Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy

Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy | 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 Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy Xiaoying Huang, Minming Zheng, Jiatao Lu, Xi Wang, Zheng Zheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2608586/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Jun, 2023 Read the published version in BMC Ophthalmology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who received at least one intravitreal injection of anti-vascular endothelial growth factor therapy (VEGF) and lost to follow-up (LTFU) for more than six months were analyzed to investigate the factors contributing to the LTFU and the prognosis. Method: This was a retrospective, single-center study to analyze the causes and prognosis of LTFU over six months in RVO-ME patients treated with intravitreal anti-VEGF injections at our institution from January 2019 to August 2022 and to collect patients' baseline characteristics along with the number of injections before LTFU, primary disease, best corrected visual acuity (BCVA) before LTFU and after return visit, central macular thickness (CMT), months before LTFU and after LTFU, reasons for LTFU, and complications, to analyze the factors affecting visual outcome at a return visit. Results: This study included 125 patients with LTFU; 103 remained LTFU after six months, and 22 returned after LTFU. The common reason for LTFU was "no improvement in vision" (34.4%), followed by "transport inconvenience" (22.4%), 16 patients (12.8%) were unwilling to visit the clinic, 15 patients (12.0%) had already elected to seek treatment elsewhere, 12 patients (9.6%) were not seen in time due to the 2019-nCov epidemic, and 11 patients (8.8%) cannot do it due to financial reasons. The number of injections before LTFU was a risk factor for LTFU ( P < 0.05). LogMAR at the initial visit ( P < 0.001), CMT at the initial visit ( P < 0.05), CMT before the LTFU ( P < 0.001), and CMT after the return visit ( P < 0.05) were influential factors for logMAR at the return visit. Conclusion: Most RVO-ME patients were LTFU after anti-VEGF therapy. Long-term LTFU is greatly detrimental to the visual quality of patients; thus, the management of RVO-ME patients in follow-up should be considered. retinal vein occlusion anti-vascular endothelial growth factor loss of follow-up influential factors. Figures Figure 1 Figure 2 Introduction Retinal Vein Occlusion (RVO) is a secondary retinal vascular disease that commonly causes visual loss. Local ischemia and hypoxia in the retina cause an increase in the concentration of cytokines, including vascular endothelial growth factor (VEGF) and inflammatory factors, resulting in fluid accumulation in the inner and lower layers of the retina by disrupting the blood-retinal barrier to promote neovascularization and macular edema (ME) [ 1 , 2 ]. ME is the major cause of poor vision in RVO, while intravitreal injections of anti-VEGF drugs can effectively reduce intraocular VEGF concentrations, thereby decreasing central macular thickness (CMT) and ME [ 3 ]. The BRAVO and CRUISE trials are two large prospective randomized controlled trials demonstrating the effectiveness of intravitreal injections of ranibizumab in BRVO-ME and CRVO-ME [ 4 , 5 ]. Studies have demonstrated that RVO, especially CRVO, may require more frequent follow-up in the second year of treatment to maintain visual acuity in long-term follow-up [ 6 ]. However, these studies require strict adherence to the treatment protocols of each clinical trial during the therapeutic process. Current treatment regimens for RVO-ME patients include individualized modalities, such as 1 + PRN (Pro re nata) [ 7 ], 3 + PRN [ 8 ], or a combination of treat-and-extend (TAE) [ 9 ]. Approximately one-quarter of RVO-ME patients treated with anti-VEGF therapy are lost to follow-up (LTFU) in real-world studies [ 10 ]. The current status of LTFU after anti-VEGF therapy in RVO-ME patients has rarely been reported in China. Therefore, this study aims to analyze the lost visits of RVO-ME patients who received at least one intravitreal injection of anti-VEGF therapy and had LTFU for more than six months in our department [ 11 – 14 ]. This study indents to discuss LTFU causes and prognosis and to provide a basis for strengthening the standardized management of RVO-ME patients after treatment, thereby reducing the LTFU rate minimizing recurrence, and improving the quality of patients' lives. Method This was a retrospective study of patients who were LTFU for more than six months after receiving intravitreal anti-VEGF injections for RVO-ME. Patients were diagnosed with RVO-ME at the Ophthalmology Department of the Second Affiliated Hospital of Chongqing Medical University between January 2019 and August 2022. The study was approved by the Institutional Ethics Committee of the Second Hospital of Chongqing Medical University, following the ethical principles of the Declaration of Helsinki. The informed consent was obtained and signed by the patients. Exclusion criteria included glaucoma, age-related macular degeneration, diabetic retinopathy, previous intravitreal injections of hormonal or anti-VEGF drugs, laser photocoagulation, or inability to cooperate with treatment. Patients' age, sex, usual residence, type of anti-VEGF agent, number of injections before LTFU, and primary disease were collected by reviewing their electronic hospital files. Best corrected visual acuity (BCVA) and CMT were collected from revisited patients at baseline, the last time before LTFU, and the first time after the return visit. Months of treatment before LTFU and months of LTFU were collected. Patients who did not return to the clinic for follow-up more than six months after surgery were classified as the continued LTFU group; patients who returned more than six months after surgery were classified as the revisited group. All patients were questioned by telephone to inquire regarding the primary reasons for LTFU: no improvement in vision, treatment elsewhere, transport inconvenience, financial reasons, 2019-nCov epidemic, and unwillingness, with single-choice questions. The data were statistically analyzed using SPSS 26.0. Fractional visual acuity was converted to a logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Normally distributed data were expressed as mean ± standard deviation (SD). An independent sample t -test was used to compare the two groups. Non-normally distributed data were expressed as M (P25 to P75) using the Mann-Whitney U test. The Wilcoxon test was used for paired comparisons of two samples, while the Friedman M test was used for paired comparisons of multiple samples. Count data were expressed as composition ratio (%). The chi-square test was used to compare groups, while Fisher's exact test was used if the theoretical frequency was T < 1 or n < 40. A stepwise linear regression analysis was performed to assess the factors influencing visual acuity outcomes after LTFU. P -values < 0.05 were considered statistically significant. Result This study included 125 affected eyes; 63 (50.4%) were male, and 62 (49.6%) were female, with a mean age of 62.4 ± 11.7 years. Among these, 103 (82.4%) patients remained LTFU, while 22 (17.6%) patients revisited. A total of 73 (58.4%) patients had hypertension, and 10 (8%) had diabetes mellitus. Moreover, 102 (81.6%) eyes were treated with ranibizumab, 14 (11.2%) with conbercept, and 9 (7.2%) with aflibercept. The distance from the hospital was less than 10 km in 36 (28.8%) patients, more than 20 km in 76 (60.8%) patients, and 10–20 km in the remaining 13 (10.4%) patients. Before the LTFU, 72 (57.6%) patients had three or more anti-VEGF injections, 33 (26.4%) patients had LTFU after one treatment, and 20 (16.0%) patients had only two anti-VEGF therapies (Table 1 ). The number of injections before LTFU was a risk factor for lost visits in the multifactorial logistic regression analysis ( P < 0.05, Table 2 ). Table 1 Demographic characteristics Demographic characteristics Continued LTFU (n = 103) Revisited (n = 22) Total (n = 125) P -value Age (years), mean (SD) 62.6 ± 11.7 61.4 ± 11.8 62.4 ± 11.7 0.67 Gender (%) 0.967# Male 52 (50.5) 11 (50.0) 63 (50.4%) Female 51 (49.5) 11 (50.0) 62 (49.6%) Hypertension (%) 56 (54.4) 17 (77.3) 73 (58.4) 0.058* Anti-VEGF therapy (%) 0.349* Aflibercept 7 (6.8) 2 (9.1) 9 (7.2) Conbercept 10 (9.7) 4 (18.2) 14 (11.2) Ranibizumab 86 (83.5) 16 (72.7) 102 (81.6) Distance (%) 0.165* 20 km 66 (64.1) 10 (45.5) 76 (60.8) Injections before being LTFU (%) < 0.05* 1 32 (31.1) 1 (4.5) 33 (26.4) 2 19 (18.4) 1 (4.5) 20 (16.0) ≥ 3 52 (50.5) 20 (90.9) 72 (57.6) # Chi-square test; * Fisher's exact test. VEGF, vascular endothelial growth factor; LTFU, lost to follow-up. Table 2 Multifactorial logistic regression analysis affecting missed visits in patients with RVO-ME Influencing Factors β SE Wald \({{x}}^{2}\) OR 95% CI P -value One injection before LTFU 2.344 1.059 4.895 10.420 1.307 ~ 83.093 0.027 We conducted telephone follow-ups for 125 patients who failed to seek medical care within the prescribed time frame. This study revealed that 43 patients (34.4%) reported no improvement in vision, 28 (22.4%) did not seek medical care due to transport inconvenience, 16 (12.8%) said they were unwilling to see the doctor, 15 (12.0%) had chosen to seek medical care elsewhere, 12 (9.6%) failed to visit the clinic in time due to the 2019-nCov epidemic, and 11 (8.8%) indicated that they could not afford it due to financial reasons (Fig. 1 ). Table 3 Distribution of the number of injections in patients who LTFU Reasons 1 (n = 33) 2 (n = 20) ≥ 3 (n = 72) P -value No improvement in vision 5 (11.6) 7 (6.3) 31 (72.1) 0.04* Treatment elsewhere 4 (26.7) 3 (20.0) 8 (53.3) Transport inconvenience 7 (25.0) 4 (14.3) 17 (60.7) Financial reasons 8 (72.7) 1 (9.1) 2 (18.2) 2019-ncov epidemic 3 (25.0) 2 (16.7) 7 (58.3) Unwillingness 6 (37.5) 3 (18.8) 7 (43.8) Table 4 Distribution of distance of patients who LTFU Reasons ༜10 km (n = 36) 10–20 km (n = 13) ༞20 km (n = 76) P -value No improvement in vision 22 (51.2) 5 (11.6) 16 (37.2) < 0.001 Treatment elsewhere 3 (20.0) 3 (20.0) 9 (60.0) Transport inconvenience 0 (0.0) 1 (3.6) 27 (96.4) Financial reasons 2 (18.2) 1 (9.1) 8 (72.7) 2019-ncov epidemic 1 (8.3) 2 (16.7) 9 (75.0) Unwillingness 8 (50.0) 1 (6.3) 7 (43.8) Table 5 LogMAR and CMT characteristics before and after LTFU in the revisit group Initial visit Before LTFU Revisited Chi-square P- value LogMAR 0.9 (0.5 ~ 1.3) 0.4 (0.2 ~ 0.9) a 0.7 (0.2 ~ 1.6) 7.487 0.024 CMT 579.5 (367.5 ~ 781.3) 239.5 (181.9 ~ 357.5) a 228.5 (188.6 ~ 423.4) a 16.575 < 0.001 a P < 0.05 compared to the initial visit. After three or more injections, 72.1 patients were LTFU due to "no improvement in vision." After one injection, 72.7% of patients did not visit due to "financial reasons" (Table 3 ). In addition to the 96.4% of patients who were LTFU due to "transport inconvenience," 75.0% of patients were not followed up due to the "2019-nCov epidemic" at a distance of more than 20 km from the hospital (Table 4 ). Table 5 and Fig. 2 illustrate the analysis of logMAR and CMT at the initial visit, before LTFU, and revisited 22 patients with the revisit. LogMAR was significantly lower before the LTFU initial at the first visit ( P 0.05). The median value of CMT at the initial visit (P25 ~ P75) was 579.5 (367.5 ~ 781.3) µm, and the difference was statistically significant compared to the CMT before LTFU and after the return visit ( P 0.05). Table 6 LogMAR and CMT versus baseline after revisiting for uncomplicated patients Initial visit Revisited P -value logMAR 0.8 (0.6 ~ 1.3) 0.2 (0.1 ~ 1.2) 0.011 CMT 513.0 (366.0 ~ 728.9) 198.0 (173.0 ~ 218.0) 0.003 Table 7 The factors influencing the best corrected visual acuity at revisit Baseline Characteristics P β 95% Confidence Intervals Age 0.539 Gender 0.269 Hypertension 0.654 BCVA at Initial visit (logMAR) < 0.001* 1.367 0.916–1.818 BCVA before being LTFU (logMAR) 0.976 CMT at the Initial Visit 0.047* -0.001 -0.002–0.000 CMT before being LTFU < 0.001* 0.001 0.001–0.002 CMT at a return visit 0.013* 0.001 0.000–0.002 Injections before being LTFU 0.503 LTFU length 0.641 Among the 22 patients who were revisited, 11 had complications, including four (18.2%) with epiretinal membranes, two (9.1%) with macular edema, three (13.6%) with macular membrane and macular edema, one (4.5%) with vitreous blood, and one with neovascular glaucoma. The logMAR and CMT of 11 patients without complications were compared to the baseline after the return visit. The visual acuity improved to 0.2 (0.1 ~ 1.2; P < 0.05), and the CMT decreased to 198.0 (173.0 ~ 218.0 µm; P < 0.05; Table 6 ) after the return visit. The age and sex of patients, hypertension status, injection times before LTFU, treatment time before LTFU, logMAR and CMT at the initial visit, logMAR and CMT before LTFU, logMAR, and CMT after return visit, and LTFU months were included in the stepwise regression analysis model. The results exhibited that logMAR at the initial visit ( P < 0.001), CMT at the initial visit ( P < 0.05), CMT before LTFU ( P < 0.001), and CMT after the return visit ( P < 0.05) were all factors influencing logMAR at return visit (Table 7 ). Discussion RVO is the world's second most blinding retinal vascular disease after diabetic retinopathy, with a prevalence of approximately 0.77% [ 15 ]. VEGF factor plays an essential role in developing RVO, making the intravitreal injection of anti-VEGF drugs the first-line treatment for RVO-ME patients [ 16 ]. During the initial phase of anti-VEGF, most patients have a positive response, but some patients still need repeated treatment to block disease progression and achieve the stable vision. Patient compliance determines the frequency of treatment and follow-up. Anti-VEGF treatment improves visual acuity and anatomy at six and 12 months in RVO-ME patients [ 17 ]. At least six months of follow-up is required to determine treatment effects and adverse effects. This presents that LTFU in RVO-ME patients is an essential factor affecting their visual quality of RVO-ME. We frequently use a 3 + PRN regimen, combined with research practice [ 11 – 14 ], and define RVO-ME patients who do not attend outpatient follow-up for more than six months as lost to follow-up. This study analyzed the causes of lost visits to LTFU after intravitreal injection of anti-VEGF for RVO-ME, as well as the effect of LTFU on the prognosis of RVO-ME patients who received intravitreal injection of anti-VEGF. Our study demonstrated that 49.2% of patients would LTFU after anti-VEGF treatment. Among 125 LTFU patients, 82.4% of RVO-ME patients did not return more than six months after the last injection, whereas only 17.6% of patients treated with intravitreal anti-VEGF injections returned more than six months after LTFU. Currently, irregular treatment of RVO patients has been reported in other countries. Kelkar et al. [ 18 ] retrospectively studied the compliance of patients with DME, AMD, and RVO in Indian society who received anti-VEGF therapy, presenting that 50% of the patients did not revisit the clinic for more than a year. Another research team published a retrospective cohort study [ 10 ], revealing that 25.4% of RVO-ME patients treated with intravitreal anti-VEGF injections developed LTFU in at least one of the five years after receiving intravitreal injections. The difference in the rate of loss to follow-up may be related to the local level of care, infrastructure, and patients' willingness to visit the clinic. In this study, the common causes of LTFU were "no improvement in vision" and "transport inconvenience." The number of injections before LTFU was a risk factor. This agrees with Kelkar et al. [ 18 ], who presented that the common causes of LTFU were "no improvement in vision" and "non-affordability." In contrast, most patients had LTFU after one injections, suggesting that the causes of LTFU are related to the number of injections patients receive. "Financial reasons" may be related to the patient’s inability to pay the high cost and refusal to continue treatment without significant improvement in visual acuity. However, Yang et al. [ 11 ] indicated "noncompliance" as the primary reason, which may be related to the inclusion of RVO patients with a mean age of 60.2 ± 7.2 years and poorer compliance in middle-aged and elderly people. A retrospective study by Gao et al. [ 10 ] indicated that race, age, type of RVO, and distance from the hospital were risk factors for LTFU. This differs from the present study’s results, probably due to ethnicity and sample size differences. There are various treatment options for RVO, such as 1 + PRN, 3 + PRN, and TAE. Regardless of the treatment option, treatment frequency is fundamental in the first year. The number of injections with the PRN regimen in RVO patients is approximately seven to eight in the first year [ 20 , 21 ]. Additionally, RVO treatment is complemented by follow-up, with approximately half of RVO patients requiring long-term treatment, particularly CRVO patients who may require more frequent follow-up visits [ 22 , 23 ]. However, patients who have received more than three injections frequently lose confidence in continuing treatment due to "no improvement in vision." In contrast, others choose LTFU after one treatment for "financial reasons," perhaps because their vision does not meet the requirements for special drug medical insurance or their families cannot afford the high cost of treatment, thus abandoning the treatment. Some elderly patients refuse to return to the hospital due to their personalities or are non-accompanied by family members. Distance is also the reason for LTFU for some patients. Some patients do not visit the hospital within the prescribed time or visit other hospitals because they live in remote towns or are more than 20 km away from the hospital due to the need for frequent follow-up visits. These reasons can lead to treatment interruptions and missed optimal treatment time for RVO-ME patients, posing a significant challenge to standardizing treatment for RVO-ME patients. One study [ 19 ] exhibited that 70% of RVO patients had deteriorating vision in the affected eye after long-term LTFU recovery, with only 33% recovering to pre-LTFU levels after restarting anti-VEGF therapy. Another study reported [ 11 ] that CMT was measured in the affected eyes of RVO patients at a follow-up visit after treatment interruption. All eyes had more significant ME than baseline. Consistent with our analysis of the prognosis of RVO patients who returned after LTFU, the current study confirms that the BCVA and CMT of the affected eye at the time of the return visit were worse in RVO patients after LTFU compared to before LTFU. This also demonstrates the importance of regular follow-up and continuous treatment to recover visual acuity and anatomical form. We discovered that 50% of the revisiters had no complications, with the analysis presenting an improvement in their BCVA and CMT than the initial treatment, the CMT of these patients being less than 250 µm. The visual outcome and anatomical morphology improvement may have prevented this patient group from continuing to LTFU, but 50% of the patients still had varying degrees of complications, resulting in vision deterioration and return to the clinic. Our analysis of the best visual acuity at the return visit after LTFU revealed that logMAR at the initial visit, CMT at the initial visit, CMT before the LTFU, and CMT after the LTFU were all factors influencing the visual acuity at the return visit. A retrospective study discovered [ 24 ] that untreated BCVA was a predictor of visual quality in CRVO patients receiving anti-VEGF therapy. Sen et al. [ 25 ] similarly confirmed that baseline BCVA and CMT affect final BCVA after anti-VEGF therapy, with baseline BCVA being the known predictor of the final visual outcome. Similarly, the results of a retrospective study conducted by Salabati et al. [ 19 ] confirmed the above. However, Yang et al. [ 11 ] demonstrate a correlation between visual prognosis and LTFU length. Pre-LTFU and post-return CMT affect visual acuity at the final return visit has not been explored. This is the first to reveal that four major factors, baseline visual acuity and CMT, pre-LTFU, and post-LTFU CMT, can affect visual acuity at the return visit after RVO-ME patients receive anti-VEGF treatment for LTFU. It provides a new theoretical basis for regular follow-up and on-demand anti-VEGF treatment of ME in RVO-ME patients and strong evidence that reducing CMT in RVO-ME patients can improve visual quality. Earlier detection, better diagnosis, faster treatment, and regular follow-up should be carried out to avoid further deterioration of visual quality and missing the best treatment time to save vision in RVO-ME patients. Our study has several limitations. First, this was a retrospective study which might be subject to selection bias. Since we could only collect information on patients who visited our hospital instead of all hospital visits in our area, some patients might have visited other hospitals for personal reasons. Consequently, we lost the follow-up management of this patient group. Second, this was a single-center clinical study with a small included sample size and a lack of support from the results of multicenter clinical studies, limiting our further analysis of the follow-up treatment of patients who returned for a second visit. Therefore, we can combine multicenter studies while expanding the sample size to improve the study results further in the future. Third, we request patients to choose only one reason for LTFU, while the telephone questioning style is subjective; therefore, patients avoid the question and prefer a more conservative response. Conclusion In conclusion, our study discovered that the primary reasons for LTFU in most RVO-ME patients receiving anti-VEGF therapy were no improvement in visual acuity and transport inconvenience, with effective patient management and follow-up improving the motivation for regular outpatient follow-up and treatment in RVO-ME patients. Our findings reveal for the first time that visual acuity at the return visit is influenced by four major factors, baseline visual acuity, baseline CMT, pre-LTFU CMT, and post-return CMT. Additionally, the number of injections before LTFU was a risk factor for LTFU. Therefore, patients must pay more attention to the visual quality and ocular anatomical hazards caused by LTFU. In the future, more comprehensive, multicenter clinical data are expected to study the hazards of LTFU on RVO-ME to identify the best time to intervene, enhance outpatient follow-up, and protect the visual quality of patients. Conclusion In conclusion, our study found that the main reasons for LTFU in most RVO-ME patients receiving anti-VEGF therapy were no improvement in visual acuity and transport inconvenience, with effective patient management as well as follow-up improving the motivation for regular outpatient follow-up and treatment in RVO-ME patients. Our findings reveal for the first time that visual acuity at the return visit is influenced by four major factors: baseline visual acuity, baseline CMT, pre-LTFU CMT, and post-return CMT. In addition, the number of injections before LTFU was a risk factor for LTFU. Therefore, patients need to pay more attention to the visual quality and ocular anatomical hazards caused by LTFU. In the future, more comprehensive, multicenter clinical data are expected to study the hazards of LTFU on RVO-ME, in order to find the best time to intervene, enhance outpatient follow-up, and protect the visual quality of patients. Abbreviations ME:macular edema;RVO:retinal vein occlusion;VEGF:anti-vascular endothelial growth factor therapy;LTFU:lost to follow-up;BCVA:best corrected visual acuity;CMT:central macular thickness;PRN:Pro re nata;TAE:treat-and-extend;logMAR:logarithm of the minimumangle of resolution;SD:standard deviation. Declarations Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the ethics committee at Second Affiliated Hospital of Chongqing Medical University and conducted in accordance with the principles of the Helsinki Declaration. Written informed consent was obtained from all patients. Consent for publication Not applicable. Competing interests None of the authors have any competing interests to disclose. Funding This work was supported by the Project of Chongqing Health and Family Planning Commission (ZY20162085). Authors’ contributions HXY contributed to study design, statistical analyze, data acquisition and manuscript preparation; ZMM, LJT and WX contributed to literature research and clinical studies; ZMM contributed to manuscript review; ZZ was the guarantor of integrity of the entire study and contributed to study concepts, and data analyze; The final version of the manuscript has been read and approved by all authors. Acknowledgements We thank all participants in this study. References Kohli P, Patel BC. Macular Edema. StatPearls. Treasure Island (FL):StatPearls Publishing;2022. Daruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, Rothschild PR, Omri S, Gélizé E, Jonet L, Delaunay K, De Kozak Y, Berdugo M, Zhao M, Crisanti P, Behar-Cohen F. Mechanisms of macular edema: Beyond the surface. Prog Retin Eye Res. 2018;63:20–68. Iijima H. Mechanisms of vision loss in eyes with macular edema associated with retinal vein occlusion. Jpn J Ophthalmol. 2018;62(3):265–73. 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Outcomes of Eyes With Diabetic Macular Edema That Are Lost to Follow-up After Anti-Vascular Endothelial Growth Factor Therapy. Am J Ophthalmol. 2022;233:1–7. Song P, Xu Y, Zha M, Zhang Y, Rudan I. Global epidemiology of retinal vein occlusion: a systematic review and meta-analyze of prevalence, incidence, and risk factors. J Glob Health. 2019;9(1):010427. Schmidt-Erfurth U, Garcia-Arumi J, Gerendas BS, Midena E, Sivaprasad S, Tadayoni R, Wolf S, Loewenstein A. Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2019;242(3):123–62. Shalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020;7(7):CD009510. Kelkar A, Webers C, Shetty R, Kelkar J, Labhsetwar N, Pandit A, Malode M, Tidke S. Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion, age-related macular degeneration, and diabetic macular edema. Indian J Ophthalmol. 2020;68(10):2143–7. Salabati M, Mahmoudzadeh R, Wong JC, Patel D, Patel SN, Obeid A, Sivalingam A, Vander JF, Garg SJ, Ho AC, Regillo CD, Hsu J. Outcomes of eyes with retinal vein occlusion that are lost to follow-up after antivascular endothelial growth factor therapy. Br J Ophthalmol. 2022;106(12):1742–7. Ogura Y, Roider J, Korobelnik J-F, Holz FG, Simader C, Schmidt-Erfurth U, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, et al. Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study. Am J Ophthalmol. 2014;158:1032–1038e2. Park DG, Jeong WJ, Park JM, Kim JY, Ji YS, Sagong M. Prospective trial of treat-and-extend regimen with aflibercept for branch retinal vein occlusion: 1-year results of the PLATON trial. Graefes Arch Clin Exp Ophthalmol. 2021;259(10):2879–86. Terao R, Fujino R, Ahmed T. Risk Factors and Treatment Strategy for Retinal Vascular Occlusive Diseases. J Clin Med. 2022;11(21):6340. Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012;119(4):802–9. Brogan K, Precup M, Rodger A, Young D, Gilmour DF. Pre-treatment clinical features in central retinal vein occlusion that predict visual outcome following intravitreal ranibizumab. BMC Ophthalmol. 2018;18(1):37. Sen P, Gurudas S, Ramu J, Patrao N, Chandra S, Rasheed R, Nicholson L, Peto T, Sivaprasad S, Hykin P. Predictors of Visual Acuity Outcomes after Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion. Ophthalmol Retina. 2021;5(11):1115–24. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Jun, 2023 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Major revision 18 Apr, 2023 Reviews received at journal 17 Apr, 2023 Reviews received at journal 08 Apr, 2023 Reviewers agreed at journal 31 Mar, 2023 Reviewers agreed at journal 29 Mar, 2023 Reviewers invited by journal 29 Mar, 2023 Editor assigned by journal 18 Mar, 2023 Editor invited by journal 27 Feb, 2023 Submission checks completed at journal 27 Feb, 2023 First submitted to journal 20 Feb, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2608586","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":179246058,"identity":"db018bd8-6466-4ba7-b071-5dc4a943fa98","order_by":0,"name":"Xiaoying Huang","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoying","middleName":"","lastName":"Huang","suffix":""},{"id":179246059,"identity":"3316fddf-2231-4d94-abce-4cda047d8a89","order_by":1,"name":"Minming Zheng","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Minming","middleName":"","lastName":"Zheng","suffix":""},{"id":179246060,"identity":"8481dbe8-f987-4ffd-b1c1-c12b4eab2b82","order_by":2,"name":"Jiatao Lu","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiatao","middleName":"","lastName":"Lu","suffix":""},{"id":179246061,"identity":"11dc28c6-3ba9-4e16-85ca-fce8e1333b4b","order_by":3,"name":"Xi Wang","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Wang","suffix":""},{"id":179246062,"identity":"f40f453c-7ea7-4797-b6ce-24223e455fce","order_by":4,"name":"Zheng Zheng","email":"data:image/png;base64,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","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2023-02-20 15:29:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2608586/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2608586/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-023-03018-9","type":"published","date":"2023-06-12T21:11:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":33707094,"identity":"51b67566-0a7a-44a7-86de-ad859eabea02","added_by":"auto","created_at":"2023-03-02 20:02:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":176572,"visible":true,"origin":"","legend":"\u003cp\u003eReasons for LTFU of RVO-ME\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-2608586/v1/553028868d15a86bdf04a00e.png"},{"id":33706334,"identity":"19078c90-284c-41a9-9af8-ca06fd3e1f4e","added_by":"auto","created_at":"2023-03-02 19:54:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":299823,"visible":true,"origin":"","legend":"\u003cp\u003eLogMAR and CMT change curves before and after LTFU in the revisit group\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-2608586/v1/7011ebf3fb164bb7f5c45115.png"},{"id":44731661,"identity":"61fff640-cd7f-4338-ac93-223f63cbdba3","added_by":"auto","created_at":"2023-10-16 21:46:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":689504,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2608586/v1/2c0fc4ea-7fce-45c5-ad82-0f204c942b56.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRetinal Vein Occlusion (RVO) is a secondary retinal vascular disease that commonly causes visual loss. Local ischemia and hypoxia in the retina cause an increase in the concentration of cytokines, including vascular endothelial growth factor (VEGF) and inflammatory factors, resulting in fluid accumulation in the inner and lower layers of the retina by disrupting the blood-retinal barrier to promote neovascularization and macular edema (ME) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. ME is the major cause of poor vision in RVO, while intravitreal injections of anti-VEGF drugs can effectively reduce intraocular VEGF concentrations, thereby decreasing central macular thickness (CMT) and ME [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The BRAVO and CRUISE trials are two large prospective randomized controlled trials demonstrating the effectiveness of intravitreal injections of ranibizumab in BRVO-ME and CRVO-ME [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Studies have demonstrated that RVO, especially CRVO, may require more frequent follow-up in the second year of treatment to maintain visual acuity in long-term follow-up [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, these studies require strict adherence to the treatment protocols of each clinical trial during the therapeutic process. Current treatment regimens for RVO-ME patients include individualized modalities, such as 1\u0026thinsp;+\u0026thinsp;PRN (Pro re nata) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], 3\u0026thinsp;+\u0026thinsp;PRN [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], or a combination of treat-and-extend (TAE) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Approximately one-quarter of RVO-ME patients treated with anti-VEGF therapy are lost to follow-up (LTFU) in real-world studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The current status of LTFU after anti-VEGF therapy in RVO-ME patients has rarely been reported in China. Therefore, this study aims to analyze the lost visits of RVO-ME patients who received at least one intravitreal injection of anti-VEGF therapy and had LTFU for more than six months in our department [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This study indents to discuss LTFU causes and prognosis and to provide a basis for strengthening the standardized management of RVO-ME patients after treatment, thereby reducing the LTFU rate minimizing recurrence, and improving the quality of patients' lives.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThis was a retrospective study of patients who were LTFU for more than six months after receiving intravitreal anti-VEGF injections for RVO-ME. Patients were diagnosed with RVO-ME at the Ophthalmology Department of the Second Affiliated Hospital of Chongqing Medical University between January 2019 and August 2022. The study was approved by the Institutional Ethics Committee of the Second Hospital of Chongqing Medical University, following the ethical principles of the Declaration of Helsinki. The informed consent was obtained and signed by the patients.\u003c/p\u003e \u003cp\u003eExclusion criteria included glaucoma, age-related macular degeneration, diabetic retinopathy, previous intravitreal injections of hormonal or anti-VEGF drugs, laser photocoagulation, or inability to cooperate with treatment. Patients' age, sex, usual residence, type of anti-VEGF agent, number of injections before LTFU, and primary disease were collected by reviewing their electronic hospital files. Best corrected visual acuity (BCVA) and CMT were collected from revisited patients at baseline, the last time before LTFU, and the first time after the return visit. Months of treatment before LTFU and months of LTFU were collected. Patients who did not return to the clinic for follow-up more than six months after surgery were classified as the continued LTFU group; patients who returned more than six months after surgery were classified as the revisited group. All patients were questioned by telephone to inquire regarding the primary reasons for LTFU: no improvement in vision, treatment elsewhere, transport inconvenience, financial reasons, 2019-nCov epidemic, and unwillingness, with single-choice questions.\u003c/p\u003e \u003cp\u003eThe data were statistically analyzed using SPSS 26.0. Fractional visual acuity was converted to a logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Normally distributed data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). An independent sample \u003cem\u003et\u003c/em\u003e-test was used to compare the two groups. Non-normally distributed data were expressed as M (P25 to P75) using the Mann-Whitney U test. The Wilcoxon test was used for paired comparisons of two samples, while the Friedman M test was used for paired comparisons of multiple samples. Count data were expressed as composition ratio (%). The chi-square test was used to compare groups, while Fisher's exact test was used if the theoretical frequency was T\u0026thinsp;\u0026lt;\u0026thinsp;1 or n\u0026thinsp;\u0026lt;\u0026thinsp;40. A stepwise linear regression analysis was performed to assess the factors influencing visual acuity outcomes after LTFU. \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eThis study included 125 affected eyes; 63 (50.4%) were male, and 62 (49.6%) were female, with a mean age of 62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7 years. Among these, 103 (82.4%) patients remained LTFU, while 22 (17.6%) patients revisited. A total of 73 (58.4%) patients had hypertension, and 10 (8%) had diabetes mellitus. Moreover, 102 (81.6%) eyes were treated with ranibizumab, 14 (11.2%) with conbercept, and 9 (7.2%) with aflibercept. The distance from the hospital was less than 10 km in 36 (28.8%) patients, more than 20 km in 76 (60.8%) patients, and 10\u0026ndash;20 km in the remaining 13 (10.4%) patients. Before the LTFU, 72 (57.6%) patients had three or more anti-VEGF injections, 33 (26.4%) patients had LTFU after one treatment, and 20 (16.0%) patients had only two anti-VEGF therapies (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The number of injections before LTFU was a risk factor for lost visits in the multifactorial logistic regression analysis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemographic characteristics\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDemographic characteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eContinued LTFU (n\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRevisited (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;125)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\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\u003eAge (years), mean (SD)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e61.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.67\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGender (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.967#\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52 (50.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63 (50.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51 (49.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62 (49.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56 (54.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (77.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73 (58.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.058*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnti-VEGF therapy (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.349*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAflibercept\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (6.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (7.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConbercept\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (9.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14 (11.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRanibizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e86 (83.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (72.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e102 (81.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDistance (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.165*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;10 km\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36 (28.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u0026ndash;20 km\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (10.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (10.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;20 km\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66 (64.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76 (60.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInjections before being LTFU (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32 (31.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33 (26.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (18.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (16.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52 (50.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (90.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72 (57.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e# Chi-square test;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e* Fisher's exact test.\u003c/p\u003e\n\u003cp\u003eVEGF, vascular endothelial growth factor; LTFU, lost to follow-up.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMultifactorial logistic regression analysis affecting missed visits in patients with RVO-ME\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eInfluencing Factors\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026beta;\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWald\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({{x}}^{2}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\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\u003eOne injection before LTFU\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.344\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.059\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.895\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.420\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.307\u0026thinsp;~\u0026thinsp;83.093\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.027\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\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe conducted telephone follow-ups for 125 patients who failed to seek medical care within the prescribed time frame. This study revealed that 43 patients (34.4%) reported no improvement in vision, 28 (22.4%) did not seek medical care due to transport inconvenience, 16 (12.8%) said they were unwilling to see the doctor, 15 (12.0%) had chosen to seek medical care elsewhere, 12 (9.6%) failed to visit the clinic in time due to the 2019-nCov epidemic, and 11 (8.8%) indicated that they could not afford it due to financial reasons (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDistribution of the number of injections in patients who LTFU\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eReasons\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1 (n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2 (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;3 (n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\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\u003eNo improvement in vision\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (11.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (6.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31 (72.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"6\" align=\"left\"\u003e\n\u003cp\u003e0.04*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTreatment elsewhere\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (26.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (53.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTransport inconvenience\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17 (60.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFinancial reasons\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (72.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019-ncov epidemic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (58.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnwillingness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6 (37.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (18.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (43.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDistribution of distance of patients who LTFU\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eReasons\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e༜10 km (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e10\u0026ndash;20 km (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e༞20 km (n\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\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\u003eNo improvement in vision\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22 (51.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (11.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16 (37.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"6\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTreatment elsewhere\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9 (60.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTransport inconvenience\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (3.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e27 (96.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFinancial reasons\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (72.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019-ncov epidemic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9 (75.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnwillingness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (6.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (43.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogMAR and CMT characteristics before and after LTFU in the revisit group\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eInitial visit\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBefore LTFU\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRevisited\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eChi-square\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\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\u003eLogMAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9 (0.5\u0026thinsp;~\u0026thinsp;1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.4 (0.2\u0026thinsp;~\u0026thinsp;0.9) a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7 (0.2\u0026thinsp;~\u0026thinsp;1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.487\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.024\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCMT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e579.5 (367.5\u0026thinsp;~\u0026thinsp;781.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e239.5 (181.9\u0026thinsp;~\u0026thinsp;357.5) a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e228.5 (188.6\u0026thinsp;~\u0026thinsp;423.4) a\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.575\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt; 0.001\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\u003ea \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 compared to the initial visit.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter three or more injections, 72.1 patients were LTFU due to \"no improvement in vision.\" After one injection, 72.7% of patients did not visit due to \"financial reasons\" (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). In addition to the 96.4% of patients who were LTFU due to \"transport inconvenience,\" 75.0% of patients were not followed up due to the \"2019-nCov epidemic\" at a distance of more than 20 km from the hospital (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e illustrate the analysis of logMAR and CMT at the initial visit, before LTFU, and revisited 22 patients with the revisit. LogMAR was significantly lower before the LTFU initial at the first visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while there was no difference after the return visit compared to the initial visit and before the LTFU (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The median value of CMT at the initial visit (P25\u0026thinsp;~\u0026thinsp;P75) was 579.5 (367.5\u0026thinsp;~\u0026thinsp;781.3) \u0026micro;m, and the difference was statistically significant compared to the CMT before LTFU and after the return visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but there was no statistical difference between the CMT before LTFU and after return visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab6\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogMAR and CMT versus baseline after revisiting for uncomplicated patients\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eInitial visit\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRevisited\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\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\u003elogMAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.8 (0.6\u0026thinsp;~\u0026thinsp;1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.2 (0.1\u0026thinsp;~\u0026thinsp;1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.011\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCMT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e513.0 (366.0\u0026thinsp;~\u0026thinsp;728.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e198.0 (173.0\u0026thinsp;~\u0026thinsp;218.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab7\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe factors influencing the best corrected visual acuity at revisit\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline Characteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026beta;\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% Confidence Intervals\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\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.539\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.269\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.654\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBCVA at Initial visit (logMAR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.367\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.916\u0026ndash;1.818\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBCVA before being LTFU (logMAR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.976\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCMT at the Initial Visit\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.047*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.002\u0026ndash;0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCMT before being LTFU\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u0026ndash;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCMT at a return visit\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.013*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u0026ndash;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInjections before being LTFU\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.503\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLTFU length\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.641\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAmong the 22 patients who were revisited, 11 had complications, including four (18.2%) with epiretinal membranes, two (9.1%) with macular edema, three (13.6%) with macular membrane and macular edema, one (4.5%) with vitreous blood, and one with neovascular glaucoma. The logMAR and CMT of 11 patients without complications were compared to the baseline after the return visit. The visual acuity improved to 0.2 (0.1\u0026thinsp;~\u0026thinsp;1.2; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and the CMT decreased to 198.0 (173.0\u0026thinsp;~\u0026thinsp;218.0 \u0026micro;m; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e) after the return visit.\u003c/p\u003e\n\u003cp\u003eThe age and sex of patients, hypertension status, injection times before LTFU, treatment time before LTFU, logMAR and CMT at the initial visit, logMAR and CMT before LTFU, logMAR, and CMT after return visit, and LTFU months were included in the stepwise regression analysis model. The results exhibited that logMAR at the initial visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), CMT at the initial visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), CMT before LTFU (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and CMT after the return visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were all factors influencing logMAR at return visit (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRVO is the world's second most blinding retinal vascular disease after diabetic retinopathy, with a prevalence of approximately 0.77% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. VEGF factor plays an essential role in developing RVO, making the intravitreal injection of anti-VEGF drugs the first-line treatment for RVO-ME patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. During the initial phase of anti-VEGF, most patients have a positive response, but some patients still need repeated treatment to block disease progression and achieve the stable vision. Patient compliance determines the frequency of treatment and follow-up. Anti-VEGF treatment improves visual acuity and anatomy at six and 12 months in RVO-ME patients [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. At least six months of follow-up is required to determine treatment effects and adverse effects. This presents that LTFU in RVO-ME patients is an essential factor affecting their visual quality of RVO-ME. We frequently use a 3\u0026thinsp;+\u0026thinsp;PRN regimen, combined with research practice [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and define RVO-ME patients who do not attend outpatient follow-up for more than six months as lost to follow-up.\u003c/p\u003e \u003cp\u003eThis study analyzed the causes of lost visits to LTFU after intravitreal injection of anti-VEGF for RVO-ME, as well as the effect of LTFU on the prognosis of RVO-ME patients who received intravitreal injection of anti-VEGF. Our study demonstrated that 49.2% of patients would LTFU after anti-VEGF treatment. Among 125 LTFU patients, 82.4% of RVO-ME patients did not return more than six months after the last injection, whereas only 17.6% of patients treated with intravitreal anti-VEGF injections returned more than six months after LTFU. Currently, irregular treatment of RVO patients has been reported in other countries. Kelkar et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] retrospectively studied the compliance of patients with DME, AMD, and RVO in Indian society who received anti-VEGF therapy, presenting that 50% of the patients did not revisit the clinic for more than a year. Another research team published a retrospective cohort study [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], revealing that 25.4% of RVO-ME patients treated with intravitreal anti-VEGF injections developed LTFU in at least one of the five years after receiving intravitreal injections. The difference in the rate of loss to follow-up may be related to the local level of care, infrastructure, and patients' willingness to visit the clinic.\u003c/p\u003e \u003cp\u003eIn this study, the common causes of LTFU were \"no improvement in vision\" and \"transport inconvenience.\" The number of injections before LTFU was a risk factor. This agrees with Kelkar et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], who presented that the common causes of LTFU were \"no improvement in vision\" and \"non-affordability.\" In contrast, most patients had LTFU after one injections, suggesting that the causes of LTFU are related to the number of injections patients receive. \"Financial reasons\" may be related to the patient\u0026rsquo;s inability to pay the high cost and refusal to continue treatment without significant improvement in visual acuity. However, Yang et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] indicated \"noncompliance\" as the primary reason, which may be related to the inclusion of RVO patients with a mean age of 60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 years and poorer compliance in middle-aged and elderly people. A retrospective study by Gao et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] indicated that race, age, type of RVO, and distance from the hospital were risk factors for LTFU. This differs from the present study\u0026rsquo;s results, probably due to ethnicity and sample size differences.\u003c/p\u003e \u003cp\u003eThere are various treatment options for RVO, such as 1\u0026thinsp;+\u0026thinsp;PRN, 3\u0026thinsp;+\u0026thinsp;PRN, and TAE. Regardless of the treatment option, treatment frequency is fundamental in the first year. The number of injections with the PRN regimen in RVO patients is approximately seven to eight in the first year [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, RVO treatment is complemented by follow-up, with approximately half of RVO patients requiring long-term treatment, particularly CRVO patients who may require more frequent follow-up visits [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, patients who have received more than three injections frequently lose confidence in continuing treatment due to \"no improvement in vision.\" In contrast, others choose LTFU after one treatment for \"financial reasons,\" perhaps because their vision does not meet the requirements for special drug medical insurance or their families cannot afford the high cost of treatment, thus abandoning the treatment. Some elderly patients refuse to return to the hospital due to their personalities or are non-accompanied by family members. Distance is also the reason for LTFU for some patients. Some patients do not visit the hospital within the prescribed time or visit other hospitals because they live in remote towns or are more than 20 km away from the hospital due to the need for frequent follow-up visits. These reasons can lead to treatment interruptions and missed optimal treatment time for RVO-ME patients, posing a significant challenge to standardizing treatment for RVO-ME patients.\u003c/p\u003e \u003cp\u003eOne study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] exhibited that 70% of RVO patients had deteriorating vision in the affected eye after long-term LTFU recovery, with only 33% recovering to pre-LTFU levels after restarting anti-VEGF therapy. Another study reported [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] that CMT was measured in the affected eyes of RVO patients at a follow-up visit after treatment interruption. All eyes had more significant ME than baseline. Consistent with our analysis of the prognosis of RVO patients who returned after LTFU, the current study confirms that the BCVA and CMT of the affected eye at the time of the return visit were worse in RVO patients after LTFU compared to before LTFU. This also demonstrates the importance of regular follow-up and continuous treatment to recover visual acuity and anatomical form. We discovered that 50% of the revisiters had no complications, with the analysis presenting an improvement in their BCVA and CMT than the initial treatment, the CMT of these patients being less than 250 \u0026micro;m. The visual outcome and anatomical morphology improvement may have prevented this patient group from continuing to LTFU, but 50% of the patients still had varying degrees of complications, resulting in vision deterioration and return to the clinic. Our analysis of the best visual acuity at the return visit after LTFU revealed that logMAR at the initial visit, CMT at the initial visit, CMT before the LTFU, and CMT after the LTFU were all factors influencing the visual acuity at the return visit. A retrospective study discovered [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] that untreated BCVA was a predictor of visual quality in CRVO patients receiving anti-VEGF therapy. Sen et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] similarly confirmed that baseline BCVA and CMT affect final BCVA after anti-VEGF therapy, with baseline BCVA being the known predictor of the final visual outcome. Similarly, the results of a retrospective study conducted by Salabati et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] confirmed the above. However, Yang et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] demonstrate a correlation between visual prognosis and LTFU length. Pre-LTFU and post-return CMT affect visual acuity at the final return visit has not been explored. This is the first to reveal that four major factors, baseline visual acuity and CMT, pre-LTFU, and post-LTFU CMT, can affect visual acuity at the return visit after RVO-ME patients receive anti-VEGF treatment for LTFU. It provides a new theoretical basis for regular follow-up and on-demand anti-VEGF treatment of ME in RVO-ME patients and strong evidence that reducing CMT in RVO-ME patients can improve visual quality. Earlier detection, better diagnosis, faster treatment, and regular follow-up should be carried out to avoid further deterioration of visual quality and missing the best treatment time to save vision in RVO-ME patients. Our study has several limitations. First, this was a retrospective study which might be subject to selection bias. Since we could only collect information on patients who visited our hospital instead of all hospital visits in our area, some patients might have visited other hospitals for personal reasons. Consequently, we lost the follow-up management of this patient group. Second, this was a single-center clinical study with a small included sample size and a lack of support from the results of multicenter clinical studies, limiting our further analysis of the follow-up treatment of patients who returned for a second visit. Therefore, we can combine multicenter studies while expanding the sample size to improve the study results further in the future. Third, we request patients to choose only one reason for LTFU, while the telephone questioning style is subjective; therefore, patients avoid the question and prefer a more conservative response.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study discovered that the primary reasons for LTFU in most RVO-ME patients receiving anti-VEGF therapy were no improvement in visual acuity and transport inconvenience, with effective patient management and follow-up improving the motivation for regular outpatient follow-up and treatment in RVO-ME patients. Our findings reveal for the first time that visual acuity at the return visit is influenced by four major factors, baseline visual acuity, baseline CMT, pre-LTFU CMT, and post-return CMT. Additionally, the number of injections before LTFU was a risk factor for LTFU. Therefore, patients must pay more attention to the visual quality and ocular anatomical hazards caused by LTFU. In the future, more comprehensive, multicenter clinical data are expected to study the hazards of LTFU on RVO-ME to identify the best time to intervene, enhance outpatient follow-up, and protect the visual quality of patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study found that the main reasons for LTFU in most RVO-ME patients receiving anti-VEGF therapy were no improvement in visual acuity and transport inconvenience, with effective patient management as well as follow-up improving the motivation for regular outpatient follow-up and treatment in RVO-ME patients. Our findings reveal for the first time that visual acuity at the return visit is influenced by four major factors: baseline visual acuity, baseline CMT, pre-LTFU CMT, and post-return CMT. In addition, the number of injections before LTFU was a risk factor for LTFU. Therefore, patients need to pay more attention to the visual quality and ocular anatomical hazards caused by LTFU. In the future, more comprehensive, multicenter clinical data are expected to study the hazards of LTFU on RVO-ME, in order to find the best time to intervene, enhance outpatient follow-up, and protect the visual quality of patients.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eME:macular edema;RVO:retinal vein occlusion;VEGF:anti-vascular endothelial growth factor therapy;LTFU:lost to follow-up;BCVA:best corrected visual acuity;CMT:central macular thickness;PRN:Pro re nata;TAE:treat-and-extend;logMAR:logarithm of the minimumangle of resolution;SD:standard deviation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from\u003c/p\u003e\n\u003cp\u003ethe corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethics committee at Second Affiliated Hospital of Chongqing Medical University and conducted in accordance with the principles of the Helsinki Declaration. Written informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone of the authors have any competing interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Project of Chongqing Health and Family Planning Commission (ZY20162085).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHXY contributed to study design, statistical analyze, data acquisition and manuscript preparation; ZMM, LJT and WX contributed to literature research and clinical studies; ZMM contributed to manuscript review; ZZ was the guarantor of integrity of the entire study and contributed to study concepts, and data analyze; The final version of the manuscript has been read and approved by all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all participants in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKohli P, Patel BC. Macular Edema. StatPearls. Treasure Island (FL):StatPearls Publishing;2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, Rothschild PR, Omri S, G\u0026eacute;liz\u0026eacute; E, Jonet L, Delaunay K, De Kozak Y, Berdugo M, Zhao M, Crisanti P, Behar-Cohen F. Mechanisms of macular edema: Beyond the surface. Prog Retin Eye Res. 2018;63:20\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIijima H. Mechanisms of vision loss in eyes with macular edema associated with retinal vein occlusion. Jpn J Ophthalmol. 2018;62(3):265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG. BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. 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Outcomes of Eyes Lost to Follow-up with Proliferative Diabetic Retinopathy That Received Panretinal Photocoagulation versus Intravitreal Anti-Vascular Endothelial Growth Factor. Ophthalmology. 2019;126(3):407\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsunaga DR, Salabati M, Obeid A, Wibbelsman TD, Wu C, Mahmoudzadeh R, Ojalvo I, Bilello J, Sivalingam A, Ho AC, Chiang A, Hsu J. Outcomes of Eyes With Diabetic Macular Edema That Are Lost to Follow-up After Anti-Vascular Endothelial Growth Factor Therapy. Am J Ophthalmol. 2022;233:1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong P, Xu Y, Zha M, Zhang Y, Rudan I. Global epidemiology of retinal vein occlusion: a systematic review and meta-analyze of prevalence, incidence, and risk factors. J Glob Health. 2019;9(1):010427.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt-Erfurth U, Garcia-Arumi J, Gerendas BS, Midena E, Sivaprasad S, Tadayoni R, Wolf S, Loewenstein A. Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2019;242(3):123\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020;7(7):CD009510.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKelkar A, Webers C, Shetty R, Kelkar J, Labhsetwar N, Pandit A, Malode M, Tidke S. Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion, age-related macular degeneration, and diabetic macular edema. Indian J Ophthalmol. 2020;68(10):2143\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalabati M, Mahmoudzadeh R, Wong JC, Patel D, Patel SN, Obeid A, Sivalingam A, Vander JF, Garg SJ, Ho AC, Regillo CD, Hsu J. Outcomes of eyes with retinal vein occlusion that are lost to follow-up after antivascular endothelial growth factor therapy. Br J Ophthalmol. 2022;106(12):1742\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgura Y, Roider J, Korobelnik J-F, Holz FG, Simader C, Schmidt-Erfurth U, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, et al. Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study. Am J Ophthalmol. 2014;158:1032\u0026ndash;1038e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark DG, Jeong WJ, Park JM, Kim JY, Ji YS, Sagong M. Prospective trial of treat-and-extend regimen with aflibercept for branch retinal vein occlusion: 1-year results of the PLATON trial. Graefes Arch Clin Exp Ophthalmol. 2021;259(10):2879\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTerao R, Fujino R, Ahmed T. Risk Factors and Treatment Strategy for Retinal Vascular Occlusive Diseases. J Clin Med. 2022;11(21):6340.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012;119(4):802\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrogan K, Precup M, Rodger A, Young D, Gilmour DF. Pre-treatment clinical features in central retinal vein occlusion that predict visual outcome following intravitreal ranibizumab. BMC Ophthalmol. 2018;18(1):37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSen P, Gurudas S, Ramu J, Patrao N, Chandra S, Rasheed R, Nicholson L, Peto T, Sivaprasad S, Hykin P. Predictors of Visual Acuity Outcomes after Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion. Ophthalmol Retina. 2021;5(11):1115\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"retinal vein occlusion, anti-vascular endothelial growth factor, loss of follow-up, influential factors.","lastPublishedDoi":"10.21203/rs.3.rs-2608586/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2608586/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003ePatients with macular edema (ME) secondary to retinal vein occlusion (RVO) who received at least one intravitreal injection of anti-vascular endothelial growth factor therapy (VEGF) and lost to follow-up (LTFU) for more than six months were analyzed to investigate the factors contributing to the LTFU and the prognosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This was a retrospective, single-center study to analyze the causes and prognosis of LTFU over six months in RVO-ME patients treated with intravitreal anti-VEGF injections at our institution from January 2019 to August 2022 and to collect patients' baseline characteristics along with the number of injections before LTFU, primary disease, best corrected visual acuity (BCVA) before LTFU and after return visit, central macular thickness (CMT), months before LTFU and after LTFU, reasons for LTFU, and complications, to analyze the factors affecting visual outcome at a return visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e This study included 125 patients with LTFU; 103 remained LTFU after six months, and 22 returned after LTFU. The common reason for LTFU was \"no improvement in vision\" (34.4%), followed by \"transport inconvenience\" (22.4%), 16 patients (12.8%) were unwilling to visit the clinic, 15 patients (12.0%) had already elected to seek treatment elsewhere, 12 patients (9.6%) were not seen in time due to the 2019-nCov epidemic, and 11 patients (8.8%) cannot do it due to financial reasons. The number of injections before LTFU was a risk factor for LTFU (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). LogMAR at the initial visit (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.001), CMT at the initial visit (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05), CMT before the LTFU (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.001), and CMT after the return visit (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05) were influential factors for logMAR at the return visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eMost RVO-ME patients were LTFU after anti-VEGF therapy. Long-term LTFU is greatly detrimental to the visual quality of patients; thus, the management of RVO-ME patients in follow-up should be considered.\u003c/p\u003e","manuscriptTitle":"Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-02 19:54:43","doi":"10.21203/rs.3.rs-2608586/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-04-18T12:05:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-04-17T08:11:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-04-08T16:27:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6e7acb81-b985-4694-9e45-791914be24cb","date":"2023-03-31T14:09:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3f6c467a-de2b-4cf9-a292-2f749d569947","date":"2023-03-29T20:03:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-03-29T19:15:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-03-18T12:18:55+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-02-27T10:33:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-02-27T10:30:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2023-02-20T15:18:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd5b466d-fd27-47a4-a075-d0d9cd84901e","owner":[],"postedDate":"March 2nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:30:41+00:00","versionOfRecord":{"articleIdentity":"rs-2608586","link":"https://doi.org/10.1186/s12886-023-03018-9","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2023-06-12 21:11:51","publishedOnDateReadable":"June 12th, 2023"},"versionCreatedAt":"2023-03-02 19:54:43","video":"","vorDoi":"10.1186/s12886-023-03018-9","vorDoiUrl":"https://doi.org/10.1186/s12886-023-03018-9","workflowStages":[]},"version":"v1","identity":"rs-2608586","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2608586","identity":"rs-2608586","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}