Post-Vaccination SARS-CoV-2 IgG Antibody Titres in Retinal Vein Occlusion Patients: A Cross-Sectional Analysis

Post-Vaccination SARS-CoV-2 IgG Antibody Titres in Retinal Vein Occlusion Patients: A Cross-Sectional Analysis | 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 Post-Vaccination SARS-CoV-2 IgG Antibody Titres in Retinal Vein Occlusion Patients: A Cross-Sectional Analysis Mamta Verma, Jitender Phogat, Manisha Nada, Aparna Parmar, Rajender Singh Chauhan, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8415709/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: The objective of the present study is to examine the levels of SARS-CoV-2 IgG antibody titres post COVID-19 vaccine in retinal vein occlusion (RVO) patients and in healthy control group; study conducted at the Regional Institute of Ophthalmology, Pt. B.D. Sharma PGIMS, Rohtak (Haryana), India. Methods: This study enrolled 215 patients with a confirmed diagnosis of retinal vein occlusion (RVO) based on comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, fundus examination, optical coherence tomography and fluorescence angiography. At presentation, all patients presented with sudden painless diminution of vision in affected eye with no other signs of recent SARS-CoV-2 infection. Patients with preexisting Type 2 Diabetes Mellitus, hypertension and old vascular occlusion were excluded. A control group of 100 age-matched healthy individuals was also included. Clinical variables such as sex distribution, best-corrected visual acuity, fundus characteristics, temporal profile of RVO onset, and history of COVID-19 infection and hospitalisation as well as details of COVID-19 vaccination were documented. Quantitative estimation of SARS-CoV-2 antibody titres (IgG and IgM) in both cases and controls was performed using a standardized enzyme-linked immunosorbent assay (ELISA). Results: The mean SARS-CoV-2 IgG antibody titres in the RVO group who have received two COVID-19 vaccines (190.80 ± 20.06 pg/nm) was significantly higher than in the control group (111.45 ± 18.61 pg/nm), indicating a potential association between post COVID -19 vaccination elevated IgG antibody titres in RVO patients (p < 0.001). IgM levels were negative in both groups. All enrolled patients as well as controls were vaccinated with 2 doses of ChAdOx1 n CoV- 19 Corona Virus Vaccine, named as COVISHIELD ; It is a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein. There was no significant history of COVID-19 infection as well as hospitalisation in both groups. The mean duration between two vaccine dose was 4-6 weeks , all participants included in study have received last vaccine before 6-7 months of study. The low standard errors (2.40 for controls, 1.37 for RVO) suggest consistency within each group, and the bar chart illustrates the marked elevation in IgG titres levels among RVO patients. However, no significant association was observed between age and COVID-19 antibody titres in RVO patients, nor between antibody titres and sex. Conclusion: This study demonstrates a strong correlation of post COVID- 19 vaccines related elevation of SARS-CoV-2 IgG antibody titres and retinal vein occlusion in our cohort, representing the first report of such an association from India. COVID-19 IgG antibodies post-COVID complications COVID-19 Vaccine retinal vascular disease retinal vein occlusion SARS-CoV-2 Figures Figure 1 Figure 2 Figure 3 Summary After Vaccination Against COVID-19, SARS-CoV-2 IgG antibody titers were markedly elevated in RVO patients compared to controls (p < 0.001), while sex and age showed no significant influence. These findings suggest elevated titers are a characteristic feature of RVO, supporting a strong association with thromboembolic events after receiving the COVID-19 vaccine. Introduction Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly transmissible beta coronavirus, is the causative agent of COVID-19. Although most infected individuals experience mild to moderate disease, approximately 14–31% of symptomatic, unvaccinated patients progress to require hospitalization, and among those admitted, 2–27% necessitate intensive care support. ( 1 ) Pulmonary involvement is a hallmark of COVID-19 and frequently manifests as dry cough, nasal discharge, dyspnoea, and fever. Beyond respiratory symptoms, COVID-19 is strongly associated with thrombotic complications involving both arterial and venous systems. The infection promotes a prothrombotic milieu characterized by hypercoagulability, elevated D-dimer, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), and increased fibrin degradation products. Following respiratory or systemic infections, individuals carry a three- to six-fold increased risk of arterial thrombotic events such as myocardial infarction and ischemic stroke, and a two- to three-fold higher risk of venous events such as deep vein thrombosis and pulmonary embolism. ( 2 ) ( 3 ) Ophthalmic sequelae of SARS-CoV-2 have been increasingly recognized, with retinal vein occlusion (RVO) reported among vitreoretinal presentations. The pathogenesis of RVO in COVID-19 is thought to involve thromboembolic events, endothelial dysfunction, systemic hypoxia, and a procoagulant state. Virchow’s triad—hypercoagulability, endothelial injury, and circulatory stasis—remains central to its development.( 4 ) RVO is the second most common retinal vascular disorder after diabetic retinopathy. Based on the site of occlusion, it is classified into central retinal vein occlusion (CRVO), hemispheric retinal vein occlusion (HRVO), and branch retinal vein occlusion (BRVO).( 5 ) Clinically, RVO presents with sudden, painless visual impairment of variable severity. Funduscopic findings include venous dilation and tortuosity, intraretinal haemorrhages (blot and flame-shaped), cotton wool spots, optic disc oedema, and macular swelling. In CRVO, haemorrhages typically involve all quadrants; in HRVO, they are confined to the superior or inferior half of the retina; and in BRVO, they are restricted to the vascular territory of the affected branch vein. Vision loss primarily results from macular ischemia or oedema.( 6 ) Although the precise aetiology of RVO is not fully understood, thrombosis is widely implicated. In CRVO, thrombus formation generally occurs within the central retinal vein at or just posterior to the lamina cribrosa. Posterior occlusions with multiple venous tributaries may preserve collateral circulation and reduce ischemia. In BRVO, arteriovenous crossing sites predispose to venous obstruction due to turbulent flow and arterial compression, compounded by endothelial changes associated with systemic cardiovascular risk factors.( 4 ) Comparisons between RVO and systemic venous thromboembolic conditions such as deep vein thrombosis further support its thrombotic basis.( 7 ) Microvascular thrombosis has been well documented in COVID-19, and rare cases of vaccine-induced immune thrombotic thrombocytopenia have been observed following administration of ChAdOx1 nCoV-19. ( 8 ) Rare but serious thrombotic incidents in relation to thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), have been observed since the vaccine rollout. ( 9 ) Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. ( 10 ) While the number of thromboembolic events post-adenoviral vaccines has been well-documented in the medical literature, there has been limited information regarding thrombosis development after receiving a messenger RNA (mRNA)-based vaccine. ( 11 ) Retinal venous occlusions, which are readily identifiable on fundus examination, may therefore represent an ocular manifestation of this systemic thrombo inflammatory process. Though the diagnosis of SARS-CoV-2 infection is traditionally confirmed by reverse transcription polymerase chain reaction (RT-PCR) testing of nasopharyngeal, sputum, or bronchoalveolar lavage samples. More recently, the detection of virus-specific IgM and IgG antibodies has been accepted as supportive evidence of infection, although the kinetics of antibody response remain incompletely defined.( 8 ) IgM antibodies are usually detectable from day 4 after infection, reach peak levels around day 20, and subsequently decline. IgG antibodies emerge approximately one week after symptom onset, peak by the fourth week, and persist at high levels, providing long-term immunity and immunological memory. Severe disease is often associated with a more pronounced IgM and IgG response. ( 12 ) Materials and Methods Study subjects A total of 215 patients with retinal vein occlusion (RVO) were consecutively recruited from the Retina Clinic, Regional Institute of Ophthalmology, PGIMS, Rohtak, Haryana, India. Written informed consent was obtained from all participants or their legal guardians prior to enrolment. The study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Human Ethical Committee (IHEC), Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India. Based on the findings as reported by Ashkenazy et al the prevalence of central retinal vein occlusion following COVID-19 was 42%. Assuming an absolute precision of 10%, with an alpha error of 5% and 80% power of the study, we calculated the sample size according to following formula: N = [(Zalpha)^2 x p x (1-p]/ (d)^2 where, p = proportion in sample (0.42) d = margin of error (0.10) Zalpha = 3.84 (at 95% confidence interval). Inclusion criteria for the RVO cohort comprised patients of age 30 years to 60 years of both genders with a recent onset of sudden painless diminution of vision and history of minimum 2 doses of ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant), post vaccine duration was 6–7 months, without a history of diabetes, systemic hypertension, or other comorbidities known to predispose to RVO. Detailed history about COVID-19 infection, contact history and hospitalisation due to COVID-19 was taken. The diagnosis was established through comprehensive ophthalmic evaluation, including dialated ophthalmoscopy and optical coherence tomography and fluorescence angiography. Peripheral venous blood samples were collected from all patients and controls for SARS-CoV-2 IgG and IgM antibody testing using a commercially available enzyme-linked immunosorbent assay (ELISA). For comparison, 100 age-matched, unrelated healthy individuals were recruited from the community during outreach programs and health camps. All control participants underwent a complete ophthalmic assessment, which included measurement of best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, and documentation of COVID-19 vaccination status. Individuals with any ocular pathology other than refractive errors (e.g., cataract, macular haemorrhage, or age-related macular degeneration at any stage) were excluded from the control group. Ophthalmological evaluation All participants underwent anterior segment evaluation with slit-lamp biomicroscopy. A detailed retinal assessment was performed using indirect ophthalmoscopy. In addition, patients diagnosed with retinal vein occlusion were further evaluated with optical coherence tomography (OCT) and fluorescence angiography to document macular and retinal structural changes. COVID-19 AND Vaccination history Detailed history of COVID-19 infection, contact history, hospitalisation Vaccination history, type of vaccine received and duration post vaccine when sudden diminution was noted and presented to retina clinic, were recorded. COVID − 19 Antibody Titres calculation IgG and IgM titres in serum were measured in 100 healthy controls and 215 patients with RVO. The analysis was conducted using the Covid 19 (IgM + IgG + IgA) Microlisa (human) ELISA Kit (J.Mitra & Co. Pvt. Ltd, catalog no. IR200196) which is based on ‘double antigen sandwich ELISA’ with 96.72% sensitivity and 100% specificity, by following the manufacturer’s protocol. The absorbance was measured on the ELISA microplate reader. (Fig. 1 and Fig. 2 ) Statistical Analysis The statistical analysis was carried out with the assistance of SPSS 22.0. subsequently was decided to use the Levene’s test to compare the quantitative result between Covid 19 IgG antibody titres in retinal vein occlusion patients and the controls. Results were interpreted as per guidelines of manufacturer ( 11 interprets positive. Whole study population was found, negative for IgM antibodies. Results Assessment of Post COVID − 19 Vaccination IgG Antibody Titres in Control and in RVO Patients In the present study, a marked difference was observed in the mean COVID-19 IgG antibody titres between patients diagnosed with RVO and healthy controls after 6–7 months post 2 doses of ChAdOx1 n CoV- 19 Corona Virus Vaccine, named as COVISHIELD. The RVO group demonstrated a mean antibody titre of 190.80 ± 20.06 p g/nm, which was significantly higher than the mean titre of 111.45 ± 18.61 p g /nm ( p < 0.001) recorded in the control group. The standard error of the mean was 1.37 for the RVO group and 2.40 for the control group, suggesting lower variability and a relatively larger sample precision in the RVO cohort (Table 1 , Fig. 3 ). Table 1 The COVID-19 antibody titer in patients diagnosed as Control and RVO. Diagnosis N Mean Std. Deviation Std. Error Mean Control 100 111.45 18.61 2.4 RVO 215 190.8 20.06 1.37 To statistically evaluate this difference, an independent samples t-test was performed. Levene’s test for equality of variances indicated a significant result (F = 5.553, p = 0.019), demonstrating that the assumption of equal variances was not met; therefore, the analysis was conducted under the “equal variances not assumed” condition. The t-test confirmed that the mean antibody titre in the RVO group was significantly higher than that in the control group, with a mean difference of − 79.35 pg/nm (95% CI: −84.84 to − 73.87), yielding a highly significant t-value (t = − 28.699, p < 0.001). These results provide strong statistical evidence supporting an association of post COVID-19 vaccination related elevated COVID-19 I IgG antibody titres and the occurrence of RVO in the study population shown in Table 2 . Table 2 Independent Samples t-test for COVID-19 IgG Antibody Titres between Male and Female RVO Patients. Test F Sig. t df Sig. (2- tailed) Mean Difference Std. Error Difference 95% CI of Difference (Lower) 95% CI of Difference (Upper) Equal variances assumed 5.553 0.019 -27.507 273 0 -79.35 2.88 -85.03 -73.67 Equal variances not assumed — — -28.699 100.558 0 -79.35 2.76 -84.84 -73.87 Assessment of COVID-19 Antibody Titres in male and female RVO patients: In the RVO cohort, the mean COVID-19 IgG antibody titre was 190.68 ± 21.26 pg/nm in males and 191.02 ± 17.94 pg/nm in females, with standard errors of 1.82 and 2.02, respectively ( p < 0.001), indicating comparable variability between sexes (Table 3 ). Table 3 The difference between average COVID-19 IgG antibody titer in male and female patients diagnosed with RVO. Sex N Mean Std. Deviation Std. Error Mean Male 136 190.68 21.26 1.82 Female 79 191.02 17.94 2.02 Levene’s test for equality of variances showed no significant difference (F = 0.509, p = 0.477), allowing interpretation under the assumption of equal variances. An independent samples t-test revealed no statistically significant difference in mean titres between males and females (t = − 0.121, df = 213, p = 0.903), with a mean difference of − 0.35 pg/nm (95% CI: −5.95 to 5.26). These results indicate that sex does not have a measurable effect on COVID-19 IgG antibody titres in patients with RVO (Table 4 ). Table 4 Independent Samples t-test for COVID-19 IgG Antibody Titres between Male and Female RVO Patients Test F Sig. t df Sig. (2- tailed) Mean Difference Std. Error Difference 95% CI of Difference (Lower) 95% CI of Difference (Upper) Equal variances assumed 0.509 0.477 − 0.121 213 0.903 -0.35 2.84 -5.95 5.26 Equal variances not assumed — — − 0.127 185.776 0.899 -0.35 2.72 -5.71 5.02 Association between age and COVID-19 IgG antibody titres in RVO patients To explore the potential influence of age on COVID-19 antibody levels in patients with retinal vein occlusion, a Pearson’s correlation analysis was conducted. The analysis revealed a weak positive correlation between age and antibody titres (r = 0.124, p = 0.287, n = 76). Although the correlation coefficient indicated a slight tendency for antibody titres to increase with age, the association was not statistically significant. This suggests that within this cohort, age did not exert a measurable effect on the variation in COVID-19 antibody titres. These findings imply that the elevated antibody levels observed in RVO patients are unlikely to be attributable to age-related differences. Discussion In the present study, post vaccination SARS-CoV-2 IgG antibody titres were found to be significantly higher among patients with retinal vein occlusion (RVO) compared to healthy controls, suggesting a potential link between post vaccination retinal venous thrombosis.( 13 ) There were no signs and symptoms of recent infection of SARS-CoV-2 virus and IgM titres were negative in all study population.( 14 ) No significant differences in antibody levels were observed between male and female RVO patients, and no correlation with age was detected, indicating that the immune response in this cohort was not strongly influenced by demographic factors.( 15 ) COVID-19 is increasingly recognized as a systemic prothrombotic condition.( 1 ) The virus can compromise endothelial integrity through direct invasion and immune-mediated injury, thereby triggering coagulation cascades, promoting platelet activation, and contributing to microvascular obstruction.( 16 ) Elevated antibody titers may reflect either prior infection, contact history with COVID-19 and robust post-vaccination immune responses, both of which have been linked to systemic inflammation and hypercoagulability. ( 12 ) Multiple studies have demonstrated alterations in innate and adaptive immune responses in COVID-19, accompanied by a marked release of pro-inflammatory cytokines, commonly described as a “cytokine storm.”( 17 ) This dysregulated immune activation promotes “immunothrombosis,” a process that substantially increases the risk of thrombosis. ( 18 ) ( 19 )( 20 ) Vaccination against SARS-CoV-2, while highly effective, has also been associated with rare but serious thrombotic complications, such as venous thromboembolism (VTE) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Reports of these adverse events led to temporary pauses in vaccination campaigns in some countries.( 21 )( 22 ) Notably, VITT has been observed almost exclusively with adenoviral vector-based vaccines, such as ChAdOx1 nCoV-19 and Ad26.COV2.S.( 23 ) According to 2022 data from the Vaccine Adverse Event Reporting System (VAERS), the estimated incidence was approximately 3.8 per million doses (about 1 in 263,000). By contrast, thromboembolic events following mRNA-based vaccines (BNT162b2 and mRNA-1273) have been exceedingly rare. ( 24 ) ( 25 ) In the VAERS analysis by See et al., among 57 reported cases of thrombosis with thrombocytopenia syndrome (TTS) between December 2020 and September 2021, only three occurred after mRNA vaccine administration. ( 23 ) This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. ( 10 ) Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), is a rare and potentially fatal disorder that was first described in healthy recipients of the COVID-19 vaccine. Two adenoviral vector-based vaccines have been implicated in causing VITT: ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV 2 .S (Johnson & Johnson). The incidence is reported to be around 1 per 100,000 to 250,000 vaccine recipients, although the numbers seem to vary. The syndrome is characterized by severe thrombocytopenia and thrombosis occurring five to 30 days after vaccine administration. ( 11 ) Limitations of the study and Future prospective Although this study provides preliminary insights, its interpretation is limited by the relatively small sample size and the absence of validation in external cohorts. Future investigations should aim to include larger and more diverse populations to improve generalizability, incorporate functional assays to clarify underlying mechanisms, and evaluate broader associations. Abbreviations ELISA Enzyme linked imminosorbent essay RVO Retinal vein occlusion CoVID 19 Corona virus disease of 2019 BRVO Branch retinal vein occlusion CRVO Central retinal vein occlusion HRVO Hemi retinal vein occlusion VITT Vaccine induced immune thrombotic thrombocytopenia Declarations Funding: None Conflict of interest: None Clinical trial number: Not applicable Ethical approval and consent to participate: This study was approved by Institutional Human Ethical Committee (HEC/2021/290) of Pandit Bhagwat Dayal university of health sciences, Rohtak, Haryana, India. All participants were provided written informed consent prior to their participation in the study. All procedures adhered to the principles outlined in the Declaration of Helsinki and conformed to the International Council for Harmonisation guidelines on Good Clinical Practice. Availability of data and material: The data that support the findings of this study are available from the corresponding author upon reasonable request. Consent for publication: Not Applicable. Author’s contribution: Mamta Verma conducted the research. Aparna Parmar collected the samples from patients and controls and performed the data analysis and interpretation. Anshu Yadav and Mukesh Tanwar drafted the main manuscript text. Jitender Phogat critically revised the manuscript for important intellectual content All authors contributed to finalizing the manuscript. Acknowledgement: The authors express gratitude to the patients and control participants, whose participation was indispensable for the completion of this study. References Parotto M, Gyöngyösi M, Howe K, Myatra SN, Ranzani O, Shankar-Hari M, et al. 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J Vasc Surg Venous Lymphat Disord. 2022;10(1):14–7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8415709","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":583533875,"identity":"cb24ce0a-4757-4d47-a348-6321cbbb99ac","order_by":0,"name":"Mamta Verma","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mamta","middleName":"","lastName":"Verma","suffix":""},{"id":583533876,"identity":"4f778675-1323-48b8-a0cf-84753b9e6b63","order_by":1,"name":"Jitender 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Thakur","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Rahul","middleName":"","lastName":"Thakur","suffix":""},{"id":583533881,"identity":"9d450213-5fa4-48d6-8cd1-d48934ac06dd","order_by":6,"name":"Mukesh Tanwar","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mukesh","middleName":"","lastName":"Tanwar","suffix":""},{"id":583533882,"identity":"59f16500-15c9-422d-8bf4-e74c1c6bf050","order_by":7,"name":"Anshu Yadav","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Anshu","middleName":"","lastName":"Yadav","suffix":""},{"id":583533883,"identity":"0aeafbb9-fd69-4fab-8344-4354c63a76cb","order_by":8,"name":"Chander prabha","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Chander","middleName":"","lastName":"prabha","suffix":""},{"id":583533885,"identity":"f9b64901-2c58-4635-94bc-bbfccb6b4e18","order_by":9,"name":"Sonam Gill","email":"","orcid":"","institution":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sonam","middleName":"","lastName":"Gill","suffix":""}],"badges":[],"createdAt":"2025-12-21 07:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8415709/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8415709/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101657379,"identity":"26d0efb1-bd26-4e08-af0c-db88e43845b8","added_by":"auto","created_at":"2026-02-02 10:16:54","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":482348,"visible":true,"origin":"","legend":"\u003cp\u003eCovid 19 Antibody Titer Kit.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8415709/v1/d891cb623a474a48bf208a55.jpeg"},{"id":101657377,"identity":"7cd1d59d-28c2-48ed-8cde-33fd45894a09","added_by":"auto","created_at":"2026-02-02 10:16:54","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":102368,"visible":true,"origin":"","legend":"\u003cp\u003eTiter well kit.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8415709/v1/f8db55890f67f154509050ef.jpeg"},{"id":101657378,"identity":"a3a97e56-837d-4a6e-a184-910bb1dca850","added_by":"auto","created_at":"2026-02-02 10:16:54","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31344,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Mean and Standard Deviation of COVID-19 Antibody Titers between Control and RVO Groups.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8415709/v1/0d682f6979c6011fc5e952cf.jpeg"},{"id":102737359,"identity":"af87d3a1-9797-4673-ab3f-49f4d634d6e9","added_by":"auto","created_at":"2026-02-16 06:41:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1428994,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8415709/v1/e547d572-edba-4caa-9ea0-98621b0a0535.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePost-Vaccination SARS-CoV-2 IgG Antibody Titres in Retinal Vein Occlusion Patients: A Cross-Sectional Analysis\u003c/p\u003e","fulltext":[{"header":"Summary","content":"\u003cp\u003eAfter Vaccination Against COVID-19, SARS-CoV-2 IgG antibody titers were markedly elevated in RVO patients compared to controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while sex and age showed no significant influence. These findings suggest elevated titers are a characteristic feature of RVO, supporting a strong association with thromboembolic events after receiving the COVID-19 vaccine.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly transmissible beta coronavirus, is the causative agent of COVID-19. Although most infected individuals experience mild to moderate disease, approximately 14\u0026ndash;31% of symptomatic, unvaccinated patients progress to require hospitalization, and among those admitted, 2\u0026ndash;27% necessitate intensive care support. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePulmonary involvement is a hallmark of COVID-19 and frequently manifests as dry cough, nasal discharge, dyspnoea, and fever. Beyond respiratory symptoms, COVID-19 is strongly associated with thrombotic complications involving both arterial and venous systems. The infection promotes a prothrombotic milieu characterized by hypercoagulability, elevated D-dimer, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), and increased fibrin degradation products. Following respiratory or systemic infections, individuals carry a three- to six-fold increased risk of arterial thrombotic events such as myocardial infarction and ischemic stroke, and a two- to three-fold higher risk of venous events such as deep vein thrombosis and pulmonary embolism. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOphthalmic sequelae of SARS-CoV-2 have been increasingly recognized, with retinal vein occlusion (RVO) reported among vitreoretinal presentations. The pathogenesis of RVO in COVID-19 is thought to involve thromboembolic events, endothelial dysfunction, systemic hypoxia, and a procoagulant state. Virchow\u0026rsquo;s triad\u0026mdash;hypercoagulability, endothelial injury, and circulatory stasis\u0026mdash;remains central to its development.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eRVO is the second most common retinal vascular disorder after diabetic retinopathy. Based on the site of occlusion, it is classified into central retinal vein occlusion (CRVO), hemispheric retinal vein occlusion (HRVO), and branch retinal vein occlusion (BRVO).(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Clinically, RVO presents with sudden, painless visual impairment of variable severity. Funduscopic findings include venous dilation and tortuosity, intraretinal haemorrhages (blot and flame-shaped), cotton wool spots, optic disc oedema, and macular swelling. In CRVO, haemorrhages typically involve all quadrants; in HRVO, they are confined to the superior or inferior half of the retina; and in BRVO, they are restricted to the vascular territory of the affected branch vein. Vision loss primarily results from macular ischemia or oedema.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough the precise aetiology of RVO is not fully understood, thrombosis is widely implicated. In CRVO, thrombus formation generally occurs within the central retinal vein at or just posterior to the lamina cribrosa. Posterior occlusions with multiple venous tributaries may preserve collateral circulation and reduce ischemia. In BRVO, arteriovenous crossing sites predispose to venous obstruction due to turbulent flow and arterial compression, compounded by endothelial changes associated with systemic cardiovascular risk factors.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Comparisons between RVO and systemic venous thromboembolic conditions such as deep vein thrombosis further support its thrombotic basis.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMicrovascular thrombosis has been well documented in COVID-19, and rare cases of vaccine-induced immune thrombotic thrombocytopenia have been observed following administration of ChAdOx1 nCoV-19. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eRare but serious thrombotic incidents in relation to thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), have been observed since the vaccine rollout. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eWhile the number of thromboembolic events post-adenoviral vaccines has been well-documented in the medical literature, there has been limited information regarding thrombosis development after receiving a messenger RNA (mRNA)-based vaccine. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Retinal venous occlusions, which are readily identifiable on fundus examination, may therefore represent an ocular manifestation of this systemic thrombo inflammatory process.\u003c/p\u003e \u003cp\u003eThough the diagnosis of SARS-CoV-2 infection is traditionally confirmed by reverse transcription polymerase chain reaction (RT-PCR) testing of nasopharyngeal, sputum, or bronchoalveolar lavage samples. More recently, the detection of virus-specific IgM and IgG antibodies has been accepted as supportive evidence of infection, although the kinetics of antibody response remain incompletely defined.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) IgM antibodies are usually detectable from day 4 after infection, reach peak levels around day 20, and subsequently decline. IgG antibodies emerge approximately one week after symptom onset, peak by the fourth week, and persist at high levels, providing long-term immunity and immunological memory. Severe disease is often associated with a more pronounced IgM and IgG response. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cstrong\u003eStudy subjects\u003c/strong\u003e \u003cp\u003eA total of 215 patients with retinal vein occlusion (RVO) were consecutively recruited from the Retina Clinic, Regional Institute of Ophthalmology, PGIMS, Rohtak, Haryana, India. Written informed consent was obtained from all participants or their legal guardians prior to enrolment. The study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Human Ethical Committee (IHEC), Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eBased on the findings as reported by Ashkenazy et al the prevalence of central retinal vein occlusion following COVID-19 was 42%. Assuming an absolute precision of 10%, with an alpha error of 5% and 80% power of the study, we calculated the sample size according to following formula:\u003c/p\u003e \u003cp\u003eN = [(Zalpha)^2 x p x (1-p]/ (d)^2\u003c/p\u003e \u003cp\u003ewhere, p\u0026thinsp;=\u0026thinsp;proportion in sample (0.42) d\u0026thinsp;=\u0026thinsp;margin of error (0.10) Zalpha\u0026thinsp;=\u0026thinsp;3.84 (at 95% confidence interval).\u003c/p\u003e \u003cp\u003eInclusion criteria for the RVO cohort comprised patients of age 30 years to 60 years of both genders with a recent onset of sudden painless diminution of vision and history of minimum 2 doses of ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant), post vaccine duration was 6\u0026ndash;7 months, without a history of diabetes, systemic hypertension, or other comorbidities known to predispose to RVO. Detailed history about COVID-19 infection, contact history and hospitalisation due to COVID-19 was taken. The diagnosis was established through comprehensive ophthalmic evaluation, including dialated ophthalmoscopy and optical coherence tomography and fluorescence angiography. Peripheral venous blood samples were collected from all patients and controls for SARS-CoV-2 IgG and IgM antibody testing using a commercially available enzyme-linked immunosorbent assay (ELISA).\u003c/p\u003e \u003cp\u003eFor comparison, 100 age-matched, unrelated healthy individuals were recruited from the community during outreach programs and health camps. All control participants underwent a complete ophthalmic assessment, which included measurement of best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, and documentation of COVID-19 vaccination status. Individuals with any ocular pathology other than refractive errors (e.g., cataract, macular haemorrhage, or age-related macular degeneration at any stage) were excluded from the control group.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eOphthalmological evaluation\u003c/strong\u003e \u003cp\u003eAll participants underwent anterior segment evaluation with slit-lamp biomicroscopy. A detailed retinal assessment was performed using indirect ophthalmoscopy. In addition, patients diagnosed with retinal vein occlusion were further evaluated with optical coherence tomography (OCT) and fluorescence angiography to document macular and retinal structural changes.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCOVID-19 AND Vaccination history\u003c/strong\u003e \u003cp\u003eDetailed history of COVID-19 infection, contact history, hospitalisation Vaccination history, type of vaccine received and duration post vaccine when sudden diminution was noted and presented to retina clinic, were recorded.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCOVID \u0026minus;\u0026thinsp;19 Antibody Titres calculation\u003c/strong\u003e \u003cp\u003eIgG and IgM titres in serum were measured in 100 healthy controls and 215 patients with RVO. The analysis was conducted using the Covid 19 (IgM\u0026thinsp;+\u0026thinsp;IgG\u0026thinsp;+\u0026thinsp;IgA) Microlisa (human) ELISA Kit (J.Mitra \u0026amp; Co. Pvt. Ltd, catalog no. IR200196) which is based on \u0026lsquo;double antigen sandwich ELISA\u0026rsquo; with 96.72% sensitivity and 100% specificity, by following the manufacturer\u0026rsquo;s protocol. The absorbance was measured on the ELISA microplate reader. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eStatistical Analysis\u003c/strong\u003e \u003cp\u003eThe statistical analysis was carried out with the assistance of SPSS 22.0. subsequently was decided to use the \u003cem\u003eLevene\u0026rsquo;s\u003c/em\u003e test to compare the quantitative result between Covid 19 IgG antibody titres in retinal vein occlusion patients and the controls. Results were interpreted as per guidelines of manufacturer (\u0026lt;\u0026thinsp;9 interprets as negative, 9\u0026ndash;11 interprets equivocal, \u0026gt;\u0026thinsp;11 interprets positive. Whole study population was found, negative for IgM antibodies.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cstrong\u003eAssessment of Post COVID \u0026minus;\u0026thinsp;19 Vaccination IgG Antibody Titres in Control and in RVO Patients\u003c/strong\u003e \u003cp\u003eIn the present study, a marked difference was observed in the mean COVID-19 IgG antibody titres between patients diagnosed with RVO and healthy controls after 6\u0026ndash;7 months post 2 doses of ChAdOx1 n CoV- 19 Corona Virus Vaccine, named as COVISHIELD. The RVO group demonstrated a mean antibody titre of 190.80\u0026thinsp;\u0026plusmn;\u0026thinsp;20.06 p g/nm, which was significantly higher than the mean titre of 111.45\u0026thinsp;\u0026plusmn;\u0026thinsp;18.61 p g /nm (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) recorded in the control group. The standard error of the mean was 1.37 for the RVO group and 2.40 for the control group, suggesting lower variability and a relatively larger sample precision in the RVO cohort (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe COVID-19 antibody titer in patients diagnosed as Control and RVO.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStd. Deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStd. Error Mean\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e111.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e190.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo statistically evaluate this difference, an independent samples t-test was performed. Levene\u0026rsquo;s test for equality of variances indicated a significant result (F\u0026thinsp;=\u0026thinsp;5.553, p\u0026thinsp;=\u0026thinsp;0.019), demonstrating that the assumption of equal variances was not met; therefore, the analysis was conducted under the \u0026ldquo;equal variances not assumed\u0026rdquo; condition. The t-test confirmed that the mean antibody titre in the RVO group was significantly higher than that in the control group, with a mean difference of \u0026minus;\u0026thinsp;79.35 pg/nm (95% CI: \u0026minus;84.84 to \u0026minus;\u0026thinsp;73.87), yielding a highly significant t-value (t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;28.699, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results provide strong statistical evidence supporting an association of post COVID-19 vaccination related elevated COVID-19 I IgG antibody titres and the occurrence of RVO in the study population shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndependent Samples t-test for COVID-19 IgG Antibody Titres between Male and Female RVO Patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSig.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSig. (2-\u003c/p\u003e \u003cp\u003etailed)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003cp\u003eDifference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eStd. Error Difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95% CI of\u003c/p\u003e \u003cp\u003eDifference (Lower)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e95% CI of\u003c/p\u003e \u003cp\u003eDifference (Upper)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual\u003c/p\u003e \u003cp\u003evariances assumed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-27.507\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-79.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-85.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-73.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual variances not assumed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-28.699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-79.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-84.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-73.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eAssessment of COVID-19 Antibody Titres in male and female RVO patients:\u003c/h3\u003e\n\u003cp\u003eIn the RVO cohort, the mean COVID-19 IgG antibody titre was 190.68\u0026thinsp;\u0026plusmn;\u0026thinsp;21.26 pg/nm in males and 191.02\u0026thinsp;\u0026plusmn;\u0026thinsp;17.94 pg/nm in females, with standard errors of 1.82 and 2.02, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating comparable variability between sexes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe difference between average COVID-19 IgG antibody titer in male and female patients diagnosed with RVO.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStd. Deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStd. Error Mean\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e190.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e191.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLevene\u0026rsquo;s test for equality of variances showed no significant difference (F\u0026thinsp;=\u0026thinsp;0.509, p\u0026thinsp;=\u0026thinsp;0.477), allowing interpretation under the assumption of equal variances. An independent samples t-test revealed no statistically significant difference in mean titres between males and females (t\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.121, df\u0026thinsp;=\u0026thinsp;213, p\u0026thinsp;=\u0026thinsp;0.903), with a mean difference of \u0026minus;\u0026thinsp;0.35 pg/nm (95% CI: \u0026minus;5.95 to 5.26). These results indicate that sex does not have a measurable effect on COVID-19 IgG antibody titres in patients with RVO (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndependent Samples t-test for COVID-19 IgG Antibody Titres between Male and Female RVO Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSig.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSig. (2-\u003c/p\u003e \u003cp\u003etailed)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean Difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eStd. Error Difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95% CI of\u003c/p\u003e \u003cp\u003eDifference (Lower)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e95% CI of\u003c/p\u003e \u003cp\u003eDifference (Upper)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual variances assumed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.509\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-5.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual variances not assumed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;0.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e185.776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.899\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-5.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAssociation between age and COVID-19 IgG antibody titres in RVO patients\u003c/strong\u003e \u003cp\u003eTo explore the potential influence of age on COVID-19 antibody levels in patients with retinal vein occlusion, a Pearson\u0026rsquo;s correlation analysis was conducted. The analysis revealed a weak positive correlation between age and antibody titres (r\u0026thinsp;=\u0026thinsp;0.124, p\u0026thinsp;=\u0026thinsp;0.287, n\u0026thinsp;=\u0026thinsp;76). Although the correlation coefficient indicated a slight tendency for antibody titres to increase with age, the association was not statistically significant. This suggests that within this cohort, age did not exert a measurable effect on the variation in COVID-19 antibody titres. These findings imply that the elevated antibody levels observed in RVO patients are unlikely to be attributable to age-related differences.\u003c/p\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, post vaccination SARS-CoV-2 IgG antibody titres were found to be significantly higher among patients with retinal vein occlusion (RVO) compared to healthy controls, suggesting a potential link between post vaccination retinal venous thrombosis.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) There were no signs and symptoms of recent infection of SARS-CoV-2 virus and IgM titres were negative in all study population.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) No significant differences in antibody levels were observed between male and female RVO patients, and no correlation with age was detected, indicating that the immune response in this cohort was not strongly influenced by demographic factors.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCOVID-19 is increasingly recognized as a systemic prothrombotic condition.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The virus can compromise endothelial integrity through direct invasion and immune-mediated injury, thereby triggering coagulation cascades, promoting platelet activation, and contributing to microvascular obstruction.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Elevated antibody titers may reflect either prior infection, contact history with COVID-19 and robust post-vaccination immune responses, both of which have been linked to systemic inflammation and hypercoagulability. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMultiple studies have demonstrated alterations in innate and adaptive immune responses in COVID-19, accompanied by a marked release of pro-inflammatory cytokines, commonly described as a \u0026ldquo;cytokine storm.\u0026rdquo;(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) This dysregulated immune activation promotes \u0026ldquo;immunothrombosis,\u0026rdquo; a process that substantially increases the risk of thrombosis. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eVaccination against SARS-CoV-2, while highly effective, has also been associated with rare but serious thrombotic complications, such as venous thromboembolism (VTE) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Reports of these adverse events led to temporary pauses in vaccination campaigns in some countries.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) Notably, VITT has been observed almost exclusively with adenoviral vector-based vaccines, such as ChAdOx1 nCoV-19 and Ad26.COV2.S.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) According to 2022 data from the Vaccine Adverse Event Reporting System (VAERS), the estimated incidence was approximately 3.8 per million doses (about 1 in 263,000).\u003c/p\u003e \u003cp\u003eBy contrast, thromboembolic events following mRNA-based vaccines (BNT162b2 and mRNA-1273) have been exceedingly rare. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) In the VAERS analysis by See et al., among 57 reported cases of thrombosis with thrombocytopenia syndrome (TTS) between December 2020 and September 2021, only three occurred after mRNA vaccine administration. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eVaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), is a rare and potentially fatal disorder that was first described in healthy recipients of the COVID-19 vaccine. Two adenoviral vector-based vaccines have been implicated in causing VITT: ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV\u003csub\u003e2\u003c/sub\u003e.S (Johnson \u0026amp; Johnson). The incidence is reported to be around 1 per 100,000 to 250,000 vaccine recipients, although the numbers seem to vary. The syndrome is characterized by severe thrombocytopenia and thrombosis occurring five to 30 days after vaccine administration. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations of the study and Future prospective\u003c/strong\u003e \u003cp\u003eAlthough this study provides preliminary insights, its interpretation is limited by the relatively small sample size and the absence of validation in external cohorts. Future investigations should aim to include larger and more diverse populations to improve generalizability, incorporate functional assays to clarify underlying mechanisms, and evaluate broader associations.\u003c/p\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eELISA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEnzyme linked imminosorbent essay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRVO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRetinal vein occlusion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCoVID 19\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCorona virus disease of 2019\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eBRVO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBranch retinal vein occlusion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCRVO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral retinal vein occlusion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eHRVO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemi retinal vein occlusion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eVITT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVaccine induced immune thrombotic thrombocytopenia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was approved by Institutional Human Ethical Committee (HEC/2021/290) of Pandit Bhagwat Dayal university of health sciences, Rohtak, Haryana, India. All participants were provided written informed consent prior to their participation in the study. All procedures adhered to the principles outlined in the Declaration of Helsinki and conformed to the International Council for Harmonisation guidelines on Good Clinical Practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contribution:\u0026nbsp;\u003c/strong\u003eMamta Verma conducted the research. Aparna Parmar collected the samples from patients and controls and performed the data analysis and interpretation. Anshu \u0026nbsp; Yadav and Mukesh Tanwar drafted the main manuscript text. Jitender Phogat critically revised the manuscript for important intellectual content All authors contributed to finalizing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eThe authors express gratitude to the patients and control participants, whose participation was indispensable for the completion of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eParotto M, Gy\u0026ouml;ngy\u0026ouml;si M, Howe K, Myatra SN, Ranzani O, Shankar-Hari M, et al. Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations. The Lancet Respiratory Medicine. Volume 11. Elsevier Ltd; 2023. pp. 739\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of Myocardial Infarction and Stroke after Acute Infection or Vaccination [Internet]. Vol. 25, n engl j med. 2004. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003c/span\u003e\u003cspan address=\"http://www.nejm.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClayton TC, Gaskin M, Meade TW. Recent respiratory infection and risk of venous thromboembolism: Case-control study through a general practice database. Int J Epidemiol. 2011;40(3):819\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUllah I, Sohail A, Shah MUFA, Khurshid M, Diwan MN, Qadir A, et al. Central Retinal Vein Occlusion in patients with COVID-19 infection: A systematic review. Annals of Medicine and Surgery. Volume 71. Elsevier Ltd; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCugati S, Jie;, Wang J, Rochtchina E, Mitchell P. Ten-Year Incidence of Retinal Vein Occlusion in an Older Population The Blue Mountains Eye Study.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaria N. Clinical Ophthalmology Dovepress Retinal vein occlusion: pathophysiology and treatment options [Internet]. Clinical Ophthalmology. 2010. Available from: www.dovepress.com.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshkenazy N, Patel NA, Sridhar J, Yannuzzi NA, Belin PJ, Kaplan R, et al. Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors. Ophthalmol Retina. 2022;6(6):520\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamayoshi S, Yasuhara A, Ito M, Akasaka O, Nakamura M, Nakachi I et al. Antibody titers against SARS-CoV-2 decline, but do not disappear for several months. EClinicalMedicine. 2021;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuhaimi SNAA, Zaki IAH, Noordin ZM, Hussin NSM, Ming LC, Zulkifly HH. COVID-19 vaccine-induced immune thrombotic thrombocytopenia: a review. Clinical and Experimental Vaccine Research. Volume 12. Korean Vaccine Society; 2023. pp. 265\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnastasiou T, Sanidas E, Lytra T, Mimikos G, Gogas H, Mantzourani M. Update on Thromboembolic Events After Vaccination Against COVID-19. Vol. 13, Vaccines. Multidisciplinary Digital Publishing Institute (MDPI); 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBekal S, Husari G, Okura M, Huang CA, Bukari MS. Thrombosis Development After mRNA COVID-19 Vaccine Administration: A Case Series. Cureus. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi JX, Wang YH, Bair H, Hsu SB, Chen C, Wei JCC et al. Risk assessment of retinal vascular occlusion after COVID-19 vaccination. NPJ Vaccines. 2023;8(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoman M, Indurkar A, George T, Sheth JU, Nair U. Rapid Onset Neovascular Glaucoma due to COVID-19-related Retinopathy. J Curr Glaucoma Pract. 2022;16(2):136\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka H, Nagasato D, Nakakura S, Tanabe H, Nagasawa T, Wakuda H, et al. Exacerbation of branch retinal vein occlusion post SARS-CoV2 vaccination Case reports. Med (United States). 2021;100(50):E28236.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParmar DP, Rathod JS, Karkhanawala MM, Bhole PK, Rathod DS. Foldscope: A smartphone based diagnostic tool for fungal keratitis. Indian J Ophthalmol. 2021;69(10):2836\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuadros S\u0026aacute;nchez C, Eg\u0026uuml;en CS, Gutierrez-Ezquerro R, Giralt-Peret L, Fonollosa A. Central Retinal Vein Occlusion Presumably Associated with Lupus Anticoagulant Induced by SARSCoV-2. Ocul Immunol Inflamm. 2022;30(7\u0026ndash;8):2010\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYahalomi T, Pikkel J, Arnon R, Pessach Y. Central retinal vein occlusion in a young healthy COVID-19 patient: A case report. Am J Ophthalmol Case Rep. 2020;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCatanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduction and Targeted Therapy. Volume 5. Springer Nature; 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thrombosis Research. Volume 194. Elsevier Ltd; 2020. pp. 101\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. Volume 395. Lancet Publishing Group; 2020. pp. 1033\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLatkin CA, Dayton L, Yi G, Konstantopoulos A, Boodram B. Trust in a COVID-19 vaccine in the U.S.: A social-ecological perspective. Soc Sci Med. 2021;270.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMahase E. AstraZeneca vaccine: Blood clots are extremely rare and benefits outweigh risks, regulators conclude. BMJ. 2021;373:n931.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSee I, Lale A, Marquez P, Streiff MB, Wheeler AP, Tepper NK, et al. Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination\u0026mdash;United States, December 2020 to August 2021. Ann Intern Med. 2022;175(4):513\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Maqbali JS, Rasbi S, Al, Kashoub MS, Hinaai AM, Al, Farhan H, Rawahi B, Al et al. A 59-year-old woman with extensive deep vein thrombosis and pulmonary thromboembolism 7 days following a first dose of the pfizer-biontech bnt162b2 mrna covid-19 vaccine. Am J Case Rep. 2021;22(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndraska EA, Kulkarni R, Chaudhary M, Sachdev U. Three cases of acute venous thromboembolism in females after vaccination for coronavirus disease 2019. J Vasc Surg Venous Lymphat Disord. 2022;10(1):14\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, IgG antibodies, post-COVID complications, COVID-19 Vaccine, retinal vascular disease, retinal vein occlusion, SARS-CoV-2","lastPublishedDoi":"10.21203/rs.3.rs-8415709/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8415709/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThe objective of the present study is to examine the levels of SARS-CoV-2 IgG antibody titres post COVID-19 vaccine in retinal vein occlusion (RVO) patients \u0026nbsp;\u0026nbsp;and in healthy control group; study conducted at the Regional Institute of Ophthalmology, Pt. B.D. Sharma PGIMS, Rohtak (Haryana), India.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study enrolled 215 patients with a confirmed diagnosis of retinal vein occlusion (RVO) based on comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, fundus examination, optical coherence tomography and fluorescence angiography. At presentation, all patients presented with sudden painless diminution of vision in affected eye with no other signs of recent SARS-CoV-2 infection. Patients with preexisting Type 2 Diabetes Mellitus, hypertension and old vascular occlusion were excluded. A control group of 100 age-matched healthy individuals was also included. Clinical variables such as sex distribution, best-corrected visual acuity, fundus characteristics, temporal profile of RVO onset, and history of COVID-19 infection and hospitalisation as well as details of COVID-19 vaccination were documented. Quantitative estimation of SARS-CoV-2 antibody titres (IgG and IgM) in both cases and controls was performed using a standardized enzyme-linked immunosorbent assay (ELISA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe mean SARS-CoV-2 IgG antibody titres in the RVO group who have received two COVID-19 vaccines (190.80 ± 20.06 pg/nm) was significantly higher than in the control group \u0026nbsp;(111.45 ± 18.61 pg/nm), indicating a potential association between post COVID -19 vaccination elevated IgG antibody titres in RVO patients (p \u0026lt; 0.001). IgM levels were negative in both groups. All enrolled patients as well as controls were vaccinated with 2 doses of ChAdOx1 n CoV- 19 Corona Virus Vaccine, named as COVISHIELD ; It is a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein. There was no significant history of COVID-19 infection as well as hospitalisation in both groups. The mean duration between two vaccine dose was 4-6 weeks , all participants included in study have received last vaccine before 6-7 months of study. The low standard errors (2.40 for controls, 1.37 for RVO) suggest consistency within each group, and the bar chart illustrates the marked elevation in IgG titres levels among RVO patients.\u003c/p\u003e\n\u003cp\u003eHowever, no significant association was observed between age and COVID-19 antibody titres in RVO patients, nor between antibody titres and sex.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study demonstrates a strong correlation of post COVID- 19 vaccines related elevation of SARS-CoV-2 IgG antibody titres and retinal vein occlusion in our cohort, representing the first report of such \u0026nbsp;an association from India.\u003c/p\u003e","manuscriptTitle":"Post-Vaccination SARS-CoV-2 IgG Antibody Titres in Retinal Vein Occlusion Patients: A Cross-Sectional Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 10:16:44","doi":"10.21203/rs.3.rs-8415709/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32a58933-747a-4c58-be19-136cd2e7fcbf","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T06:41:10+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-02 10:16:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8415709","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8415709","identity":"rs-8415709","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}