Ischemic and Inflammatory Ocular Adverse Events Following Different Types of Vaccination for COVID-19 and Their Incidence Analysis.

PURPOSE: To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination. METHODS: Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency. RESULTS: Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine. CONCLUSIONS: OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.

CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH USE OF AMYL NITRITE "POPPERS".

PURPOSE: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." METHODS: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. RESULTS: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. CONCLUSION: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Management of macular oedema due to retinal vein occlusion: An evidence-based systematic review and meta-analysis.

BACKGROUND: Central retinal vein occlusion and branch retinal vein occlusion are common causes of visual loss due to associated macular oedema. The aim of this review was to assess the effectiveness of interventions improving vision and treating macular oedema in central retinal vein occlusion and branch retinal vein occlusion. METHODS: Medical search engines and clinical trial registries were systematically searched. Randomised clinical trials with ≥90 eyes and real-world outcome studies with ≥100 eyes each with ≥6 months follow-up were included. RESULTS: There were 11 randomised controlled trials evaluating treatments for central retinal vein occlusion which met the inclusion criteria and 10 for branch retinal vein occlusion. There were 10 real world outcome studies of central retinal vein occlusion and 5 real world outcome studies of branch retinal vein occlusion. Meta-analysis was performed on studies that met the defined inclusion criteria. Main outcomes were change in visual acuity at 6-, 12-, 24- and 36 months by treatment. CONCLUSIONS: Intravitreal anti-vascular endothelial derived growth factor is recommended as first line treatment over intravitreal corticosteroid due to its effectiveness and lower rate of ocular adverse events. Best outcomes are achieved when intravitreal treatment is started early. Macular laser may have an adjunctive role in branch retina vein occlusion but not central retinal vein occlusion.

Multiple sclerosis and glatiramer acetate: Risk factors for central retinal vein occlusion?

Multiple sclerosis may present an increased risk for venous thromboembolism. Ophthalmological symptoms include loss of vision, visual field loss, changes in color vision, diplopia and nystagmus. First-line treatments for multiple sclerosis are beta-interferon, glatiramer acetate, dimethyl fumarate and teriflunomide. To the best of our knowledge, no ophthalmologic side effects have been reported with glatiramer acetate. We present a woman with multiple sclerosis on glatiramer acetate therapy with a central retinal vein occlusion in the absence of other risk factors.

Branch retinal vein occlusion secondary to hormone replacement therapy in a transgender woman.

PURPOSE: To report a case of branch retinal vein occlusion (BRVO) in a transgender woman having undergone hormone replacement therapy. METHODS: Observational case report. RESULTS: A 44-year-old transgender woman on hormone replacement therapy with transdermal estradiol gel for the past 6 years was referred for sudden loss of vision and metamorphopsia in her left eye (LE) for the past 3 weeks. Best-corrected visual acuity (BCVA) was 20/20 in her right eye (RE) and 20/40 in her LE. Dilated fundus examination showed deep flame-shaped hemorrhages, cotton wool spots, and arteriovenous crossing changes. Spectral-domain optical coherence tomography (SD-OCT, Spectralis; Heidelberg Engineering, Heidelberg, Germany) showed retinal edema in the superonasal perifoveal area. Optical coherence tomography angiography (OCTA PlexElite, Carl Zeiss Meditec, Inc, Dublin, CA) revealed the presence of areas of non-perfusion, disorganization of the capillary network and capillary ectasia and dilation. The patient was treated with 3 monthly intravitreal injections of aflibercept. Three-month follow up revealed complete resolution of the macular edema, with BCVA having improved to 20/20 in the LE. CONCLUSION: As estrogen increases cardiovascular risk when used in hormone replacement therapy, RVO is a complication that must be taken into account by clinicians, especially in transgender women (male-to-female) who are more at risk.

Bilateral Central Retinal Vein Occlusion Associated with Axitinib Therapy: A Case Report.

PURPOSE: To describe a case of retinal vascular occlusion and cerebrovascular accident following axitinib therapy. METHODS: A retrospective chart review. RESULT: A 65-year-old gentleman with a history of renal cell carcinoma and subsequent metastases to the brain was on axitinib at an oral daily dose of 10 mg. The patient reported a loss in vision in the right, followed by the left eye, and suffered an episode of cerebrovascular accident. Retinal examination revealed right eye optic nerve pallor with sclerosed vessels, possibly sequelae of central retinal vein occlusion, and left eye showed multiple retinal hemorrhages in all quadrants with macular edema, suggestive of central retinal vein occlusion. He was not a known hypertensive, his renal carcinoma was in remission, and his other systemic parameters were within acceptable limits. CONCLUSIONS: Axitinib can cause retinal vein occlusions, and clinicians, both oncologists, and ophthalmologists need to be aware of this rare but potentially blinding side effect.

SCORE2 Report 20: Relationship of Treatment Discontinuation With Visual Acuity and Central Subfield Thickness Outcomes.

PURPOSE: To investigate the relationship of anti-vascular endothelial growth factor (anti-VEGF) treatment discontinuation with baseline factors and outcomes in eyes treated initially with aflibercept or bevacizumab for macular edema from central or hemiretinal vein occlusion. DESIGN: Long-term follow-up after a randomized clinical trial from 64 US centers. METHODS: Analysis included 150 SCORE2 Month 60 completers classified into 3 groups: discontinued treatment early, treated intermittently, and treated continuously. Outcomes included visual acuity (VA) and central subfield thickness (CST). RESULTS: Patients who discontinued treatment early were younger (60.9 years, vs 66.7 and 70.5 for the treated intermittently and treated continuously groups; P = .001), and 17.4% were Black, compared to 19.5% and 4.7% for the treated intermittently and treated continuously groups (P = .006). At Month 60, the discontinued treatment early group had a higher proportion with complete resolution of macular edema (69.6%) than those treated intermittently (15.0%) and treated continuously (15.7%) (P < .001). Least-squares means analyses over follow-up demonstrated that the discontinued treatment early group had a lower mean CST (257 µm) than the treated intermittently (CST = 303 µm, P = .02) and treated continuously (CST = 300 µm, P = .01) groups. CONCLUSIONS: Compared to those treated continuously, those who discontinued treatment early were younger and more likely Black. The discontinued treatment early group had a higher proportion with complete resolution of macular edema at Month 60, and a lower mean CST over follow-up, but not better VA, than the treated continuously and treated intermittently groups. Results support the need for continued monitoring and individualized treatment for patients treated with anti-VEGF for macular edema from central or hemiretinal vein occlusion.

Retinal venous occlusion in a child following Corbevax COVID-19 vaccination.

A 13-year-old boy developed painless diminution of vision in left eye 15 days after taking first dose of coronavirus disease 2019 (COVID-19) vaccine (Corbevax). Fundus and fluorescein angiography revealed central retinal vein occlusion in the left eye. Blood investigations were noncontributory. He was administered three doses of pulse corticosteroids followed by a tapering dose of oral corticosteroids. Retinal vascular occlusion can occur following COVID-19 vaccination in children, and early and aggressive systemic anti-inflammatory therapy can be helpful.

Prognostic Factor Study of Macular Edema Recurrence in Retinal Vein Occlusion after Conbercept Treatment: A Post Hoc Analysis of the FALCON Study.

Objective: The study was aimed at exploring the potential predictive factors associated with the recurrence of macular edema (ME) secondary to vein occlusion (RVO) after intravitreal antivascular endothelial growth factor (VEGF) loading treatment in the FALCON study. Methods: This is a post hoc analysis of 30 patients with central RVO and 30 patients with branch RVO. All patients received a monthly administration of intravitreal conbercept during the 3-month loading phase and pro re nata (PRN) treatment during the 6-month follow-up period. Based on the recurrence of ME at the first follow-up visit, patients were classified into the recurrence group or nonrecurrence group. The primary endpoint was to explore the risk factors for recurrence among baseline characteristics, fluorescein angiography (FA) patterns, and optical coherence tomography (OCT). Results: In general, 38 patients (64.4%) experienced ME recurrence at the first follow-up visit (3 months), regardless of disease type (p = 0.32). Significant improvements in VA were noted in both the nonrecurrence and recurrence groups (p < 0.001), however, without significant between-group differences (p = 0.1). A significant reduction in CRT in both groups (p < 0.001) was identified, and patients without recurrence showed a greater reduction in CRT compared with those with recurrence (p < 0.001). In addition, logistic regression analyses indicated the corrections of ME recurrence with baseline macular volume and the disruption of the outer limiting membrane at the fovea. Conclusion: This study suggested that OCT parameters, including baseline macular volume and outer limiting membrane disruption, and reduction in CRT after loading therapy were more predictive of ME recurrence than FA patterns or visual changes following conbercept loading therapy.

COVID-19 AdenoviralVector Vaccine and Central Retinal Vein Occlusion.

PURPOSE: The purpose of this article is to report a case of sudden onset ischemic retinal central vein occlusion after a second dose of COVID-19 adenoviral vector vaccine. CASE REPORT/OBSERVATIONS: A 54-year-old woman with systemic arterial hypertension developed ischemic central retinal vein occlusion in her right eye on day 2 after the second dose of COVID-19 adenoviral vector vaccine ChAdOx1 nCoV-19/ AZD1222, Oxford-AstraZeneca. CONCLUSION: Adenoviral vector vaccine promotes both cellular and humoral immune responses, increasing the level of inflammatory cytokines. These cytokines are the same implied in the possible pathogenesis of central retinal vein occlusion. Subsequently, we recommend informing patients at risk of possible ocular adverse events, which require urgent evaluation.

Lack of predictive value of retinal oxygen saturation for visual outcome after angiostatic treatment of branch retinal vein occlusion.

PURPOSE: Previous studies have shown that the retinal oxygen saturation in central retinal vein occlusion treated with anti-VEGF compound has no predictive value for visual outcome after 12 months. It is of interest to evaluate whether this conclusion is similar for patients with branch retinal vein occlusion among whom only some patients are treated. METHODS: Retinal oxygen saturation, visual acuity and central retinal thickness were studied at the time of referral and after six and 12 months in 111 patients successively referred to the Department of Ophthalmology, Aarhus University Hospital, with a venous occlusion affecting branches peripheral from the central retinal venule. The predictive value of the oxygen saturation at referral was investigated in treated and untreated patients. RESULTS: Seventy-three patients with visual acuity between 35 and 70 ETDRS letters at referral were treated with intravitreal injection of anti-VEGF compound. Over 12 months, the venous oxygen saturation improved in parallel with central retinal thickness and visual acuity but had no predictive value for visual outcome. In 12 untreated patients with visual acuity >70 ETDRS letters, younger age and high oxygen saturation at the time of referral were positive predictors for the visual outcome after 12 months. CONCLUSION: Oxygen saturation, visual acuity and central retinal thickness improve in parallel during treatment of branch retinal vein occlusion with intravitreal anti-VEGF medication. Retinal oximetry at referral cannot predict visual acuity after 12 months in treated patients but may perhaps become a tool for predicting the visual prognosis in a subgroup of patients where treatment is omitted because of a too high visual acuity at the time of diagnosis of the disease.