Retinal Vein Occlusion Research Articles

Visual outcomes and prognostic factors in ischaemic retinal vasculitis

PurposeOur aim was to describe the visual outcomes and determine the clinical factors in ischaemic retinal vasculitis (IRV) that were predictive of a poor visual prognosis or infectious aetiology.MethodsRetrospective cohort...

Infographic: Ranibizumab for macular oedema following branch retinal vein occlusion (BRAVO).

Infographic: Ranibizumab for macular oedema following branch retinal vein occlusion (BRAVO).

Characterization and prevalence of ocular comorbidities and risk of legal blindness across the United States

Background/ObjectivesVision loss is a top disability in the United States (US). Patients commonly present with multiple ocular diseases, but the extent to which this places them at risk for vision loss, and if sex and race impacts this, is poorly understood. This exploratory analysis evaluated which ocular comorbidities and demographics are at highest risk for visual impairment.Subjects/MethodsA retrospective cross-sectional study was conducted through the TriNetX Analytics Network, an aggregated network encompassing over 90 million insured and uninsured patients across 50 healthcare organizations from all regions in the US. Patients with diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), glaucoma, and uveitis were included in this study. Ocular diseases and visual impairment were determined through ICD-10 codes. Prevalence and odds ratios were calculated while stratifying by sex and racial demographics. Statistical analyses were completed using RStudio and Excel with 95% confidence intervals calculated.ResultsThe comorbid conditions with the highest prevalence of visual impairment were uveitis and RVO (39.94%), uveitis and neovascular AMD (37.61%), and uveitis and glaucoma (33.23%). The comorbidity with the highest odds for visual impairment was uveitis and RVO (POR 4.86; 95% CI 4.49, 5.26). Compared to white males, Black and Hispanic males were disproportionately affected by visual impairment across ocular comorbidities.ConclusionThis study quantified the prevalence and odds of visual impairment for unilateral and comorbid ocular disease, with the addition of uveitis causing the greatest increase. Black and Hispanic males were disproportionately affected by visual impairment across comorbid conditions.

Relationship between retinal volume changes and the prognosis of BRVO-ME treated with ranibizumab

BackgroundThis study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. MethodsThe 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. FindingsVisual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. InterpretationTreatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

Clinical Observation on the Treatment of Macular Edema Secondary to Retinal Vein Occlusion by Liuzi Yangmu Wan Combined with Conbercept Ophthalmic Injection

Clinical Observation on the Treatment of Macular Edema Secondary to Retinal Vein Occlusion by Liuzi Yangmu Wan Combined with Conbercept Ophthalmic Injection

Emerging role of vitamin D deficiency as a risk factor for retinal venous occlusions and need for public health measures for its prevention.

To estimate levels of serum vitamin D in patients of retinal vein occlusion (RVO) and compare with age- and sex-matched controls. A prospective case-control study of 54 patients of RVO and 54 age- and sex-matched attendants of patients presenting to a tertiary care hospital in Delhi was performed. Patients on vitamin D supplementations and RVO due to infective or immunological causes or patients of glaucoma were excluded. Serum vitamin D levels of all the study participants along with relevant blood investigations with history and examination were documented. Vitamin D deficiency was defined as <20 ng/ml. The mean serum vitamin D levels seen in RVO patients and the control group were 14.19 ± 5.23 ng/ml and 19.42 ± 10.27 ng/ml, respectively (P value = 0.001) with an odds ratio of 10.558 (CI = 2.34-47.50), indicating vitamin D deficiency to be strongly correlated with RVO. Maximum patients of RVO (46.3%) were seen during the winter season. The study noted hypertension [odds ratio 20.22 (CI = 5.812-70.347)], dyslipidemia, and anemia [odds ratio 4.107 (CI = 0.62-26.90)] to be the risk factors for RVO as previously proved in the literature. Smoking, diabetes, alcohol intake, and body mass index did not emerge as risk factors for RVO. Vitamin D deficiency is associated with RVO; hence, estimation of serum vitamin D levels should be advised as a part of routine investigations while looking for the cause of RVOs. Public health measures like food fortification with vitamin D micronutrients and public awareness towards increased sunlight exposure in the community are simple, inexpensive measures that can decrease the burden of sight-threatening disease of RVO in the community.

New Therapeutic Strategies in Retinal Vascular Diseases: A Lipid Target, Phosphatidylserine, and Annexin A5-A Future Theranostic Pairing in Ophthalmology.

Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of vascular endothelial growth factor (VEGF). Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signaling. This review explores the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. The clinical development status of Annexin A5 as a therapeutic and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular is described.

Time to initiate anti-vascular endothelial growth factor therapy and visual outcome in central retinal vein occlusion

This retrospective study aimed to investigate the progression of central retinal vein occlusion (CVO) prior to treatment initiation and its impact on prognosis. Of the 54 studied eyes with acute CVO, the average logMAR visual acuity (VA) at the initial visit was 0.65 ± 0.49 with an average time to treatment of 14.9 ± 14.5 days. VA at the initial treatment was identified as a stronger predictor of VA at the final visit compared to VA at the first visit or other factors. Patients who received treatment more than 28 days after the initial visit experienced a significant decline in VA compared to those treated within 28 days (0.21 ± 0.35 vs. 0.04 ± 0.13, p = 0.006). Additionally, patients who were treated between 15 and 28 days showed a greater decrease in VA compared to those treated within 14 days (0.12 ± 0.46 vs. 0.018 ± 0.02, p = 0.026). These findings from the current retrospective analysis suggesting that there is a possibility of VA decline at the initial treatment associating with worse prognosis even when treatment is administered within a month should be further investigated in the prospective study. Also, it may be crucial to consider frequent monitoring of acute CVO patients for initiating treatment at the optimal timing.

Investigation of choroidal structure changes after intravitreal anti-VEGF therapy for retinal vein occlusion.

We aimed to investigate the effect of retinal vein occlusion (RVO) on the posterior segment structures of the eye and its changes with intravitreal anti-Vascular Endothelial Growth Factor (VEGF) treatment. This prospective longitudinal study included 29 eyes of 29 patients with RVO (17 males and 12 females) followed for 6 months. The best corrected visual acuity (BCVA), macula, choroid ticknesses and choroidal vascularity index (CVI) obtained by spectral-domain optical coherence tomography were recorded at baseline and the first, third, and sixth months after the first injection. Results were compared with fellow eyes (non-affected eyes) and age- and sex-matched controls. BCVA increased significantly in the 6th month, more in the first month of injection (p < 0.05 for each). Central macular tickness, subfoveal choroid tickness, stromal and total area of choroid decreased significantly after injection (p < 0.05 for each). CVI values increased significantly, especially in the 1st month after injection (p < 0.05 for each). In eyes with Branch RVO, there was a significant decrease in the macular thickness of the occlusive areas with treatment, while there was no statistically significant change in the non-occlusive macular thickness. Observation of changes in choroidal structure may be useful to assess the activity of RVO and predict the efficacy of anti-VEGF therapy.

Study of serum vitamin D and homocysteine levels in patients with diabetic retinopathy and retinal vein occlusion

Study of serum vitamin D and homocysteine levels in patients with diabetic retinopathy and retinal vein occlusion

MFRP variations cause nanophthalmos in five Chinese families with distinct phenotypic diversity.

Nanophthalmos is a congenital ocular structural anomaly that can cause significant visual loss in children. The early diagnosis and then taking appropriate clinical and surgical treatment remains a challenge for many ophthalmologists because of genetic and phenotypic heterogeneity. The objective of this study is to identify the genetic cause of nanophthalmos in the affected families and analyze the clinical phenotype of nanophthalmos with MFRP gene variation (Microphthalmia, isolated; OMIM#611040 and Nanophthalmos 2; OMIM#609549, respectively). Comprehensive ophthalmic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. The normal protein structure was constructed using Alphafold. Mutant proteins were visualized using pymol software. Pathogenicity of identified variant was determined by in silico analysis and the guidelines of American College of Medical Genetics and Genomics (ACMG). The relationship between genetic variants and clinical features was analyzed. Five nanophthalmos families were autosomal recessive, of which four families carried homozygous variants and one family had compound heterozygous variants in the MFRP gene. Both family one and family three carried the homozygous missense variant c.1486G>A (p.Glu496Lys) in the MFRP gene (Clinvar:SCV005060845), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis. The proband of family one presented papilloedema in both eyes, irregular borders, thickened retinas at the posterior pole, tortuous and dilated retinal vessels, and indistinguishable arteries and veins, while the proband of family three presented uveal effusion syndrome-like changes in the right eye. In families one and 3, despite carrying the same gene variant, the probands had completely different clinical phenotypes. The homozygous nonsense variant c.271C>T (p.Gln91Ter) (Clinvar:SCV005060846) of the MFRP gene was detected in family 2, presenting shallow anterior chamber in both eyes, pigmentation of peripheral retina 360° from the equator to the serrated rim showing a clear demarcation from the normal retina in the form of strips. Family four proband carried the homozygous missense variant c.1411G>A (p.Val471Met) in the MFRP gene (Clinvar:SCV005060847), family five proband carried compound heterozygous missense variants c.1486G>A (p.Glu496Lys) and c.602G>T (p.Arg201Leu) in the MFRP gene (Clinvar:SCV005060848), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis, and they all presented clinically with binocular angle-closure glaucoma, family four also had retinal vein occlusion in the right eye during the follow-up. In this study, pathogenic variants of the MFRP gene were detected in five nanophthalmos families, including two novel variants. It also revealed a distinct phenotypic diversity among five probands harboring variants in the MFRP gene. Our findings extend the phenotype associated with MFRP variants and is helpful for ophthalmologists in early diagnosis and making effective treatment and rehabilitation strategies.

Concurrent Onset of Central Retinal Vein Occlusion and Inflammation of a Large Maxillary Odontogenic Cyst: Case Report and Analysis

Central retinal vein occlusion typically manifests in older individuals with underlying systemic pathology, leading to a spectrum of symptoms ranging from blurred vision to complete vision loss. While odontogenic infections are recognized for causing complications affecting the eye and vision, their potential role as an etiological factor in cases of sudden vision impairment merits consideration. This article presents a case involving central retinal vein thrombosis, wherein resolution was achieved through a combination of ophthalmic therapy and the surgical removal of a concurrently existing large inflamed odontogenic cyst located in the ipsilateral hemimaxilla. This case underscores the importance of recognizing odontogenic factors in the assessment of sudden vision impairment and the efficacy of a multidisciplinary therapeutic approach.

Fatty Acid-Binding Protein 4-Mediated Regulation Is Pivotally Involved in Retinal Pathophysiology: A Review.

Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member of this family of proteins that are expressed in adipocytes and macrophages, plays pivotal roles in the pathogenesis of various cardiovascular and metabolic diseases, including diabetes mellitus (DM) and hypertension (HT). Since significant increases in the serum levels of FABP4 were detected in those patients, FABP4 has been identified as a crucial biomarker for these systemic diseases. In addition, in the field of ophthalmology, our group found that intraocular levels of FABP4 (ioFABP4) and free fatty acids (ioFFA) were substantially elevated in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), for which DM and HT are also recognized as significant risk factors. Recent studies have also revealed that ioFABP4 plays important roles in both retinal physiology and pathogenesis, and the results of these studies have suggested potential molecular targets for retinal diseases that might lead to future new therapeutic strategies.

Deletion of myeloid HDAC3 promotes efferocytosis to ameliorate retinal ischemic injury

Ischemia-induced retinopathy is a hallmark finding of common visual disorders including diabetic retinopathy (DR) and central retinal artery and vein occlusions. Treatments for ischemic retinopathies fail to improve clinical outcomes and the design of new therapies will depend on understanding the underlying disease mechanisms. Histone deacetylases (HDACs) are an enzyme class that removes acetyl groups from histone and non-histone proteins, thereby regulating gene expression and protein function. HDACs have been implicated in retinal neurovascular injury in preclinical studies in which nonspecific HDAC inhibitors mitigated retinal injury. Histone deacetylase 3 (HDAC3) is a class I histone deacetylase isoform that plays a central role in the macrophage inflammatory response. We recently reported that myeloid cells upregulate HDAC3 in a mouse model of retinal ischemia-reperfusion (IR) injury. However, whether this cellular event is an essential contributor to retinal IR injury is unknown. In this study, we explored the role of myeloid HDAC3 in ischemia-induced retinal neurovascular injury by subjecting myeloid-specific HDAC3 knockout (M-HDAC3 KO) and floxed control mice to retinal IR. The M-HDAC3 KO mice were protected from retinal IR injury as shown by the preservation of inner retinal neurons, vascular integrity, and retinal thickness. Electroretinography confirmed that this neurovascular protection translated to improved retinal function. The retinas of M-HDAC3 KO mice also showed less proliferation and infiltration of myeloid cells after injury. Interestingly, myeloid cells lacking HDAC3 more avidly engulfed apoptotic cells in vitro and after retinal IR injury in vivo compared to wild-type myeloid cells, suggesting that HDAC3 hinders the reparative phagocytosis of dead cells, a process known as efferocytosis. Further mechanistic studies indicated that although HDAC3 KO macrophages upregulate the reparative enzyme arginase 1 (A1) that enhances efferocytosis, the inhibitory effect of HDAC3 on efferocytosis is not solely dependent on A1. Finally, treatment of wild-type mice with the HDAC3 inhibitor RGFP966 ameliorated the retinal neurodegeneration and thinning caused by IR injury. Collectively, our data show that HDAC3 deletion enhances macrophage-mediated efferocytosis and protects against retinal IR injury, suggesting that inhibiting myeloid HDAC3 holds promise as a novel therapeutic strategy for preserving retinal integrity after ischemic insult.

Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis.

To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. Prospero Registration Number CRD42021243185.

Optimizing open-angle glaucoma risk assessment in patients with retinal vein occlusions.

To evaluate factors associated with the diagnosis of open-angle glaucoma (OAG) after a retinal vein occlusion (RVO). Retrospective, cross-sectional study. Patients diagnosed with OAG after RVO were matched 2:1 with RVO patients without prior glaucoma. Logistic regression identified factors linked to OAG diagnosis. Of 1178 RVO patients without initial OAG, 51 (4.5%) were later diagnosed with OAG after an average of 5.5 ± 6.1 years. Screening tests for OAG were performed at a higher frequency in patients diagnosed with OAG compared with patients who never received this diagnosis (visual field [VF] testing 21.6% versus 10.8% (P = 0.073) and retinal nerve fiber layer [RNFL] imaging 52.9% versus 27.4% (P = 0.002), respectively). At the time of the first VF obtained after RVO, mean deviation averaged -10.3 dB in the affected eyes, compared with -5.0 dB in the fellow eyes (P < 0.001); in contrast, RNFL thickness was similar between eyes at the time of OAG diagnosis (72 µm versus 74 µm, P = 0.290). Predictive factors for OAG diagnosis included higher intraocular pressure (IOP) and cup-to-disc ratio (CDR) in the unaffected eye, and the absence of macular edema in the RVO-affected eye (R2 = 0.375, P < 0.001). OAG is a significant risk factor for RVO. Our study reveals a reciprocal relationship between RVO and the development of OAG, highlighting the need for glaucoma risk assessment in all patients with RVOs to avoid delays in diagnosis and vision loss from glaucoma.

Deciphering the interplay of gut microbiota and metabolomics in retinal vein occlusion.

Retinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.

Aflibercept in a real-world setting: the AURIGA study : 24-month results of the German cohort of treatment-naïve patients with macular edema following retinal vein occlusion receiving intravitreal aflibercept

AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2 mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO. Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2 mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month12 compared to baseline. Analyses were descriptive. Analysis included 130 patients with RVO (n = 61, 46.9% with central RVO, n = 69, 53.1% with branch RVO). The mean (±SD) time the RVO patients remained in the study was 18.4 ± 7.4months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month12 and +9.7 (6.1-13.3) at month24 (baseline VA 56.5 ± 18.9 letters). At 24months, 67% of RVO patients gained ≥5letters and 40% gained ≥15letters. The mean number of injections was 4.4 ± 1.3 up to month6, 6.2 ± 2.7 up to month12 and8.2 ± 4.5 up to month24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12months and -219µm (-263 to -175µm) at 24months (baseline CRT 507 ± 177 µm). The safety profile was consistent with that of previous studies. In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2 mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and areduction in CRT. These results were largely maintained over 24months despite the low injection frequency from month6.

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and consequently has enabled the introduction of new treatment methods. Moreover, artificial intelligence (AI) is likely to assist in selecting the best treatment option for patients in the near future. The aim of this comprehensive review is to re-evaluate the old but still relevant data on the RVO and confront them with new studies. The paper will provide a detailed overview of diagnosis, current treatment, prevention, and future therapeutic possibilities regarding RVO, as well as clarifying the mechanism of macular edema in this disease entity.

Increased risks of retinal vascular occlusion in patients with migraine and the protective effects of migraine treatment: a population-based retrospective cohort study

Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p < 0.001). The hazards of retinal vascular occlusion, RAO, and RVO were significantly greater in the migraine group (aHR, 1.69 [95% CI, 1.57, 1.83], 2.13 [95% CI, 1.84, 2.48] and 1.53 [95% CI, 1.40, 1.68], respectively). Risks of retinal vascular occlusion were significantly higher in migraine both with aura (MA) and without aura (MO) (aHR, 1.77 [95% CI, 1.58, 1.98], and 1.92 [95% CI, 1.64, 2.25]). Among patients with migraine, nonsteroidal anti-inflammatory drugs, propranolol, and flunarizine significantly reduce their risks of retinal vascular occlusion (aHR, 0.19 [95% CI, 0.16, 0.22], 0.73 [95% CI, 0.62, 0.86], 0.84 [95% CI, 0.76, 0.93]). Migraine, MA and MO are independently associated with higher risks of retinal vascular occlusion, RAO, and RVO.