Hemicentral retinal vein occlusion in a patient with a history of coronavirus disease 2019 infection: a case report and review of the literature.

BACKGROUND: Considering the various manifestations of coronavirus disease 2019 and its imperative importance in terms of the right clinical approach and early management, we sought to present a hemicentral retinal vein occlusion case, with a history of heterozygosity of methylenetetrahydrofolate reductase (MTHFR) genes and potential for clotting complications as a late manifestation of coronavirus disease 2019, and provide a brief review of reported retinal vein occlusion cases in patients with coronavirus disease 2019. CASE PRESENTATION: A 35-year-old Iranian patient presented with a visual impairment in the left eye 4 months after recovering from coronavirus disease 2019. He reported a mild blurring of vision in the same eye a few days after admission due to coronavirus disease 2019. The ophthalmic evaluation was compatible with hemicentral retinal vein occlusion. Systemic and laboratory workups were negative except for borderline protein C activity, homocysteine levels, and heterozygosity of MTHFR genes. The patient was scheduled to receive three monthly intravitreal antivascular endothelial growth factor injections. CONCLUSION: We present a case of inferior hemicentral retinal vein occlusion case with an MTHFR mutation with sequential loss of vision 4 months after coronavirus disease 2019 to make clinicians aware of the possibility of late ocular coronavirus disease 2019 manifestations.

Bilateral central retinal vein occlusion following COVID-19 vaccination: Cause or coincidence?

AIM: To report a case of sequential bilateral ischemic central retinal vein occlusion (CRVO) following the third dose of anti-COVID 19 vaccination. METHODS: Observational case report. RESULTS: A 73-year-old Caucasian male patient, with no known medical history, complained of sudden vision loss in his right eye (RE) 18 days following the third dose of Pfizer-BioNTech anti-COVID 19 vaccination. Ten days later, he suffered from sudden vision loss in his left eye (LE).Best-corrected visual acuity was limited to counting fingers at 50cm in both eyes.Fundus examination of both eyes revealed signs of ischemic central retinal vein occlusion (CRVO) with diffuse superficial and deep retinal hemorrhages in all four quadrants. Diagnosis was confirmed of fluorescein angiography.Optical coherent tomography (OCT) showed an ischemic hyperreflectivity and disorganization of the inner retinal layers in both eyes with significantly increased central macular thickness, associated to intraretinal fluid accumulation in LE.An urgent systemic assessment was requested. A mild hypertension was discovered and the rest of the work up was unremarkable. CONCLUSION: To our knowledge, we report the first case of bilateral CRVO in a healthy patient after anti-COVID 19 vaccination. CRVO occurred few days following third shot of vaccine followed by a sequential CRVO in the fellow eye in a patient with recently diagnosed very mild hypertension and no thrombo-embolic risk factors, strongly suggesting a relationship between both events. Nowadays, CRVO should be kept in mind as a potential side effect of Covid-19 vaccination and should be added to the spectrum of their ophthalmic complications.

PSORIASIS INCREASES RETINAL VEIN OCCLUSION RISK IN DIABETIC PATIENTS: A Nationwide Population-Based Study.

PURPOSE: The objective of this research was to explore how psoriasis is linked to the occurrence of retinal vein occlusion (RVO) in diabetic population. METHODS: This was a retrospective, nationwide, population-based cohort study that examined medical records from January 2009 to December 2012. The study focused on patients ≥20 years of age who had been diagnosed with Type 2 diabetes mellitus (DM). The authors compared the incidence rate of RVO between a group of patients with psoriasis and a group of patients without psoriasis until December 2018 in all subjects. RESULTS: Of the 2,745,689 Type 2 DM patients, 23,725 patients were classified in the psoriasis group and the rest of the 2,547,121 individuals in the control group. A total of 497 RVO cases occurred in the psoriasis group (3.14/1,000 person-years) and 42,388 RVO cases in the control group (2.44/1,000 person-years). According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly greater risk of developing RVO compared with control subjects (hazard ratio: 1.216, 95% confidence interval: 1.11-1.33) after adjustments for covariates. CONCLUSION: This study demonstrated that psoriasis was an independent risk factor for developing RVO in DM patients. Therefore, physicians need to be vigilant for the occurrence of RVO in DM patients who also have psoriasis.

Ocular manifestations of obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: The association of obstructive sleep apnea (OSA) with development of eye diseases is unclear. This current systematic review and meta-analysis attempts to summarize and analyze associations between OSA and ocular disorders in the literature. METHODS: PubMed, EMBASE, Google Scholar, Web Of Science, and Scopus databases were searched from 1901 to July 2022 in accordance with the Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA). Our primary outcome assessed the association between OSA and the odds of developing floppy eyelid syndrome (FES), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), keratoconus (KC), idiopathic intracranial hypertension (IIH), age-related macular degeneration (AMD), and central serous chorioretinopathy (CSR) through odds ratio calculated at the 95% confidence interval. RESULTS: Forty-nine studies were included for systematic review and meta-analysis. The pooled OR estimate was highest for NAION [3.98 (95% CI 2.38, 6.66)], followed by FES [3.68 (95% CI 2.18, 6.20)], RVO [2.71(95% CI 1.83, 4.00)], CSR [2.28 (95% CI 0.65, 7.97)], KC [1.87 (95% CI 1.16, 2.99)], glaucoma [1.49 (95% CI 1.16, 1.91)], IIH [1.29 (95% CI 0.33, 5.01)], and AMD [0.92 [95% CI 0.24, 3.58] All observed associations were significant (p < 0.001) aside from IIH and AMD. CONCLUSION: OSA is significantly associated with NAION, FES, RVO, CSR, KC, and glaucoma. Clinicians should be informed of these associations so early recognition, diagnosis, and treatment of eye disorders can be addressed in at-risk groups, and early referral to ophthalmic services is made to prevent vision disturbances. Similarly, ophthalmologists seeing patients with any of these conditions should consider screening and referring patients for assessment of possible OSA.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

RETINAL VASCULAR OCCLUSION AND COVID-19 DIAGNOSIS: A Multicenter Population-Based Study.

BACKGROUND: Several ocular diseases have been reported in patients with coronavirus disease 2019 (COVID-19), especially retinal vascular occlusion. This study aimed to examine the risk of retinal vascular occlusion after COVID-19 diagnosis. METHODS: This retrospective cohort study was based on 46 health care organizations in the United States using the TriNetX network. Individuals who had laboratory confirmation of COVID-19 from January 1, 2020, to December 31, 2021, were included. Multivariate analysis was adjusted on age, sex, race, and comorbidities, and hazard ratio was calculated using the Cox proportional hazard regression model. RESULTS: A total of 1,460,634 paired individuals were enrolled for analysis. Patients with COVID-19 had a significantly higher risk of branch retinal vein occlusion (hazard ratio 1.27, 95% confidence interval [CI] 1.04-1.52) than those without COVID-19. The cumulative incidence rate of branch retinal vein occlusion was also significantly higher in patients with COVID-19 compared with those without COVID-19 (log-rank P = 0.014). Within 12 weeks after COVID-19 diagnosis, the transient effect of central retinal vein occlusion (hazard ratio 1.59, 95% confidence interval 1.15-2.17) and branch retinal vein occlusion (hazard ratio 2.11, 95% confidence interval 1.51-2.95) were observed. CONCLUSION: This large-scale multicenter study demonstrated that retinal vein occlusion may be associated with COVID-19.

Neurofibromatosis Type 1 Vasculopathy Presenting as Branch Retinal Vein Occlusion: Case Report and Review of the Literature

Systemic vascular occlusive disease associated with neurofibromatosis type 1 (NF1) has been reported in the aortic, cerebral, renal, celiac, and mesenteric vessels and is referred to as NF1 vasculopathy. Although retinal vascular involvement in patients with NF1 usually manifests as retinal capillary hemangiomatosis, a few cases of NF1 with retinal vascular occlusive disease have also been described. Here, we report a 2-year-old girl with NF1 who presented with branch retinal vein occlusion and peripheral retinal ischemia secondary to NF1. This case demonstrates that NF1-related retinal occlusive vasculopathy may occur in very young patients and that detailed fundus examination with fluorescein angiography is necessary in all patients with NF1.

Retinal vascular occlusion risks during the COVID-19 pandemic and after SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018-2019 and 2020-July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018-2019 and 2020-2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018-2019 and 2020-2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence.

Case Report: Branch Retinal Vein Occlusion Post-mRNA SARS-CoV-2 (COVID-19) Vaccination.

SIGNIFICANCE: Systemic thromboembolic complications are well documented to be associated with coronavirus disease 2019 (COVID-19); however, there have been a growing number of reports regarding ocular complications stemming from COVID-19 vaccinations. This case illustrates a clear temporal and possible causal relationship of COVID-19 vaccination with an ocular microvascular disorder, namely, retinal vein occlusion. PURPOSE: This study aimed to report a case of inferotemporal branch retinal vein occlusion after messenger RNA Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CASE REPORT: A middle-aged woman developed right eye central scotoma 2 days after COVID-19 vaccination. She had transient hypertension during the first 2 days post-vaccination. A decrease in visual acuity (6/18) was documented. Initial retinal findings included flame-shaped hemorrhages and cotton-wool spots along inferotemporal branch retinal vessels. Optical coherence tomography revealed right eye cystoid macular edema. Laboratory investigation revealed mildly raised erythrocyte sedimentation rate and C-reactive protein. Other systemic examinations were unremarkable. She was treated for right eye inferotemporal branch retinal vein occlusion with cystoid macular edema and was given intravitreal anti-vascular endothelial growth factor monthly in three doses. Her visual acuity improved to 6/6 with resolved cystoid macular edema. CONCLUSIONS: This case illustrates a clear temporal and possible causal relationship between COVID-19 vaccination and retinal vein occlusion. Post-vaccination transient hypertension or the immunological and inflammatory response to the vaccine may have contributed to the venous occlusive event in this case. Eye care providers should remain aware of this possibility. The effectiveness of intravitreal anti-vascular endothelial growth factor for the treatment of macular edema secondary to branch retinal vein occlusion was demonstrated in this patient.

Retinal vein occlusion in the general population after COVID-19 vaccination and infection / Obstrucción venosa retiniana en la población general después de la vacunación y de la COVID-19

Introduction Retinal vein occlusion (RVO) is mostly a consequence of vascular risk factors (VRF). COVID-19 vaccines have been related to vascular and thrombotic events (VTE). Objective To assess the RVO incidence in the general population in our health area and the possible relation with COVID-19 infection and vaccination. Methods Demographic features, classic VRF, thrombophilia data, COVID-19 status, and Framingham risk score were collected prospectively. Results 472 consecutive patients studied over 13 years with RVO were included (Valdecilla Cohort). Classic VRFs were present in 90%, antiphospholipid syndrome in 12.3%, and genetic thrombophilia in 13.5%. Ninety-one percent of RVO patients were vaccinated and 6.8% suffered COVID-19 infection. In the cohort, no patient had a new RVO after vaccination or infection. In the general population, 20 subjects had RVO after receiving the vaccine (0.006%). Overall, 8 cases occurred in the first-month post-vaccination and 12 after 30 days. In the early and late groups, there are 3 and 4 patients respectively, with a low-intermediate risk Framingham score. Twenty-nine patients in the cohort suffered SARS-CoV-2 infection, twenty-seven of them had RVO before infection. Two patients with low-risk Framingham scores had RVO after infection, one of them early (<1 month). Conclusion Vaccination and COVID-19 might be involved in the development of RVO in some cases, mainly in patients without VRF, thrombophilia, or chronic inflammatory conditions and with a lower Framingham score, especially in the first month after vaccination or infection (AU)

Introducción La oclusión venosa retiniana (OVR) es principalmente una consecuencia de los factores de riesgo vascular (FRV). Las vacunas contra la COVID-19 se han relacionado con eventos vasculares y trombóticos (EVT). Objetivo Evaluar la incidencia de OVR en la población general de nuestra área de salud y su posible relación con la COVID-19 y la vacunación. Métodos Se recopilaron prospectivamente las características demográficas, FRV clásicos, datos sobre trombofilia, padecimiento de la COVID-19 y puntuación de riesgo de Framingham. Resultados Se incluyeron 472 pacientes consecutivos con OVR, estudiados durante 13 años (Cohorte Valdecilla). Los FRV clásicos estaban presentes en el 90%, el síndrome antifosfolípido en el 12,3% y la trombofilia genética en el 13,5% de los casos. El 91% de los pacientes con OVR recibieron la vacuna frente a la COVID-19 y el 6.8% sufrió la infección. En la cohorte, ningún paciente tuvo una nueva OVR después de la vacunación o de la infección. En la población general, 20 sujetos presentaron OVR después de recibir la vacuna (0,006%). En general, 8 casos ocurrieron en el primer mes después de la vacunación y 12 después de 30 días. En los grupos precoz y tardío, 3 y 4 pacientes respectivamente, presentaban una puntuación de Framingham de riesgo bajo o intermedio. Veintinueve pacientes de la cohorte sufrieron infección por SARS-CoV-2 y 27 de ellos tuvieron una OVR antes de ésta. Dos pacientes con puntuaciones de Framingham de bajo riesgo presentaron una OVR después de la infección, uno de ellos precozmente (<1 mes). Conclusiones La vacunación y la COVID-19 podrían estar involucradas en el desarrollo de OVR en algunos casos, principalmente en pacientes sin FRV, trombofilia o procesos inflamatorios crónicos y con una puntuación de Framingham más baja, especialmente en el primer mes después de la vacunación o de la infección (AU)

The Incidence, Time to Development, and Risk Factors for Fellow Eye Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: Little is known about factors affecting risk or time to development of fellow eye retinal vein occlusion (RVO). The purpose of this study was to examine the incidence and risk factors for fellow eye RVO. PATIENTS AND METHODS: This was a retrospective case-control study comparing unilateral and fellow eye RVO patients. This study was exempt by the Cleveland Clinic Institutional Review Board. RESULTS: Out of 1,083 patients, fellow eye RVO had a cumulative incidence of 3.6% (95% CI 2.61, 4.94) with a median time to development of 18 months (95% CI 6.0, 28.0). Fellow eye disease was associated with multiple characteristics including chronic kidney disease (odds ratio [OR] 3.78, 95% CI 1.89 to 7.55) and diabetic retinopathy (3.18, 1.57 to 6.44). CONCLUSION: While fellow eye RVO is relatively rare, it typically occurs within the first few years following initial diagnosis. Multiple characteristics were associated with fellow eye disease and time to onset. [Ophthalmic Surg Lasers Imaging Retina 2023;54:471-476.].

Retinal vein occlusion in the general population after COVID-19 vaccination and infection.

INTRODUCTION: Retinal vein occlusion (RVO) is mostly a consequence of vascular risk factors (VRF). COVID-19 vaccines have been related to vascular and thrombotic events (VTE). OBJECTIVE: To assess the RVO incidence in the general population in our health area and the possible relation with COVID-19 infection and vaccination. METHODS: Demographic features, classic VRF, thrombophilia data, COVID-19 status, and Framingham risk score were collected prospectively. RESULTS: 472 consecutive patients studied over 13 years with RVO were included (Valdecilla Cohort). Classic VRFs were present in 90%, antiphospholipid syndrome in 12.3%, and genetic thrombophilia in 13.5%. Ninety-one percent of RVO patients were vaccinated and 6.8% suffered COVID-19 infection. In the cohort, no patient had a new RVO after vaccination or infection. In the general population, 20 subjects had RVO after receiving the vaccine (0.006%). Overall, 8 cases occurred in the first-month post-vaccination and 12 after 30 days. In the early and late groups, there are 3 and 4 patients respectively, with a low-intermediate risk Framingham score. Twenty-nine patients in the cohort suffered SARS-CoV-2 infection, twenty-seven of them had RVO before infection. Two patients with low-risk Framingham scores had RVO after infection, one of them early (<1 month). CONCLUSIONS: Vaccination and COVID-19 might be involved in the development of RVO in some cases, mainly in patients without VRF, thrombophilia, or chronic inflammatory conditions and with a lower Framingham score, especially in the first month after vaccination or infection.

DeepDrRVO: A GAN-auxiliary two-step masked transformer framework benefits early recognition and differential diagnosis of retinal vascular occlusion from color fundus photographs.

Retinal vascular occlusion (RVO) are common causes of visual impairment. Accurate recognition and differential diagnosis of RVO are unmet medical needs for determining appropriate treatments and health care to properly manage the ocular condition and minimize the damaging effects. To leverage deep learning as a potential solution to detect RVO reliably, we developed a deep learning model on color fundus photographs (CFPs) using a two-step masked SwinTransformer with a Few-Sample Generator (FSG)-auxiliary training framework (called DeepDrRVO) for early and differential RVO diagnosis. The DeepDrRVO was trained on the training set from the in-house cohort and achieved consistently high performance in early recognition and differential diagnosis of RVO in the validation set from the in-house cohort with an accuracy of 86.3%, and other three independent multi-center cohorts with the accuracy of 92.6%, 90.8%, and 100%. Further comparative analysis showed that the proposed DeepDrRVO outperforms conventional state-of-the-art classification models, such as ResNet18, ResNet50d, MobileNetv3, and EfficientNetb1. These results highlight the potential benefits of the deep learning model in automatic early RVO detection and differential diagnosis for improving clinical outcomes and providing insights into diagnosing other ocular diseases with a few-shot learning challenge. The DeepDrRVO is publicly available on https://github.com/ZhouSunLab-Workshops/DeepDrRVO.

Central Retinal Vein Occlusion after COVID-19 Infection.

INTRODUCTION: Central retinal vein occlusions are not well-known complications of SARS-CoV-2 infection. We describe a case of central retinal vein occlusion secondary to COVID-19, and a review of the literature was performed. HISTORY AND SIGNS: A 47-year-old woman with no underlying ocular or medical condition presented to the hospital complaining about sudden onset of multiple scotomas in her left eye. A COVID-19 infection was confirmed 2 days previously by a PCR test that was performed 2 days after the onset of symptoms. Medical history revealed no risk factors and no oral contraception. Her best-corrected visual acuity was 1.0 in the right eye and 0.04 in the left eye. Clinical exam showed a left relative afferent pupillary defect and a nasally localized papilledema on fundoscopy of the left eye. Multiple dot and blot hemorrhages were also present. Optical coherence tomography revealed cystoid macular edema and paracentral acute middle maculopathy. The results of the fluoresceine angiography were consistent with central retinal vein occlusion. Laboratory workup later revealed an elevated fibrinogen level, corresponding to the COVID-19-induced hypercoagulable state. No other prothrombotic conditions were found. The patient immediately received an intravitreal injection of Lucentis (ranibizumab) after diagnosis. Complete resolution of the retinal hemorrhages and papilledema was observed 1.5 months after treatment and the final visual acuity was 1.25 in the left eye. CONCLUSION: Coagulation abnormalities are frequently observed in infectious diseases such as COVID-19 infection and the resulting prothrombotic state can sometimes lead to retinal vascular complications, including central retinal vein occlusion, irrespective of the presence of other classical risk factors. The consideration of this information could help clinicians establish a prompt diagnosis and therefore appropriate treatment, which could hopefully lead to complete healing of retinal lesions.

Mendelian randomization indicates a causal contribution of type 2 diabetes to retinal vein occlusion.

Background: Retinal vein occlusion (RVO) is a common retinal vascular disease that can cause severe visual impairment. Many observational studies have shown that type 2 diabetes (T2DM) is associated with RVO, but it remains unknown if the association is causal. The present study aimed to perform Mendelian randomization (MR) analyses to evaluate the causal contribution of genetically predicted T2DM to RVO. Methods: We obtained summary-level data from a genome-wide association study meta-analysis including 48,286 cases and 250,671 controls for T2DM and from a genome wide association study of 372 cases and 182,573 controls in the FinnGen project for RVO. To verify the robustness of the results, an independent validation dataset for T2DM (12,931 cases and 57,196 controls) was used. In addition to the main MR analysis using the inverse variance weighted (fixed effect) approach, sensitivity analyses and multivariable MR adjusting for common risk factors of RVO were conducted. Results: Genetically predicted T2DM was found to be causally associated with RVO risk (odds ratio (OR)=2.823, 95% confidence interval (CI): 2.072-3.847, P=4.868×10-11). This association was supported by sensitivity analyses using the weighted median (OR=2.415, 95% CI: 1.411-4.132, P=1.294×10-3), weighted mode (OR=2.370, 95% CI: 1.321-4.252, P=5.159×10-3), maximum likelihood (OR=2.871, 95% CI: 2.100-3.924, P=3.719×10-11), MR-PRESSO (OR=2.823, 95% CI: 2.135-3.733, P=5.150×10-10), and MR-Egger (OR=2.441, 95% CI: 1.149-5.184, P=2.335×10-2) methods. In addition, this association persisted in multivariable MR after accounting for common RVO risk factors (OR=1.748, 95% CI: 1.238-2.467, P=1.490×10-3). The MR analyses using the validation dataset obtained consistent results. Conclusion: This study indicates that genetically predicted T2DM may have a causal contribution to RVO. Future studies are required to elucidate the underlying mechanisms.