 mL of conbercept and 16 treated with 0.05 mL of ranibizumab. Patients with MNV were diagnosed with nAMD for the first time at Shaanxi People's Hospital and all were treated with the "3 + PRN" regimen. These MNV cases could be further divided into four OCTA patterns: the “Medusa” pattern, the “tangled” pattern, the “seafan” pattern, and the “other” pattern. Patients were examined using OCTA before (T1) the injection and at 1 day (T2), 7 days (T3), 30 days (T4), 60 days (T5), and 90 days (T6) after anti–vascular endothelial growth factor (VEGF) treatments. Main outcome measures included best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density ratio (MNV-VD ratio), and central macular thickness (CMT). Results Forty-four eyes of 39 patients with nAMD (17 men and 22 women) were included. The average age of participants was 71.34 ± 10.34 years (range, 50–91 years). Twenty-eight eyes (23 patients) received IVC, and 18 eyes (16 patients) received IVR. At 90 days after treatment, the mean BCVAs of patients with the four patterns in the IVC group were improved ( P = 0.002); notably, the tangled pattern patients had significantly better results than those with the other three patterns ( P = 0.007). Eyes with all four patterns showed significant CMT decreases from the baseline level at 90 days, but there was no significant difference in the total change of CMT between the eyes with different patterns ( P = 0.052). The mean MNV-VA and MNV-VD ratios were reduced in all four pattern groups, although the difference of the Medusa pattern was statistically significant for the mean MNV-VA ( P = 0.008) but not the mean MNV-VD ratio ( P = 0.107). In the IVR group, among the four patterns, the patients with the seafan MNV pattern showed a more significant BCVA improvement ( P = 0.042). The mean CMTs of four MNV patterns were decreased after treatment, most notably in patients with the other pattern, but there was no significant difference ( P = 0.114). Considering MNV parameters, the mean MNV-VA of the seafan pattern and the mean MNV-VD of the other pattern were significantly decreased, albeit without significant differences ( P = 0.225 and P = 0.109). For the comparison between the 2 groups, the mean BCVA, CMT, and MNV parameters were all not significantly different between pre-injection and at the last visit (90 days) after injection. Conclusions The distinct morphologies of MNV in nAMD patients can be identified and quantitatively analyzed by OCTA. These different patterns might be useful and instructive predictors for the prognosis of nAMD patients after anti-VEGF therapy. Conbercept for patients with the tangled MNV pattern and ranibizumab for patients with the seafan MNV pattern may be considered as therapeutics. Trial registration number ChiCTR2200056961 Macular neovascularization (MNV) Neovascular Age-related Macular Degeneration(nAMD) Morphological anti Vascular Endothelial Growth Factor (VEGF) Optical Coherence Tomography Angiography (OCTA) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Neovascular age-related macular degeneration (nAMD), also known as exudative AMD, is caused by damage to Bruch’s membrane, and pathological neovascularization progresses to the retinal pigment epithelium (RPE) and neurosensory retina through Bruch’s membrane damage, resulting in macular neovascularization (MNV). Owing to the abnormal structure of neovascularization, the formation of MNV will cause a series of pathological processes, such as exudation, bleeding, organization, and fibrotic scarring, resulting in the loss of central vision [ 1 , 2 ]. Anti–vascular endothelial growth factor (anti-VEGF) treatment has become the most important and effective therapeutic method for nAMD in clinic. Its effect stems from the finding that VEGF is the key cytokine related to ocular neovascularization [ 3 – 5 ]. First-line intravitreal-injectable anti-VEGF drugs for the treatment of nAMD include ranibizumab (Genentech, Inc. and Novartis International AG, Basel, Switzerland), which is a representative of monoclonal antibodies, and aflibercept (Regeneron Pharmaceuticals Inc., Bayer Healthcare Company Limited, Leverkusen, Germany) and conbercept (KH902) (Lumitin; Chengdu Kanghong Biotech, Ltd., Sichuan, China), which are both soluble fusion protein agents [ 6 ]. For most nAMD patients, anti-VEGF drugs can effectively inhibit the leakage and bleeding of MNV; however, the responses of nAMD patients with MNV to anti-VEGF therapy are heterogeneous, suggesting that the pathological basis for this condition is multifactorial in nature. The diagnosis of MNV is generally made using fluorescein angiography (FA) or indocyanine green angiography (ICGA), which can dynamically display the abnormal vessels and observed vascular leakage. Optical coherence tomography (OCT) angiography (OCTA) with a high sensitivity of detection of MNV in nAMD—as a fast, safe, non-invasive, and repeatable imaging modality able to better illustrate the microvasculature of retina and choroid—could realize a detailed visualization of different types of MNV [7.8]. Quantitative information regarding MNV flow and area can also been detected and obtained [ 9 ]. Several studies had described the morphological features and classified the “tangled” or “glomerulus” and “seafan” or “Medusa” types of MNV in nAMD using OCTA [10.11]. Investigators have assessed the evolution of OCTA qualitative and quantitative biomarkers, including branching capillaries, anastomoses and loops, peripheral arcade, and hypointense halo for MNV after anti-VEGF therapy in recent years [ 12 , 13 ]. Nevertheless, the variations in and clinical implications of OCTA quantitative data of different morphological patterns of MNV after anti-VEGF treatment remain unknown. Furthermore, as is known, the structure and mechanism differ between conbercept and ranibizumab, and no study has reported the OCTA quantitative outcomes of different morphological patterns MNV for nAMD treated with intravitreal injection of conbercept (IVC) compared to ranibizumab. In addition, the relationship between these OCTA quantitative parameters and visual prognosis after different anti-VEGF drug treatments remains under evaluation and inconclusive. The current study sought to analyze the quantitative parameters outcomes identified with OCTA examination after a “3 + PRN” regimen of IVC or IVR in patients with different morphological patterns of MNV and compare the visual prognosis of different MNV morphologies after IVC or IVR treatment. To the best of our knowledge, this is the first study to evaluate quantitative parameters changes among the different MNV patterns identified by OCTA for nAMD patients treated with conbercept. 2. Materials And Methods 2.1 Study Design This prospective, interventional case series study was conducted at Shaanxi Provincial People’s Hospital (Xi’an, China). The study was approved by the ethics committee of Shaanxi Provincial People’s Hospital (Xi’an, China) in accordance with the Declaration of Helsinki. Written informed consent was obtained from each study subject before the intravitreal injection of anti-VEGF agents was performed.we had access to information that could identify individual participants during or after data collection. 2.2 Study Subjects This study recruited 39 patients with nAMD who were given an intravitreal injection of ranibizumab or conbercept at Shaanxi Provincial People’s Hospital between April 2020 and August 2021. Only patients who had not previously received any treatment for nAMD were enrolled; in other words, all participants enrolled in the present study were treatment-naive. The inclusion criteria for the patients with nAMD were as follows: (1) Age ≥ 50 years; (2) OCT/OCTA showed intra/subretinal fluid (IRF/SRF) or retinal pigment epithelium detachment (PED); (3) MNV was defined by FA, ICGA, and OCTA; and (4) the patient relatively clearly showed either the "Medusa," " seafan," or "tangled" type of MNV. The exclusion criteria for this study were as follows: (1) systemic and ocular diseases that cause changes in fundus vasculopathy (e.g., diabetic retinopathy, retinal vascular obstruction); (2) another ocular maculopathy causing MNV (e.g., polypoidal choroidal vasculopathy, myopic maculopathy, central serous chorioretinopathy, macular telangiectasia); (3) the refractive stroma was obviously turbid and cannot cooperate with the examination; and (4) a history of previous eye surgery or therapy except cataract (e.g., vitrectomy, photodynamic therapy, other drug injection). 2.3 Treatment Twenty-six eyes of 23 patients received treatment with conbercept (0.5 mg/0.05 mL) and 18 eyes of 16 patients were treated with ranibizumab (0.5 mg/0.05 mL). The procedure of intravitreal injection was performed by the same retina specialist (J. L.). The treatment protocols followed the "3 + PRN" regimen. All intravitreal injections were strict aseptic operations performed after topical administration using povidone–iodine. The topical antibiotic levofloxacin was given 3 days before or after injection. All of the patients underwent preoperative and postoperative comprehensive ophthalmologic examinations, including slit-lamp biomicroscopy and dilated fundus examination. 2.4 Data Collection, Image Acquisition, and Analysis The baseline characteristics of all enrolled patients, such as age, gender, and past history, were recorded. The best-corrected visual acuity (BCVA) was measured and recorded by the same clinician and converted according to the minimum resolution angle logarithm (logMAR) visual acuity. We used a 512 × 128 scanning mode to measure the central macular thickness (CMT) (internal limiting membrane [ILM] to RPE distance) [ 14 ]. Using depth enhancement, the artifact removal model was used to track the retina of the same level of the deep macular 6 × 6 mm 2 region until 2 scans of good quality were obtained. The OCT-based optical microangiography (OMAG) algorithm can detect the amplitude and phase changes between continuous B-scans at the same position, quantify the motion contrast, and generate the OCTA image [ 15 ]. Using the built-in OCTA software to manually divide the RPE layer to extract the lesser profile image, we analyzed and recorded the RPE–RPE fit level using OCTA, manually fine-tuned the boundary line to display the clearest MNV morphology and record the value section, and ensured that six images were acquired at the same RPE level to reduce errors. First, we saved the images in a unified format and then imported into the ImageJ software (U.S. National Institutes of Health, Bethesda, MD, USA) to threshold and binarize the pixel intensity. Then, we enlarged each image 800 times, and measured the area of MNV blood vessels by manually sketching the visible blood vessels with a line 1 pixel wide. The vascular density ratio was defined as the ratio of the total pixel area of 6 × 6 mm 2 scanned area occupied by vessels in red pixels. The scale conversion relationship was 68.8335 (PX) = 1 mm. All included patients with neovascular AMD and MNV were exactly examined and diagnosed by the same retina specialist (J. L.) for OCTA examination (CIRRUS HD-OCT model 5000 with AngioPlex®; Carl Zeiss Meditec, Jena, Germany). The baseline and structural data collected before the injection (T1) and at 1 day (T2), 7 days (T3), 30 days (T4), 60 days (T5), and 90 days (T6) after anti-VEGF treatment were collected and analyzed. The BCVA, MNV vascular area (MNV-VA), MNV vascular density ratio (MNV-VD ratio), and (CMT) were compared between before and after treatment. Morphological patterns of the MNV complex on OCTA were studied and classified into four groups, as follows: 1) the “Medusa” pattern, defined as a lesion with branching vessels radiating in all direction from the main vessel trunk at the center; 2) the “seafan” pattern, defined as a lesion with branching vessels radiating from one side of the main vessel trunk; 3) the “tangled” pattern, defined as a lesion with globular structures of entwined vessels without a main vessel trunk [ 16 ]; and 4) the “other” pattern, defined as a lesion with an irregular vessel that can't be attributed to the above three forms but can still be measured. 2.5 Statistical Analysis All statistical analyses were performed using SPSS 26.0 (IBM Corporation, Armonk, NY, USA). Non-parametric statistical methods were used: the Wilcoxon signed-rank test was used to compare the variables of within group differences of different morphology groups before and after treatment, whereas Fisher’s exact test was used for categorical variables and Friedman’s test was used for continuous variables. We used backward elimination of generalized estimating equation (GEE) modeling to evaluate differences between the four OCTA pattern groups after baseline correction. Confidence intervals (CIs) were also calculated using GEE modeling. The model included the time that had elapsed since enrollment, treatment assignment, and interaction between time and treatment. A 2-sided P value < 0.05 was considered statistically significant. 3. Results 3.1 Participant Baseline Characteristics The baseline characteristics of the study participants are listed in Table 1. No age or gender differences were found between the IVC treatment group and IVR treatment group. Thirty-nine nAMD patients, including 17 men and 22 women, with 44 eyes of interest with MNV were included for analysis in this study, stratified as 26 eyes of 23 patients in the IVC group and 18 eyes of 16 patients in the IVR group. The median age of IVC group patients was 61 (range, 50–83) years, and 13 were male and 10 were female. The mean baseline BCVA, CMT, MNV-VA, and MNV-VD ratio values were 0.97 ± 0.50 logMAR, 293.71 ± 145.60 mm, 1.34 ± 1.14 mm 2 , and 0.40 ± 0.10. Of the 26 eyes that showed a distinct MNV complex on OCTA, the Medusa, seafan, tangled, and other patterns were detected in 9 eyes (34.6%), 9 eyes (34.6%), 5 eyes (19.2%), and 3 eyes (11.5%), respectively. The IVR group included 4 men and 12 women with a mean age of 71.61 ± 11.05 (range, 51–91) years; their mean baseline BCVA, CMT, MNV-VA, and MNV-VD ratio values was 0.94 ± 0.54 logMAR, 328.72 ± 144.80 mm, 0.87 ± 0.71 mm 2 , and 0.39 ± 0.06. Of the 18 eyes with MNV in this group, the Medusa, seafan, tangled, and other patterns were detected in 3 eyes (16.7%), 7 eyes (38.9%), 5 eyes (27.8%), and 3 eyes (16.7%). All enrolled patients were observed for 3 months, and no ocular or systemic adverse events were recorded. 3.2 Comparisons of Outcomes in the IVC Treatment Group Twenty-six eyes of 23 patients received primary IVC treatment. At 90 days after treatment, the mean BCVA had improved in the overall cohort from 0.97 ± 0.50 logMAR at baseline to 0.78 ± 0.53 logMAR at the last visit ( P = 0.004). Reductions in the mean CMT (from 293.71 ± 145.60 µm to 211.94 ± 51.11 µm, P = 0.007), the mean MNV-VA (from 1.34 ± 1.14 mm 2 to 0.79 ± 0.59 mm 2 , P = 0.001), and the mean MNV-VD ratio (from 0.40 ± 0.10 to 0.34 ± 0.12, P = 0.037) were noticed after treatment compared to baseline. The mean BCVA of tangled pattern eyes improved from 0.86 ± 0.60 logMAR at baseline to 0.41 ± 0.38 logMAR at the last visit ( P = 0.002), and the degree of BCVA improvement was also significantly higher for patients with the tangled pattern than those with the other three patterns. Specifically, the change associated with the tangled pattern was − 0.43 ± 0.13 (95% CI, − 0.7 to − 0.17; P = 0.001) compared to that of the Medusa pattern group, − 0.30 ± 0.13 (95% CI, − 0.57 to − 0.04; P = 0.023), compared to that of the seafan pattern group, and − 0.34 ± 0.13 (95% CI, − 0.61 to − 0.08; P = 0.01) compared to that of the other pattern group, respectively. The mean CMTs of the four MNV patterns were all decreased after treatment, including most notably in patients with the other pattern, but there was no significant difference in the total change of CMT between the different pattern groups ( P = 0.052). Considering MNV parameters, the Medusa pattern eyes showed a significant reduction in mean MNV-VA after treatment at the last visit (from 2.18 ± 1.36 mm 2 to 0.92 ± 0.74 mm 2 , P = 0.008). The comparison of the change degree of the four MNV patterns showed that the change in the Medusa pattern group was − 1.04 ± 0.40 mm 2 (95% CI, − 1.82 to − 0.27; P = 0.008) compared to that of the tangled pattern group, − 1.03 ± 0.50 mm 2 (95% CI, − 2 to − 0.05; P = 0.038) compared to that of the seafan pattern group, and − 1.25 ± 0.41 mm 2 (95% CI, − 2.05 to − 0.45; P = 0.002) compared to that of the other pattern group, respectively. Therefore, the mean MNV-VA of patients with the Medusa pattern in the IVC group decreased the most. The mean MNV-VD ratios of the four MNV patterns were all decreased at the last visit after treatment compared to baseline, most notably in the Medusa pattern group; however, the changes of all MNV patterns were not significant ( P = 0.107). The comparison of changes in BCVA and CMT between before and after conbercept treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig. 1 and Table 2. The comparison of variation in MNV parameters between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig. 2 and Table 3. An example case of a patient with tangled pattern MNV is shown in Fig. 3 . 3.3 Comparisons of Outcomes in the IVR Treatment Group Eighteen eyes of 16 patients received primary IVR treatment. At 90 days after treatment, the mean BCVA had improved in the overall cohort from 0.94 ± 0.54 logMAR at baseline to 0.70 ± 0.47 logMAR at the last visit ( P = 0.014). Reductions in the mean CMT (from 328.72 ± 144.80 µm to 200.51 ± 90.29 µm, P = 0.001), the mean MNV-VA (from 0.87 ± 0.71 mm 2 to 0.47 ± 0.35 mm 2 , P = 0.133), and the mean MNV-VD ratio (from 0.39 ± 0.06 to 0.31 ± 0.11, P = 0.05) were also noticed. The mean BCVA improvement and CMT decrease between before and after treatment in the overall cohort were statistically significant, while the changes in the mean MNV-VA and MNV-VD ratio were not. The mean BCVA of seafan pattern eyes improved from 0.94 ± 0.40 logMAR at baseline to 0.50 ± 0.32 logMAR at the last visit ( P = 0.042), and the change in BCVA improvement was also significantly greater for the seafan pattern than the other three patterns; specifically, the change in the seafan pattern group was − 0.48 ± 0.10 (95% CI, − 0.69 to 0.28; P = 0.00) compared to that of the Medusa pattern group, − 0.13 ± 0.18 (95% CI, − 0.48 to 0.22; P = 0.469) compared to that of the tangled pattern group, and − 0.44 ± 0.20 (95% CI, − 0.61 to − 0.08; P = 0.01) compared to that of the other pattern group. The mean CMTs of the four MNV pattern groups were all decreased after treatment, including most notably in the other pattern group. However, there was no significant difference in the total change in CMT between different pattern groups ( P = 0.114). Considering MNV parameters, the mean MNV-VAs of the four MNV pattern groups were all decreased after treatment, including most notably in the seafan pattern group (from 1.33 ± 0.90 mm 2 to 0.57 ± 0.41 mm 2 , P = 0.225). The comparison of the change degree between the four MNV pattern groups showed that the change in the seafan pattern group was − 0.73 ± 0.44mm 2 (95% CI, − 1.6 to 0.13; P = 0.095) compared to that of the Medusa pattern group, − 0.16 ± 0.45mm 2 (95% CI, − 1.05 to 0.73; P = 0.722) compared to that of the tangled pattern group, and − 1.04 ± 0.41 mm 2 (95% CI, − 1.85 to − 0.23; P = 0.012) compared to that of the other pattern group. The mean MNV-VD ratios of the four pattern groups were all decreased at the last visit after treatment, including most notably in the other pattern group (from 0.40 ± 0.01 to 0.28 ± 0.04, P = 0.109), but there was no significant difference in the total change in MNV-VD ratio between the different pattern groups. The comparison of changes in BCVA and CMT between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig. 4 and Table 4. The comparison of changes in MNV parameters between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig. 5 and Table 5. An example case of a patient with seafan pattern MNV is shown in Fig. 6 . 3.4 Comparisons Between the Two Treatment Groups The mean BCVA, CMT, and MNV parameters of the two groups were not significantly different between pre-injection and at the last visit (90 days) after injection. These data are shown in Table 6 . Table 6 Mean BCVA, CMT and MNV Parameters Obtained From Neovascular AMD Patients Before and After Intravitreal Injection Group Mean BCVA (LogMAR) Mean CMT(µm) Mean MNV-VA(mm 2 ) Mean MNV-VD ratio Baseline 90days Baseline 90days Baseline 90days Baseline 90days Conbercept (n = 26) 0.97 ± 0.50 0.78 ± 0.53 293.71 ± 145.60 211.94 ± 51.11 1.34 ± 1.14 0.79 ± 0.59 0.40 ± 0.10 0.34 ± 0.12 Ranibizumab (n = 18) 0.94 ± 0.54 0.70 ± 0.47 328.72 ± 144.80 200.51 ± 90.29 0.87 ± 0.71 0.47 ± 0.35 0.39 ± 0.06 0.31 ± 0.11 P value 0.831 0.639 0.527 0.527 0.166 0.086 0.596 0.573 Baseline and post-injection data are presented as means ± standard deviations; AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; CMT, central macular thickness; MNV-VA, MNV, macular neovascularization; MNV vascular area; MNV-VD ratio, MNV vascular density ratio; P < 0.05 was considered to be statistically significant. 4. Discussion MNV, which used to be called choroidal neovascularization (CNV), is a pathologic essence of nAMD. The new nomenclature system mainly divides MNV into three types: type 1 MNV includes occult CNV and polypoidal choroidal vasculopathy (PCV), type 2 MNV is equivalent to classic CNV, and type 3 MNV mainly refers to neovascularization that originates from the deep capillary plexus of the retinal circulation and grows toward the outer retina [ 17 ]. This update to the standardized nomenclature system comes from the integration of concepts informed by recent advances in imaging technology. Multimodal image technology is used in various fundus diseases today. For vascular-related retinal diseases, especially nAMD, which is a major cause of irreversible visual impairment in people aged > 50 years worldwide [ 18 ], OCTA has become the main tool for MNV evaluation and analysis, with its non-invasive and repeatable advantages. From previous studies, we know that the detection rate of MNV is affected by multiple factors, such as PED, and type 2 MNV is easier to detect than type 1 MNV. However, the sensitivity of MNV detection by OCTA is not second to ICGA (55–90%), and OCTA can identify the morphology and details of MNV better [ 11 , 19 – 22 ]. In the current study, we enrolled 39 patients with clinically active lesions and found a rate of MNV detection by OCTA of 100%. Meanwhile, a well-defined and clearly distinguishable morphology neovascular complex was identified in 38 of 44 eyes (86.3%). Our results are similar to those of previous studies. Different studies have described and evaluated MNV based on morphological characteristics of MNV detected by OCTA. El Ameen et al. identified two distinct type 2 morphologies: the Medusa and the glomerulus patterns. The authors describe these two patterns as usually connected to a main branch [ 23 ]. De Carlo et al. used a fiber to describe the morphology of MNV [ 24 ]. Kuehlewein et al. reported 55% had the Medusa type, 21% had the seafan type, and 24% had an indistinct type among highly organized CNV lesions of eyes by OCTA [ 25 ]. However, these studies did not further explore the clinical significance of different patterns. In a retrospective study of 184 eyes, Karacorlu et al. linked type 1, type 2, and mixed-type neovascularization to nAMD using OCTA. They reported all clinically active cases had a well-defined pattern, such as Medusa and seafan patterns, but half (47%) of clinically inactive cases had an ill-defined, unidentifiable morphology. Their research findings showed that morphology on OCTA is not associated with clinical activity, except that the presence of long, dilated filamentous linear vessels was associated with chronicity and lesion inactivity [ 26 ]. Tew et al. further distinguished between and reported tangled pattern complexes with a main trunk or feeder vessel. They identified MNV in 110 out of 140 eyes (78.6%) using OCTA and classified 37.3% as having the Medusa pattern, 39.1% as having the seafan pattern, and 23.6% as having tangled pattern [ 16 ]. In our series, 12 (27.2%) eyes were classified as having the Medusa pattern, 16 (36.3%) had the seafan pattern, 10 (22.7%) had the tangled pattern, and 16 (13.6%) had the other pattern (i.e., ill-defined but measurable MNV). Similar to the results from Tew et al, there was a greater proportion of eyes with the seafan pattern in our study [ 27 ]. Many researchers have studied the structural parameters of MNV and tried to explore whether the differences of these parameters relate to the prognosis of anti-VEGF treatment. In our study, the results show that the overall BCVAs of the four MNV pattern groups improved and the structural parameters decreased after anti-VEGF treatment. Both drug treatment groups showed a decrease in CMT with an accompanying increase in visual acuity, with both being statistically significant changes between before and after treatment. This finding concurs with recent and established literature on nAMD, such as the CATT study [ 27 , 28 ]. In terms of MNV parameters, MNV-VA and the MNV-VD ratio decreased after anti-VEGF treatment compared to baseline, and the differences in the conbercept group but not the ranibizumab group were statistically significant. The effectiveness of anti-VEGF treatment on the different patterns of MNV has been verified in several studies [ 16 , 29 , 30 ]. In our study, we found that the visual acuity of patients with the tangled pattern was significantly improved at five postoperative time points after conbercept injection, and the change in BCVA improvement was greater for these patients than for those with the other three patterns. Our findings are consistent with those of Tew et al. [ 16 ], who suggested that MNV without a main trunk vessel and better baseline vision were benign factors for visual prognosis. However, they also differ in that the baseline vision of patients with the tangled pattern in our study was not the best. We also found that the MNV-VA and MNV-VD ratio of Medusa pattern patients were significantly reduced after conbercept injection in a statistically significant manner compared to patients with the other three patterns, but the decrease in MNV parameters existed without an accompanying increase in visual acuity; meanwhile, the change in BCVA improvement was also minimal throughout the whole experimental observation period. One study reported that OCTA features of active MNV include a higher rate of prominent central vessels, tiny and dense branching vessels, and peripheral arcades in active lesions [ 31 ]. The presence of thick central main vessels and active lesions often suggests the chronic course of mature neovascularization. Patients with the chronic, mature type of MNV are most likely to have an incomplete response to anti-VEGF therapy and problems with less vision recovery. Our results are consistent with those of Mettu et al.; the changes in area and density are related to decreases in the number and diameter of branching vessels [ 32 ]. Interestingly, our study results showed that the visual acuity and MNV-VA of patients with the seafan pattern were significantly improved and decreased in the ranibizumab treatment group. The change in BCVA improvement was significantly different, but the change in MNV-VA decrease was not. Kuehlewein et al. [ 25 ]. previously reported that some type 1 MNV patients had the seafan pattern and speculated that the reason for BCVA improvement in patients with seafan after ranibizumab therapy may be because the small molecular structure allowed ranibizumab to get though the RPE layer. We further observed a decrease in the MNV-VA at T3 (7 days after first injection), but there was some recovery at T4 (30 days after first injection), with corresponding increases and decreases in visual acuity at the same times. Bruno et al. concluded that there was a "cycle" of MNV growth: 24 h after injection, OCTA showed a decrease in neovascularization, and vessels were obviously "broken." By "pruning" thinner anastomotic stoma and "losing" smaller vessels, the MNV area was reduced, and the vascular trunk was visible on the 7th to 10th day, when the MNV area continued to decrease. However, re-proliferation of vessels was detected by OCTA at 28–35 days after injection, and some anastomoses and rings began to reappear where the vessels had "collapsed" [ 33 ]. Told et al. also concluded that anti-VEGF drugs can periodically inhibit and stop angiogenesis and prompt MNV neovascular buds to undergo the process of germination, pruning, and leakage [ 34 ]. Our results match the above research. In our study, 6 of the 44 eyes (13.6%) had other MNV, which were defined as having an ill-defined shape but one that can be measured, mainly showing irregular "dendritic," "filamentous," and "circular" patterns. The change in CMT decrease was significant. The long linear vessels were classified as inactive lesions with less vascular leakage, and anti-VEGF drugs can be used as anti-leakage agents with good response [ 26 , 35 ] [ 36 , 37 ]. In the present study, statistical differences between the two drug treatment groups were not found in BCVA, CMT, and MNV parameters. According to the “3 + PRN” regimen of anti-VEGF drugs, the visual gain at 3 months after injection can be used to predict the long-term visual prognosis [ 16 ]. Rush et al. published a study stating that changes in CNV size on ICG angiography after anti-VEGF therapy 2 months later may help the clinician to predict the clinical course of nAMD subjects [ 38 ]. Our study provides quantitative follow-up data of 2 anti-VEGF drugs for 3 months given under the “3 + PRN” treatment regimen. Follow-up data for ≥ 12 months will be collected to verify our initial conclusions and conjectures. 5. Limitations There were several limitations of the current study. First, the present study used a prospective design, but the enrolled patients in the two treatment groups were not randomized and instead treated according to the patient’s will. Second, the number of included treatment-naive nAMD patients was relatively small, only six eyes had the other pattern of MNV, and the follow-up time of 3 months was shorter, leading to weaker conclusions. Undoubtedly, studies with a larger sample size and longer follow-times are required. Third, it is impossible to absolutely avoid technical bottlenecks, such as projection artifact, segmentation artifacts, and motion artifacts, when OCTA collects deep neovascularization blood flow data. This makes it impossible for this study to further refine and correspond the shape of MNV and the position of MNV (type 1/type 2/mixed MNV). 6. Conclusions In conclusion, during the present study, OCTA quantitative analysis was used to evaluate changes in different forms of MNV after patients received different anti-VEGF drugs, providing partial theoretical support and clinical reference for personalized clinical treatment and visual prognosis prediction. Declarations Conflicts of Interest The authors declare that there are no conflicts of interest regarding the publication of this paper. Statement of financial support The authors would like to thank all the patients and volunteers in the study for their valuable participation. This study was supported by the Natural Science Foundation of Shaanxi Province (No. 2022JM-517) and the Science and Technology Talents Support Program of Shaanxi Provincial People’s Hospital (No. 2021JY-37). Data Availability The raw/processed data required to reproduce these findings cannot be shared at this time as the data are also part of an ongoing study. References Jonasson F, Fisher DE, Eiriksdottir G et al (2014) Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study. Ophthalmology. 121:1766–1772 Afarid M, Azimi A, Malekzadeh M (2019) Evaluation of serum interferons in patients with age-related macular degeneration. J Res Med Sci 24:24 Apte RS, Chen DS, Ferrara N (2019) VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 176:1248–1264 Kim KJ, Li B, Winer J et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844 Schlottmann PG, Alezzandrini AA, Zas M et al (2017) New Treatment Modalities for Neovascular Age-Related Macular Degeneration. Asia Pac J Ophthalmol (Phila) 6:514–519 Nguyen QD, Das A, Do DV et al (2020) Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration. Ophthalmology 127:963–976 Borrelli E, Parravano M, Sacconi R et al (2020) Guidelines on Optical Coherence Tomography Angiography Imaging: 2020 Focused Update. Ophthalmol Ther 9:697–707 Borrelli E, Sarraf D, Freund KB et al (2018) OCT angiography and evaluation of the choroid and choroidal vascular disorders. Prog Retin Eye Res 67:30–55 Jia Y, Bailey ST, Wilson DJ et al (2014) Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology 121:435–1444 Liang MC, de Carlo TE, Baumal CR et al (2016) Correlation of spectral domain optical coherence tomography angiography and clinical activity in neovascular age-related macular degeneration. Retina 36:2265–2273 Inoue M, Jung JJ, Balaratnasingam C et al (2016) A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization. Invest Ophthalmol Vis Sci 57 :OCT314-323 Hsu CR, Lai TT, Hsieh YT et al (2021) Combined quantitative and qualitative optical coherence tomography angiography biomarkers for predicting active neovascular age-related macular degeneration. Sci Rep 11:18068 Arrigo A, Aragona E, Bordato A et al (2021) Quantitative optical coherence tomography angiography parameter variations after treatment of macular neovascularization secondary to age-related macular degeneration. Retina 41:1463–1469 Shin YI, Kim JM, Lee MW et al (2020) Characteristics of the Foveal Microvasculature in Asian Patients with Dry Age-Related Macular Degeneration: An Optical Coherence Tomography Angiography Study. Ophthalmologica 243:145–153 Su L, Ji YS, Tong N et al (2020) Quantitative assessment of the retinal microvasculature and choriocapillaris in myopic patients using swept-source optical coherence tomography angiography. Graefes Arch Clin Exp Ophthalmol 258:1173–1180 Tew TB, Lai TT, Hsieh YT et al (2020) Comparison of different morphologies of choroidal neovascularization evaluated by ocular coherence tomography angiography in age-related macular degeneration. Clin Exp Ophthalmol 48:927–937 Spaide RF, Jaffe GJ, Sarraf D et al (2020) Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. Ophthalmology 127:616–636 Takeuchi J, Kataoka K, Ito Y et al (2018) Optical Coherence Tomography Angiography to Quantify Choroidal Neovascularization in Response to Aflibercept. Ophthalmologica 240:90–98 Liang MC, de Carlo TE, Baumal CR et al (2016) Correlation of Spectral Domain Optical Coherence Tomography Angiography and Clinical Activity in Neovascular Age-Related Macular Degeneration. Retina 36:2265–2273 Eandi CM, Ciardella A, Parravano M et al (2017) Indocyanine Green Angiography and Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 58:3690–3696 Coscas GJ, Lupidi M, Coscas F et al (2015) Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration: A new diagnostic challenge. Retina 35:2219–2228 Roberts PK, Nesper PL, Gill MK et al(2017) SEMIAUTOMATED QUANTITATIVE APPROACH TO CHARACTERIZE TREATMENT RESPONSE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Real-World Study. Retina 37:1492–1498 El Ameen A, Cohen SY, Semoun O et al (2015) Type 2 neovascularization secondary to age-related macular degeneration imaged by optical coherence tomography angiography. Retina 35:2212–2218 de Carlo TE, Bonini Filho MA, Chin AT et al (2015) Spectral-domain optical coherence tomography angiography of choroidal neovascularization. Ophthalmology 122:1228–1238 Kuehlewein L, Bansal M, Lenis TL et al (2015) Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration. Am J Ophthalmol 160:739–748 Karacorlu M, Sayman Muslubas I, Arf S et al (2019) Membrane patterns in eyes with choroidal neovascularization on optical coherence tomography angiography. Eye (Lond) 33:1280–1289 Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.Ophthalmology 119:1388–1398 Kanadani TCM, Veloso CE, Nehemy MB et al (2018) Subfoveal Choroidal Thickness in Eyes with Neovascular Age-Related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents. Ophthalmologica 240:200–207 Miere A, Butori P, Cohen SY et al (2019) Vascular remodeling of choroidal neovascularization after anti–vascular endothelial growth factor therapy visualized on optical coherence tomography angiography. Retina 39:548–557 Miere A, Semoun O, Cohen SY et al (2015) Optical coherence tomography angiography features of subretinal fibrosis in age-related macular degeneration. Retina 35:2275–2284 Al-Sheikh M, Iafe NA, Phasukkijwatana N et al (2018) Biomarkers of neovascular activity in age-related macular degeneration using optical coherence tomography angiography. Retina 38:220–230 Levine ES, Custo Greig E, Mendonça LSM et al (2020) The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration. Int J Retina Vitreous 6:39 Lumbroso B, Rispoli M, Savastano MC et al (2015) Longitudinal optical coherence tomography–angiography study of type 2 naive choroidal neovascularization early response after treatment. Retina 35:2242–2251 Told R, Reiter GS, Schranz M et al (2021) Correlation of Retinal Thickness and Swept-Source Optical Coherence Tomography Angiography Derived Vascular Changes in Patients with Neovascular Age-Related Macular Degeneration.Curr Eye Res 46:1002–1009 Arrigo A, Aragona E, Bordato A et al (2021) Morphological and Functional Relationship Between OCTA and FA/ICGA Quantitative Features in AMD-Related Macular Neovascularization. Front Med (Lausanne) 8:758668 Ahmed M, Syrine BM, Nadia BA et al (2021) Optical coherence tomography angiography features of macular neovascularization in wet age-related macular degeneration: A cross-sectional study. Ann Med Surg (Lond) 70:00776–00777 Carnevali A, Cicinelli MV, Capuano V et al (2016) Optical Coherence Tomography Angiography: A Useful Tool for Diagnosis of Treatment-Naive Quiescent Choroidal Neovascularization. Am J Ophthalmol 169:189–198 Rush RB, Rush SW, Aragon AV et al (2014) Evaluation of choroidal neovascularization with indocyanine green angiography in neovascular age-related macular degeneration subjects undergoing intravitreal bevacizumab therapy. Am J Ophthalmol 158:337–344 tables Tables 1-5 are not available with this version. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2326056","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":156268004,"identity":"9ad62522-db9b-4e53-af79-3308a7d9dead","order_by":0,"name":"Jing Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYBACPmYILcfG3n6AOC1sUC3GfDxnEojUAqUT50k4GBCphZ3HgJm37XB6mwRDAsOPim3EOIwtAaQlt0268QBjz5nbxGhhPv47d9vt3DaZAwnMjG1EaWFsYAZqSWeTSDAgVgvzAZCWBFK0AP3y999/wzZgIB8kyi/8/GcMGGecSZOXb28/+OBHBRFaUMABEtWPglEwCkbBKMAFAKgjMtxIP5TnAAAAAElFTkSuQmCC","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":156268005,"identity":"5abcdf0a-524d-4f15-beb2-c91d63fe487c","order_by":1,"name":"Zhufang Yang","email":"","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhufang","middleName":"","lastName":"Yang","suffix":""},{"id":156268006,"identity":"5ad1b78f-b9b8-4651-9c57-0ba9782e4068","order_by":2,"name":"Xueying Li","email":"","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xueying","middleName":"","lastName":"Li","suffix":""},{"id":156268007,"identity":"a0415a15-55b5-47b6-9190-00ab3edafc23","order_by":3,"name":"Di Li","email":"","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Di","middleName":"","lastName":"Li","suffix":""},{"id":156268008,"identity":"ff37981d-894f-4ede-8726-a6ef50019cc9","order_by":4,"name":"Jin Yang","email":"","orcid":"","institution":"Shaanxi Provincial People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Yang","suffix":""},{"id":156268010,"identity":"802de912-59b3-483a-a1c9-061e70ee5c6d","order_by":5,"name":"Meijia Dang","email":"","orcid":"","institution":"Xi'an Medical College","correspondingAuthor":false,"prefix":"","firstName":"Meijia","middleName":"","lastName":"Dang","suffix":""}],"badges":[],"createdAt":"2022-11-29 15:29:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2326056/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2326056/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":29832522,"identity":"70ac914a-2778-47f0-97be-48014507d758","added_by":"auto","created_at":"2022-12-02 18:05:33","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":253730,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of best-corrected visual acuity (BCVA) and central macular thickness (CMT) before and after treatment for eyes with four macular neovascularization (MNV) patterns of neovascular membrane on optical coherence tomography angiography. The top row shows mean BCVA values (left) and adjusted mean difference changes in the mean BCVA (right) from the baseline to after treatment at different time points. The mean BCVAs of the four MNV pattern groups all tended to improve after injection. At different times post-treatment, the BCVA was significantly better in the tangled pattern group than the other three pattern groups. After baseline correction, the differences between groups were compared, and the change in BCVA improvement was most significant in the tangled pattern group. The bottom row shows mean CMT values (left) and adjusted mean difference changes in the mean CMT (right) from baseline to after treatment at different time points. Except for BCVA, the mean CMTs of the four MNV pattern groups all tended to decrease after injection, but the difference was not significant. Compared to baseline, there were significant differences at different times after treatment in each morphological group; after baseline correction, however, significant differences between the four MNV pattern groups were not observed.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/2b627706ff242f050ab66107.jpg"},{"id":29832515,"identity":"2f83e4e5-c1d2-4679-842d-fbae0cc9c2c9","added_by":"auto","created_at":"2022-12-02 18:05:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":248962,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of macular neovascularization (MNV) parameters between before and after treatment for eyes with four MNV patterns of neovascular membrane on optical coherence tomography angiography. The top row shows mean MNV-vascular area (MNV-VA) values (left) and adjusted mean difference changes in the mean MNV-VA (right) from baseline to after treatment at different time points. The mean MNV-VAs of the four MNV pattern groups all tended to decrease after injection. At different times post-treatment, the MNV-VA was significantly decreased in the Medusa pattern group compared to the other three pattern groups; after baseline correction, the difference between groups was compared, and the change in MNV-VA decrease was most significant in the Medusa pattern group. The bottom row shows mean MNV-vascular density (MNV-VD) ratio values (left) and adjusted mean difference changes in the mean MNV-VD ratio (right) from baseline to after treatment at different time points. The mean MNV-VD ratios of the four MNV pattern groups all tended to decrease after injection. Compared to baseline, there were significant differences at some times after treatment in the Medusa and tangled pattern groups; after baseline correction, however, significant differences between the four MNV pattern groups were not observed.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/d4cc0af0f3bea0ccc3111957.jpg"},{"id":29832513,"identity":"6104c5e1-0d07-4893-8911-f50a6f265770","added_by":"auto","created_at":"2022-12-02 18:05:29","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":643889,"visible":true,"origin":"","legend":"\u003cp\u003eOptical coherence tomography angiography (OCTA) images of an 83-year-old male patient with tangled pattern MNV who received IVC therapy in the left eye. Baseline visual acuity (VA), 1.3 logMAR; status, after three conbercept injections in 90 days. Top left: a 6 × 6 spectral-domain OCTA image shows the neovascular complex with globular lesions without main vascular entanglement compared to an OCTA en face projection image taken after conbercept injection (bottom left). Top center: analysis results of ImageJ software corresponding to post-treatment (bottom center). Top right: OCT image shows the presence of subretinal fluid. Bottom right: subretinal fluid was reduced and BCVA improved to 1.0 logMAR after conbercept injection at 3 months (90 days).\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/e31518d9261307ed65a5e03b.jpg"},{"id":29832525,"identity":"a58b57d3-a132-470b-814a-a3f349cab83d","added_by":"auto","created_at":"2022-12-02 18:05:33","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":235255,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of best-corrected visual acuity (BCVA) and central macular thickness (CMT) between before and after treatment for eyes with 4four macular neovascularization (MNV) patterns of neovascular membrane on optical coherence tomography angiography. The top row shows mean BCVA values (left) and adjusted mean difference changes in the mean BCVA (right) from baseline to after treatment at different time points. The mean BCVAs of the four MNV pattern groups all tended to improve after injection. At different times post-treatment, the BCVA was significantly better in the seafan pattern group than the other three pattern groups. After baseline correction, the differences between groups were compared, and the change in BCVA improvement was most significant in the seafan pattern group. The bottom row shows mean CMT values (left) and adjusted mean difference changes in the mean CMT (right) from baseline to after treatment at different time points. The mean CMT of the four MNV pattern groups all tended to decrease after injection. Compared to baseline, there were significant differences at different times after treatment in each morphological group; after baseline correction, however, although the CMT of the other pattern group decreased the most, significant differences between the four MNV pattern groups could not be found.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/b2c699657659dc273d1dcefc.jpg"},{"id":29832521,"identity":"577c6f22-929e-4df9-a0b7-c127d242bdf3","added_by":"auto","created_at":"2022-12-02 18:05:33","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":240543,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of macular neovascularization (MNV) parameters between before and after treatment for eyes with four MNV pattern of neovascular membrane on optical coherence tomography angiography. The top row shows mean MNV-vascular area (MNV-VA) values (left) and adjusted mean difference changes in the mean MNV-VA (right) from baseline to after treatment at different time points. The mean MNV-VAs of the four MNV pattern groups all tended to decrease after injection. At different times post-treatment, the MNV-VA was significantly decreased in the seafan pattern group compared to the other three pattern groups. After baseline correction, the differences between groups was compared, and the change in MNV-VA decrease was most significant in the seafan pattern group. The bottom row shows mean MNV-vascular density (MNV-VD) ratio values (left) and adjusted mean difference changes in the mean MNV-VD ratio (right) from baseline to after treatment at different time points. The mean MNV-VD ratios of the four MNV pattern groups all tended to decrease after injection most notably in the other pattern group; after baseline correction, significant differences between the four MNV pattern groups were not observed.\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/7eb40a7aae9773546ce90aba.jpg"},{"id":29832514,"identity":"35a6c09d-1a90-4a55-ac53-7097687043b5","added_by":"auto","created_at":"2022-12-02 18:05:29","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":544673,"visible":true,"origin":"","legend":"\u003cp\u003eOptical coherence tomography angiography (OCTA) images of a 57-year-old male patient with seafan pattern MNV who received IVR therapy in the right eye. Baseline visual acuity (VA), 1.3 logMAR; status, after three ranibizumab injections in 90 days. Top left: a 6 × 6 SD-OCTA image shows the neovascular complex with globular lesions without main vascular entanglement compared to an OCTA en face projection image after ranibizumab injection (bottom left). Top center: analysis results of ImageJ software corresponding to post-treatment (bottom center). Top right: OCT image shows the presence of subretinal fluid. Bottom right: subretinal fluid and subretinal hyper-reflective material were reduced; meanwhile, the BCVA improved to 0.9 logMAR after ranibizumab injection at 3 months (90 days).\u003c/p\u003e","description":"","filename":"Fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/20ee4968f45e36ee26483f49.jpg"},{"id":31384536,"identity":"d3ba7ab0-4647-4349-90c6-a689ec4756db","added_by":"auto","created_at":"2023-01-10 20:29:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1033792,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2326056/v1/5818bdaa-bccf-45da-ac9f-00feed5d86fe.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quantitative data analysis of optical coherence tomography angiography of different morphologies of macular neovascularization after intravitreal conbercept versus ranibizumab for neovascular age-related macular degeneration","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eNeovascular age-related macular degeneration (nAMD), also known as exudative AMD, is caused by damage to Bruch\u0026rsquo;s membrane, and pathological neovascularization progresses to the retinal pigment epithelium (RPE) and neurosensory retina through Bruch\u0026rsquo;s membrane damage, resulting in macular neovascularization (MNV). Owing to the abnormal structure of neovascularization, the formation of MNV will cause a series of pathological processes, such as exudation, bleeding, organization, and fibrotic scarring, resulting in the loss of central vision [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnti\u0026ndash;vascular endothelial growth factor (anti-VEGF) treatment has become the most important and effective therapeutic method for nAMD in clinic. Its effect stems from the finding that VEGF is the key cytokine related to ocular neovascularization [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. First-line intravitreal-injectable anti-VEGF drugs for the treatment of nAMD include ranibizumab (Genentech, Inc. and Novartis International AG, Basel, Switzerland), which is a representative of monoclonal antibodies, and aflibercept (Regeneron Pharmaceuticals Inc., Bayer Healthcare Company Limited, Leverkusen, Germany) and conbercept (KH902) (Lumitin; Chengdu Kanghong Biotech, Ltd., Sichuan, China), which are both soluble fusion protein agents [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. For most nAMD patients, anti-VEGF drugs can effectively inhibit the leakage and bleeding of MNV; however, the responses of nAMD patients with MNV to anti-VEGF therapy are heterogeneous, suggesting that the pathological basis for this condition is multifactorial in nature.\u003c/p\u003e \u003cp\u003eThe diagnosis of MNV is generally made using fluorescein angiography (FA) or indocyanine green angiography (ICGA), which can dynamically display the abnormal vessels and observed vascular leakage. Optical coherence tomography (OCT) angiography (OCTA) with a high sensitivity of detection of MNV in nAMD\u0026mdash;as a fast, safe, non-invasive, and repeatable imaging modality able to better illustrate the microvasculature of retina and choroid\u0026mdash;could realize a detailed visualization of different types of MNV [7.8]. Quantitative information regarding MNV flow and area can also been detected and obtained [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Several studies had described the morphological features and classified the \u0026ldquo;tangled\u0026rdquo; or \u0026ldquo;glomerulus\u0026rdquo; and \u0026ldquo;seafan\u0026rdquo; or \u0026ldquo;Medusa\u0026rdquo; types of MNV in nAMD using OCTA [10.11]. Investigators have assessed the evolution of OCTA qualitative and quantitative biomarkers, including branching capillaries, anastomoses and loops, peripheral arcade, and hypointense halo for MNV after anti-VEGF therapy in recent years [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Nevertheless, the variations in and clinical implications of OCTA quantitative data of different morphological patterns of MNV after anti-VEGF treatment remain unknown. Furthermore, as is known, the structure and mechanism differ between conbercept and ranibizumab, and no study has reported the OCTA quantitative outcomes of different morphological patterns MNV for nAMD treated with intravitreal injection of conbercept (IVC) compared to ranibizumab. In addition, the relationship between these OCTA quantitative parameters and visual prognosis after different anti-VEGF drug treatments remains under evaluation and inconclusive.\u003c/p\u003e \u003cp\u003eThe current study sought to analyze the quantitative parameters outcomes identified with OCTA examination after a \u0026ldquo;3\u0026thinsp;+\u0026thinsp;PRN\u0026rdquo; regimen of IVC or IVR in patients with different morphological patterns of MNV and compare the visual prognosis of different MNV morphologies after IVC or IVR treatment. To the best of our knowledge, this is the first study to evaluate quantitative parameters changes among the different MNV patterns identified by OCTA for nAMD patients treated with conbercept.\u003c/p\u003e"},{"header":"2. Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eThis prospective, interventional case series study was conducted at Shaanxi Provincial People\u0026rsquo;s Hospital (Xi\u0026rsquo;an, China). The study was approved by the ethics committee of Shaanxi Provincial People\u0026rsquo;s Hospital (Xi\u0026rsquo;an, China) in accordance with the Declaration of Helsinki. Written informed consent was obtained from each study subject before the intravitreal injection of anti-VEGF agents was performed.we had access to information that could identify individual participants during or after data collection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study Subjects\u003c/h2\u003e \u003cp\u003eThis study recruited 39 patients with nAMD who were given an intravitreal injection of ranibizumab or conbercept at Shaanxi Provincial People\u0026rsquo;s Hospital between April 2020 and August 2021. Only patients who had not previously received any treatment for nAMD were enrolled; in other words, all participants enrolled in the present study were treatment-naive. The inclusion criteria for the patients with nAMD were as follows: (1) Age\u0026thinsp;\u0026ge;\u0026thinsp;50 years; (2) OCT/OCTA showed intra/subretinal fluid (IRF/SRF) or retinal pigment epithelium detachment (PED); (3) MNV was defined by FA, ICGA, and OCTA; and (4) the patient relatively clearly showed either the \"Medusa,\" \" seafan,\" or \"tangled\" type of MNV. The exclusion criteria for this study were as follows: (1) systemic and ocular diseases that cause changes in fundus vasculopathy (e.g., diabetic retinopathy, retinal vascular obstruction); (2) another ocular maculopathy causing MNV (e.g., polypoidal choroidal vasculopathy, myopic maculopathy, central serous chorioretinopathy, macular telangiectasia); (3) the refractive stroma was obviously turbid and cannot cooperate with the examination; and (4) a history of previous eye surgery or therapy except cataract (e.g., vitrectomy, photodynamic therapy, other drug injection).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Treatment\u003c/h2\u003e \u003cp\u003eTwenty-six eyes of 23 patients received treatment with conbercept (0.5 mg/0.05 mL) and 18 eyes of 16 patients were treated with ranibizumab (0.5 mg/0.05 mL). The procedure of intravitreal injection was performed by the same retina specialist (J. L.). The treatment protocols followed the \"3\u0026thinsp;+\u0026thinsp;PRN\" regimen. All intravitreal injections were strict aseptic operations performed after topical administration using povidone\u0026ndash;iodine. The topical antibiotic levofloxacin was given 3 days before or after injection. All of the patients underwent preoperative and postoperative comprehensive ophthalmologic examinations, including slit-lamp biomicroscopy and dilated fundus examination.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Data Collection, Image Acquisition, and Analysis\u003c/h2\u003e \u003cp\u003eThe baseline characteristics of all enrolled patients, such as age, gender, and past history, were recorded. The best-corrected visual acuity (BCVA) was measured and recorded by the same clinician and converted according to the minimum resolution angle logarithm (logMAR) visual acuity.\u003c/p\u003e \u003cp\u003eWe used a 512 \u0026times; 128 scanning mode to measure the central macular thickness (CMT) (internal limiting membrane [ILM] to RPE distance) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Using depth enhancement, the artifact removal model was used to track the retina of the same level of the deep macular 6 \u0026times; 6 mm\u003csup\u003e2\u003c/sup\u003e region until 2 scans of good quality were obtained. The OCT-based optical microangiography (OMAG) algorithm can detect the amplitude and phase changes between continuous B-scans at the same position, quantify the motion contrast, and generate the OCTA image [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Using the built-in OCTA software to manually divide the RPE layer to extract the lesser profile image, we analyzed and recorded the RPE\u0026ndash;RPE fit level using OCTA, manually fine-tuned the boundary line to display the clearest MNV morphology and record the value section, and ensured that six images were acquired at the same RPE level to reduce errors. First, we saved the images in a unified format and then imported into the ImageJ software (U.S. National Institutes of Health, Bethesda, MD, USA) to threshold and binarize the pixel intensity. Then, we enlarged each image 800 times, and measured the area of MNV blood vessels by manually sketching the visible blood vessels with a line 1 pixel wide. The vascular density ratio was defined as the ratio of the total pixel area of 6 \u0026times; 6 mm\u003csup\u003e2\u003c/sup\u003e scanned area occupied by vessels in red pixels. The scale conversion relationship was 68.8335 (PX)\u0026thinsp;=\u0026thinsp;1 mm.\u003c/p\u003e \u003cp\u003eAll included patients with neovascular AMD and MNV were exactly examined and diagnosed by the same retina specialist (J. L.) for OCTA examination (CIRRUS HD-OCT model 5000 with AngioPlex\u0026reg;; Carl Zeiss Meditec, Jena, Germany). The baseline and structural data collected before the injection (T1) and at 1 day (T2), 7 days (T3), 30 days (T4), 60 days (T5), and 90 days (T6) after anti-VEGF treatment were collected and analyzed. The BCVA, MNV vascular area (MNV-VA), MNV vascular density ratio (MNV-VD ratio), and (CMT) were compared between before and after treatment.\u003c/p\u003e \u003cp\u003eMorphological patterns of the MNV complex on OCTA were studied and classified into four groups, as follows: 1) the \u0026ldquo;Medusa\u0026rdquo; pattern, defined as a lesion with branching vessels radiating in all direction from the main vessel trunk at the center; 2) the \u0026ldquo;seafan\u0026rdquo; pattern, defined as a lesion with branching vessels radiating from one side of the main vessel trunk; 3) the \u0026ldquo;tangled\u0026rdquo; pattern, defined as a lesion with globular structures of entwined vessels without a main vessel trunk [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]; and 4) the \u0026ldquo;other\u0026rdquo; pattern, defined as a lesion with an irregular vessel that can't be attributed to the above three forms but can still be measured.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS 26.0 (IBM Corporation, Armonk, NY, USA). Non-parametric statistical methods were used: the Wilcoxon signed-rank test was used to compare the variables of within group differences of different morphology groups before and after treatment, whereas Fisher\u0026rsquo;s exact test was used for categorical variables and Friedman\u0026rsquo;s test was used for continuous variables. We used backward elimination of generalized estimating equation (GEE) modeling to evaluate differences between the four OCTA pattern groups after baseline correction. Confidence intervals (CIs) were also calculated using GEE modeling. The model included the time that had elapsed since enrollment, treatment assignment, and interaction between time and treatment. A 2-sided \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1 Participant Baseline Characteristics\u003c/h2\u003e\n\u003cp\u003eThe baseline characteristics of the study participants are listed in Table\u0026nbsp;1. No age or gender differences were found between the IVC treatment group and IVR treatment group. Thirty-nine nAMD patients, including 17 men and 22 women, with 44 eyes of interest with MNV were included for analysis in this study, stratified as 26 eyes of 23 patients in the IVC group and 18 eyes of 16 patients in the IVR group. The median age of IVC group patients was 61 (range, 50\u0026ndash;83) years, and 13 were male and 10 were female. The mean baseline BCVA, CMT, MNV-VA, and MNV-VD ratio values were 0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50 logMAR, 293.71\u0026thinsp;\u0026plusmn;\u0026thinsp;145.60 mm, 1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14 mm\u003csup\u003e2\u003c/sup\u003e, and 0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10. Of the 26 eyes that showed a distinct MNV complex on OCTA, the Medusa, seafan, tangled, and other patterns were detected in 9 eyes (34.6%), 9 eyes (34.6%), 5 eyes (19.2%), and 3 eyes (11.5%), respectively. The IVR group included 4 men and 12 women with a mean age of 71.61\u0026thinsp;\u0026plusmn;\u0026thinsp;11.05 (range, 51\u0026ndash;91) years; their mean baseline BCVA, CMT, MNV-VA, and MNV-VD ratio values was 0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54 logMAR, 328.72\u0026thinsp;\u0026plusmn;\u0026thinsp;144.80 mm, 0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71 mm\u003csup\u003e2\u003c/sup\u003e, and 0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06. Of the 18 eyes with MNV in this group, the Medusa, seafan, tangled, and other patterns were detected in 3 eyes (16.7%), 7 eyes (38.9%), 5 eyes (27.8%), and 3 eyes (16.7%). All enrolled patients were observed for 3 months, and no ocular or systemic adverse events were recorded.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003e3.2 Comparisons of Outcomes in the IVC Treatment Group\u003c/h2\u003e\n\u003cp\u003eTwenty-six eyes of 23 patients received primary IVC treatment. At 90 days after treatment, the mean BCVA had improved in the overall cohort from 0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50 logMAR at baseline to 0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53 logMAR at the last visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Reductions in the mean CMT (from 293.71\u0026thinsp;\u0026plusmn;\u0026thinsp;145.60 \u0026micro;m to 211.94\u0026thinsp;\u0026plusmn;\u0026thinsp;51.11 \u0026micro;m, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), the mean MNV-VA (from 1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14 mm\u003csup\u003e2\u003c/sup\u003e to 0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), and the mean MNV-VD ratio (from 0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 to 0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037) were noticed after treatment compared to baseline. The mean BCVA of tangled pattern eyes improved from 0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60 logMAR at baseline to 0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38 logMAR at the last visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and the degree of BCVA improvement was also significantly higher for patients with the tangled pattern than those with the other three patterns. Specifically, the change associated with the tangled pattern was \u0026minus;\u0026thinsp;0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 (95% CI, \u0026minus;\u0026thinsp;0.7 to \u0026minus;\u0026thinsp;0.17; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) compared to that of the Medusa pattern group, \u0026minus;\u0026thinsp;0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 (95% CI, \u0026minus;\u0026thinsp;0.57 to \u0026minus;\u0026thinsp;0.04; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023), compared to that of the seafan pattern group, and \u0026minus;\u0026thinsp;0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 (95% CI, \u0026minus;\u0026thinsp;0.61 to \u0026minus;\u0026thinsp;0.08; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) compared to that of the other pattern group, respectively.\u003c/p\u003e\n\u003cp\u003eThe mean CMTs of the four MNV patterns were all decreased after treatment, including most notably in patients with the other pattern, but there was no significant difference in the total change of CMT between the different pattern groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.052). Considering MNV parameters, the Medusa pattern eyes showed a significant reduction in mean MNV-VA after treatment at the last visit (from 2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36 mm\u003csup\u003e2\u003c/sup\u003e to 0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). The comparison of the change degree of the four MNV patterns showed that the change in the Medusa pattern group was \u0026minus;\u0026thinsp;1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40 mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;1.82 to \u0026minus;\u0026thinsp;0.27; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) compared to that of the tangled pattern group, \u0026minus;\u0026thinsp;1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50 mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;2 to \u0026minus;\u0026thinsp;0.05; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038) compared to that of the seafan pattern group, and \u0026minus;\u0026thinsp;1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;2.05 to \u0026minus;\u0026thinsp;0.45; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) compared to that of the other pattern group, respectively. Therefore, the mean MNV-VA of patients with the Medusa pattern in the IVC group decreased the most.\u003c/p\u003e\n\u003cp\u003eThe mean MNV-VD ratios of the four MNV patterns were all decreased at the last visit after treatment compared to baseline, most notably in the Medusa pattern group; however, the changes of all MNV patterns were not significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.107). The comparison of changes in BCVA and CMT between before and after conbercept treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;2. The comparison of variation in MNV parameters between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;3. An example case of a patient with tangled pattern MNV is shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003e3.3 Comparisons of Outcomes in the IVR Treatment Group\u003c/h2\u003e\n\u003cp\u003eEighteen eyes of 16 patients received primary IVR treatment. At 90 days after treatment, the mean BCVA had improved in the overall cohort from 0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54 logMAR at baseline to 0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47 logMAR at the last visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014). Reductions in the mean CMT (from 328.72\u0026thinsp;\u0026plusmn;\u0026thinsp;144.80 \u0026micro;m to 200.51\u0026thinsp;\u0026plusmn;\u0026thinsp;90.29 \u0026micro;m, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), the mean MNV-VA (from 0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71 mm\u003csup\u003e2\u003c/sup\u003e to 0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.133), and the mean MNV-VD ratio (from 0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 to 0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05) were also noticed. The mean BCVA improvement and CMT decrease between before and after treatment in the overall cohort were statistically significant, while the changes in the mean MNV-VA and MNV-VD ratio were not. The mean BCVA of seafan pattern eyes improved from 0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40 logMAR at baseline to 0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32 logMAR at the last visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042), and the change in BCVA improvement was also significantly greater for the seafan pattern than the other three patterns; specifically, the change in the seafan pattern group was \u0026minus;\u0026thinsp;0.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 (95% CI, \u0026minus;\u0026thinsp;0.69 to 0.28; P\u0026thinsp;=\u0026thinsp;0.00) compared to that of the Medusa pattern group, \u0026minus;\u0026thinsp;0.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 (95% CI, \u0026minus;\u0026thinsp;0.48 to 0.22; P\u0026thinsp;=\u0026thinsp;0.469) compared to that of the tangled pattern group, and \u0026minus;\u0026thinsp;0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20 (95% CI, \u0026minus;\u0026thinsp;0.61 to \u0026minus;\u0026thinsp;0.08; P\u0026thinsp;=\u0026thinsp;0.01) compared to that of the other pattern group.\u003c/p\u003e\n\u003cp\u003eThe mean CMTs of the four MNV pattern groups were all decreased after treatment, including most notably in the other pattern group. However, there was no significant difference in the total change in CMT between different pattern groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.114). Considering MNV parameters, the mean MNV-VAs of the four MNV pattern groups were all decreased after treatment, including most notably in the seafan pattern group (from 1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90 mm\u003csup\u003e2\u003c/sup\u003e to 0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.225). The comparison of the change degree between the four MNV pattern groups showed that the change in the seafan pattern group was \u0026minus;\u0026thinsp;0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;1.6 to 0.13; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.095) compared to that of the Medusa pattern group, \u0026minus;\u0026thinsp;0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;1.05 to 0.73; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.722) compared to that of the tangled pattern group, and \u0026minus;\u0026thinsp;1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 mm\u003csup\u003e2\u003c/sup\u003e (95% CI, \u0026minus;\u0026thinsp;1.85 to \u0026minus;\u0026thinsp;0.23; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) compared to that of the other pattern group.\u003c/p\u003e\n\u003cp\u003eThe mean MNV-VD ratios of the four pattern groups were all decreased at the last visit after treatment, including most notably in the other pattern group (from 0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 to 0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.109), but there was no significant difference in the total change in MNV-VD ratio between the different pattern groups. The comparison of changes in BCVA and CMT between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Table\u0026nbsp;4. The comparison of changes in MNV parameters between before and after treatment at different time points in the four MNV pattern groups on OCTA are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e and Table\u0026nbsp;5. An example case of a patient with seafan pattern MNV is shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003e3.4 Comparisons Between the Two Treatment Groups\u003c/h2\u003e\n\u003cp\u003eThe mean BCVA, CMT, and MNV parameters of the two groups were not significantly different between pre-injection and at the last visit (90 days) after injection. These data are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMean BCVA, CMT and MNV Parameters Obtained From Neovascular AMD Patients Before and After Intravitreal Injection\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMean BCVA (LogMAR)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMean CMT(\u0026micro;m)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMean MNV-VA(mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMean MNV-VD ratio\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e90days\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e90days\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e90days\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e90days\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConbercept\u003c/p\u003e\n\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e293.71\u0026thinsp;\u0026plusmn;\u0026thinsp;145.60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e211.94\u0026thinsp;\u0026plusmn;\u0026thinsp;51.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRanibizumab\u003c/p\u003e\n\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e328.72\u0026thinsp;\u0026plusmn;\u0026thinsp;144.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e200.51\u0026thinsp;\u0026plusmn;\u0026thinsp;90.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.831\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.639\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.527\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.527\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.166\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.086\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.596\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.573\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eBaseline and post-injection data are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations; AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; CMT, central macular thickness; MNV-VA, MNV, macular neovascularization; MNV vascular area; MNV-VD ratio, MNV vascular density ratio; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMNV, which used to be called choroidal neovascularization (CNV), is a pathologic essence of nAMD. The new nomenclature system mainly divides MNV into three types: type 1 MNV includes occult CNV and polypoidal choroidal vasculopathy (PCV), type 2 MNV is equivalent to classic CNV, and type 3 MNV mainly refers to neovascularization that originates from the deep capillary plexus of the retinal circulation and grows toward the outer retina [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This update to the standardized nomenclature system comes from the integration of concepts informed by recent advances in imaging technology. Multimodal image technology is used in various fundus diseases today. For vascular-related retinal diseases, especially nAMD, which is a major cause of irreversible visual impairment in people aged\u0026thinsp;\u0026gt;\u0026thinsp;50 years worldwide [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], OCTA has become the main tool for MNV evaluation and analysis, with its non-invasive and repeatable advantages. From previous studies, we know that the detection rate of MNV is affected by multiple factors, such as PED, and type 2 MNV is easier to detect than type 1 MNV. However, the sensitivity of MNV detection by OCTA is not second to ICGA (55\u0026ndash;90%), and OCTA can identify the morphology and details of MNV better [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In the current study, we enrolled 39 patients with clinically active lesions and found a rate of MNV detection by OCTA of 100%. Meanwhile, a well-defined and clearly distinguishable morphology neovascular complex was identified in 38 of 44 eyes (86.3%). Our results are similar to those of previous studies.\u003c/p\u003e \u003cp\u003eDifferent studies have described and evaluated MNV based on morphological characteristics of MNV detected by OCTA. El Ameen et al. identified two distinct type 2 morphologies: the Medusa and the glomerulus patterns. The authors describe these two patterns as usually connected to a main branch [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. De Carlo et al. used a fiber to describe the morphology of MNV [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Kuehlewein et al. reported 55% had the Medusa type, 21% had the seafan type, and 24% had an indistinct type among highly organized CNV lesions of eyes by OCTA [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, these studies did not further explore the clinical significance of different patterns. In a retrospective study of 184 eyes, Karacorlu et al. linked type 1, type 2, and mixed-type neovascularization to nAMD using OCTA. They reported all clinically active cases had a well-defined pattern, such as Medusa and seafan patterns, but half (47%) of clinically inactive cases had an ill-defined, unidentifiable morphology. Their research findings showed that morphology on OCTA is not associated with clinical activity, except that the presence of long, dilated filamentous linear vessels was associated with chronicity and lesion inactivity [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Tew et al. further distinguished between and reported tangled pattern complexes with a main trunk or feeder vessel. They identified MNV in 110 out of 140 eyes (78.6%) using OCTA and classified 37.3% as having the Medusa pattern, 39.1% as having the seafan pattern, and 23.6% as having tangled pattern [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In our series, 12 (27.2%) eyes were classified as having the Medusa pattern, 16 (36.3%) had the seafan pattern, 10 (22.7%) had the tangled pattern, and 16 (13.6%) had the other pattern (i.e., ill-defined but measurable MNV). Similar to the results from Tew et al, there was a greater proportion of eyes with the seafan pattern in our study [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany researchers have studied the structural parameters of MNV and tried to explore whether the differences of these parameters relate to the prognosis of anti-VEGF treatment. In our study, the results show that the overall BCVAs of the four MNV pattern groups improved and the structural parameters decreased after anti-VEGF treatment. Both drug treatment groups showed a decrease in CMT with an accompanying increase in visual acuity, with both being statistically significant changes between before and after treatment. This finding concurs with recent and established literature on nAMD, such as the CATT study [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In terms of MNV parameters, MNV-VA and the MNV-VD ratio decreased after anti-VEGF treatment compared to baseline, and the differences in the conbercept group but not the ranibizumab group were statistically significant. The effectiveness of anti-VEGF treatment on the different patterns of MNV has been verified in several studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In our study, we found that the visual acuity of patients with the tangled pattern was significantly improved at five postoperative time points after conbercept injection, and the change in BCVA improvement was greater for these patients than for those with the other three patterns. Our findings are consistent with those of Tew et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], who suggested that MNV without a main trunk vessel and better baseline vision were benign factors for visual prognosis. However, they also differ in that the baseline vision of patients with the tangled pattern in our study was not the best. We also found that the MNV-VA and MNV-VD ratio of Medusa pattern patients were significantly reduced after conbercept injection in a statistically significant manner compared to patients with the other three patterns, but the decrease in MNV parameters existed without an accompanying increase in visual acuity; meanwhile, the change in BCVA improvement was also minimal throughout the whole experimental observation period. One study reported that OCTA features of active MNV include a higher rate of prominent central vessels, tiny and dense branching vessels, and peripheral arcades in active lesions [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The presence of thick central main vessels and active lesions often suggests the chronic course of mature neovascularization. Patients with the chronic, mature type of MNV are most likely to have an incomplete response to anti-VEGF therapy and problems with less vision recovery. Our results are consistent with those of Mettu et al.; the changes in area and density are related to decreases in the number and diameter of branching vessels [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Interestingly, our study results showed that the visual acuity and MNV-VA of patients with the seafan pattern were significantly improved and decreased in the ranibizumab treatment group. The change in BCVA improvement was significantly different, but the change in MNV-VA decrease was not. Kuehlewein et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. previously reported that some type 1 MNV patients had the seafan pattern and speculated that the reason for BCVA improvement in patients with seafan after ranibizumab therapy may be because the small molecular structure allowed ranibizumab to get though the RPE layer. We further observed a decrease in the MNV-VA at T3 (7 days after first injection), but there was some recovery at T4 (30 days after first injection), with corresponding increases and decreases in visual acuity at the same times. Bruno et al. concluded that there was a \"cycle\" of MNV growth: 24 h after injection, OCTA showed a decrease in neovascularization, and vessels were obviously \"broken.\" By \"pruning\" thinner anastomotic stoma and \"losing\" smaller vessels, the MNV area was reduced, and the vascular trunk was visible on the 7th to 10th day, when the MNV area continued to decrease. However, re-proliferation of vessels was detected by OCTA at 28\u0026ndash;35 days after injection, and some anastomoses and rings began to reappear where the vessels had \"collapsed\" [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Told et al. also concluded that anti-VEGF drugs can periodically inhibit and stop angiogenesis and prompt MNV neovascular buds to undergo the process of germination, pruning, and leakage [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our results match the above research. In our study, 6 of the 44 eyes (13.6%) had other MNV, which were defined as having an ill-defined shape but one that can be measured, mainly showing irregular \"dendritic,\" \"filamentous,\" and \"circular\" patterns. The change in CMT decrease was significant. The long linear vessels were classified as inactive lesions with less vascular leakage, and anti-VEGF drugs can be used as anti-leakage agents with good response [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In the present study, statistical differences between the two drug treatment groups were not found in BCVA, CMT, and MNV parameters. According to the \u0026ldquo;3\u0026thinsp;+\u0026thinsp;PRN\u0026rdquo; regimen of anti-VEGF drugs, the visual gain at 3 months after injection can be used to predict the long-term visual prognosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Rush et al. published a study stating that changes in CNV size on ICG angiography after anti-VEGF therapy 2 months later may help the clinician to predict the clinical course of nAMD subjects [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Our study provides quantitative follow-up data of 2 anti-VEGF drugs for 3 months given under the \u0026ldquo;3\u0026thinsp;+\u0026thinsp;PRN\u0026rdquo; treatment regimen. Follow-up data for \u0026ge;\u0026thinsp;12 months will be collected to verify our initial conclusions and conjectures.\u003c/p\u003e"},{"header":"5. Limitations","content":"\u003cp\u003eThere were several limitations of the current study. First, the present study used a prospective design, but the enrolled patients in the two treatment groups were not randomized and instead treated according to the patient\u0026rsquo;s will. Second, the number of included treatment-naive nAMD patients was relatively small, only six eyes had the other pattern of MNV, and the follow-up time of 3 months was shorter, leading to weaker conclusions. Undoubtedly, studies with a larger sample size and longer follow-times are required. Third, it is impossible to absolutely avoid technical bottlenecks, such as projection artifact, segmentation artifacts, and motion artifacts, when OCTA collects deep neovascularization blood flow data. This makes it impossible for this study to further refine and correspond the shape of MNV and the position of MNV (type 1/type 2/mixed MNV).\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eIn conclusion, during the present study, OCTA quantitative analysis was used to evaluate changes in different forms of MNV after patients received different anti-VEGF drugs, providing partial theoretical support and clinical reference for personalized clinical treatment and visual prognosis prediction.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of financial support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the patients and volunteers in the study for their valuable participation. This study was supported by the Natural Science Foundation of Shaanxi Province (No. 2022JM-517) and the Science and Technology Talents Support Program of Shaanxi Provincial People\u0026rsquo;s Hospital (No. 2021JY-37).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw/processed data required to reproduce these findings cannot be shared at this time as the data are also part of an ongoing study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJonasson F, Fisher DE, Eiriksdottir G et al (2014) Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study. Ophthalmology. 121:1766\u0026ndash;1772\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfarid M, Azimi A, Malekzadeh M (2019) Evaluation of serum interferons in patients with age-related macular degeneration. 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Eye (Lond) 33:1280\u0026ndash;1289\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eComparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.Ophthalmology 119:1388\u0026ndash;1398\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanadani TCM, Veloso CE, Nehemy MB et al (2018) Subfoveal Choroidal Thickness in Eyes with Neovascular Age-Related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents. Ophthalmologica 240:200\u0026ndash;207\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiere A, Butori P, Cohen SY et al (2019) Vascular remodeling of choroidal neovascularization after anti\u0026ndash;vascular endothelial growth factor therapy visualized on optical coherence tomography angiography. 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Int J Retina Vitreous 6:39\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLumbroso B, Rispoli M, Savastano MC et al (2015) Longitudinal optical coherence tomography\u0026ndash;angiography study of type 2 naive choroidal neovascularization early response after treatment. Retina 35:2242\u0026ndash;2251\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTold R, Reiter GS, Schranz M et al (2021) Correlation of Retinal Thickness and Swept-Source Optical Coherence Tomography Angiography Derived Vascular Changes in Patients with Neovascular Age-Related Macular Degeneration.Curr Eye Res 46:1002\u0026ndash;1009\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArrigo A, Aragona E, Bordato A et al (2021) Morphological and Functional Relationship Between OCTA and FA/ICGA Quantitative Features in AMD-Related Macular Neovascularization. Front Med (Lausanne) 8:758668\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed M, Syrine BM, Nadia BA et al (2021) Optical coherence tomography angiography features of macular neovascularization in wet age-related macular degeneration: A cross-sectional study. Ann Med Surg (Lond) 70:00776\u0026ndash;00777\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarnevali A, Cicinelli MV, Capuano V et al (2016) Optical Coherence Tomography Angiography: A Useful Tool for Diagnosis of Treatment-Naive Quiescent Choroidal Neovascularization. Am J Ophthalmol 169:189\u0026ndash;198\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRush RB, Rush SW, Aragon AV et al (2014) Evaluation of choroidal neovascularization with indocyanine green angiography in neovascular age-related macular degeneration subjects undergoing intravitreal bevacizumab therapy. Am J Ophthalmol 158:337\u0026ndash;344\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"tables","content":"\u003cp\u003eTables 1-5 are not available with this version.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Macular neovascularization (MNV), Neovascular Age-related Macular Degeneration(nAMD), Morphological, anti Vascular Endothelial Growth Factor (VEGF), Optical Coherence Tomography Angiography (OCTA)","lastPublishedDoi":"10.21203/rs.3.rs-2326056/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2326056/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003ePurpose\u003c/b\u003e We sought to analyze quantitative data findings of optical coherence tomography angiography (OCTA) of different morphologies of macular neovascularization (MNV) in patients with neovascular age-related macular degeneration (nAMD) who received intravitreal conbercept (IVC) or ranibizumab (IVR).\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e This was a prospective, interventional case series study and involved 39 patients, including 23 treated with 0.05 mL of conbercept and 16 treated with 0.05 mL of ranibizumab. Patients with MNV were diagnosed with nAMD for the first time at Shaanxi People's Hospital and all were treated with the \"3\u0026thinsp;+\u0026thinsp;PRN\" regimen. These MNV cases could be further divided into four OCTA patterns: the \u0026ldquo;Medusa\u0026rdquo; pattern, the \u0026ldquo;tangled\u0026rdquo; pattern, the \u0026ldquo;seafan\u0026rdquo; pattern, and the \u0026ldquo;other\u0026rdquo; pattern. Patients were examined using OCTA before (T1) the injection and at 1 day (T2), 7 days (T3), 30 days (T4), 60 days (T5), and 90 days (T6) after anti\u0026ndash;vascular endothelial growth factor (VEGF) treatments. Main outcome measures included best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density ratio (MNV-VD ratio), and central macular thickness (CMT).\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e Forty-four eyes of 39 patients with nAMD (17 men and 22 women) were included. The average age of participants was 71.34\u0026thinsp;\u0026plusmn;\u0026thinsp;10.34 years (range, 50\u0026ndash;91 years). Twenty-eight eyes (23 patients) received IVC, and 18 eyes (16 patients) received IVR. At 90 days after treatment, the mean BCVAs of patients with the four patterns in the IVC group were improved (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002); notably, the tangled pattern patients had significantly better results than those with the other three patterns (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). Eyes with all four patterns showed significant CMT decreases from the baseline level at 90 days, but there was no significant difference in the total change of CMT between the eyes with different patterns (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.052). The mean MNV-VA and MNV-VD ratios were reduced in all four pattern groups, although the difference of the Medusa pattern was statistically significant for the mean MNV-VA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) but not the mean MNV-VD ratio (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.107). In the IVR group, among the four patterns, the patients with the seafan MNV pattern showed a more significant BCVA improvement (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042). The mean CMTs of four MNV patterns were decreased after treatment, most notably in patients with the other pattern, but there was no significant difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.114). Considering MNV parameters, the mean MNV-VA of the seafan pattern and the mean MNV-VD of the other pattern were significantly decreased, albeit without significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.225 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.109). For the comparison between the 2 groups, the mean BCVA, CMT, and MNV parameters were all not significantly different between pre-injection and at the last visit (90 days) after injection.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e The distinct morphologies of MNV in nAMD patients can be identified and quantitatively analyzed by OCTA. These different patterns might be useful and instructive predictors for the prognosis of nAMD patients after anti-VEGF therapy. Conbercept for patients with the tangled MNV pattern and ranibizumab for patients with the seafan MNV pattern may be considered as therapeutics.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTrial registration number\u003c/b\u003e ChiCTR2200056961\u003c/p\u003e","manuscriptTitle":"Quantitative data analysis of optical coherence tomography angiography of different morphologies of macular neovascularization after intravitreal conbercept versus ranibizumab for neovascular age-related macular degeneration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-12-02 18:04:45","doi":"10.21203/rs.3.rs-2326056/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f02858cf-28ea-4810-9219-9951a7692996","owner":[],"postedDate":"December 2nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-01-10T20:29:18+00:00","versionOfRecord":[],"versionCreatedAt":"2022-12-02 18:04:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2326056","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2326056","identity":"rs-2326056","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}