Foveal Damage Due to Subfoveal Hemorrhage Associated with Branch Retinal Vein Occlusion

To investigate the functional and morphologic prognoses of eyes with subfoveal hemorrhage from acute branch retinal vein occlusion (BRVO), and to examine the effect of intravitreal ranibizumab injection (IVR) on these prognoses, we assessed 81 eyes with acute BRVO, of which 38 did not receive IVR [IVR(-) group], and 43 were treated with IVR [IVR(+) group] for macular edema. The foveal morphologic changes were examined via optical coherence tomography (OCT). At initial examination, 63 eyes exhibited subfoveal hemorrhage. At final examination, the defect lengths in the foveal external limiting membrane (ELM) and ellipsoid lines in these eyes were longer, and final VA was significantly poorer, compared with eyes without subfoveal hemorrhage. In comparisons between the final measurements in eyes with subfoveal hemorrhage in the IVR(-) and IVR(+) groups, while there were no differences in initial ocular conditions, final VA was significantly better in the IVR(+) group. The defects in the ELM and ellipsoid lines in the IVR(+) group were shorter than those of the IVR(-) group (p = 0.002 in both). Final VA was correlated with the defect lengths of foveal ELM and ellipsoid lines in both the IVR(-) and IVR(+) groups (both p < 0.001). In addition, the defect lengths of foveal ELM and ellipsoid lines were closely correlated with the duration of subfoveal hemorrhage (both p < 0.001). BRVO-associated subfoveal hemorrhage caused damage to the foveal photoreceptors, and visual dysfunction. However, IVR improved these prognoses, by accelerating the absorption of the subfoveal hemorrhage.     

Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion

Objective

To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO).

Subjects and Methods

We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean ± standard deviation age was 69.1 ± 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10° was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined.

Results

One month after IVB, the BCVA improved significantly from 0.56 ± 0.27 logMAR units to 0.32 ± 0.28 logMAR units, and the CMT from 611.4 ± 209.3 μm to 258.7 ± 64.0 μm (P <0.05). The AT improved significantly from 17.9 ± 5.3 dB to 21.2 ± 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month.

Conclusion

These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case.     

视网膜静脉阻塞与颈动脉狭窄的相关性研究

目的:探究视网膜静脉阻塞与颈动脉狭窄的相关性研究,并为其临床检测、治疗与预后提供参考。方法:选择我院55例视网膜静脉阻塞患者(55只眼)为研究组,对其裸眼视力、矫正视力、眼压、眼底血管荧光造影(FFA)等检查资料进行分析,并进行多普勒彩超检查,记录其颈动脉狭窄情况,并对两种疾病之间的关系进行分析。同时选取55例健康人作为对照组。结果:研究组55例患者确诊为视网膜静脉阻塞(RVO),多普勒结果显示患者患侧与健侧劲动脉血流动力学各项差异不明显(P0.05);其IMT值较之对照组显著增高(P0.05);其PSV与EDV值有所降低,差异具有统计学意义(P0.05)。结论:视网膜静脉阻塞患者大多存在颈动脉狭窄,因此检测颈动脉血流动力学对于诊断与预防视网膜静脉阻塞有着重要作用。     

Investigation of Retinal Morphology Alterations Using Spectral Domain Optical Coherence Tomography in a Mouse Model of Retinal Branch and Central Retinal Vein Occlusion

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.     

Differences in Aqueous Concentrations of Cytokines in Macular Edema Secondary to Branch and Central Retinal Vein Occlusion

Purpose

This study investigates the differential aqueous concentrations of interleukin 6, 8, 1β (IL-6, IL-8, IL-1β, respectively), serum amyloid A (SAA), transforming growth factor (TGF)-β, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in eyes with macular edema as a result of a branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

Principal Findings

Significantly higher concentrations of IL-6, IL-8, IL-1β, TGF-β, bFGF, SAA, and VEGF were found in the aqueous humor of CRVO and BRVO patients than in the aqueous humor of control patients. A significant correlation was observed between the concentration of bFGF and the inner central macular thickness (CMT) of BRVO patients (r = 0.688; P = 0.02). A significant correlation was observed between the concentration of SAA and both the full and outer CMT of the ischemic group (r = 0.545 and 0.683, respectively; P = 0.04 and 0.01, respectively). In the non-ischemic group, the level of IL-6 was significantly associated with inner CMT (r = 0.560; P = 0.03). The full and outer CMT was significantly reduced in CRVO patients when compared with BRVO patients (P = 0.02 and 0.02, respectively) after injection of intravitreal bevacizumab (IVB) at 4 weeks.

Significance

Serum amyloid A as a major protein involved in the acute and chronic stages of inflammation, and IL-6 and bFGF were significantly associated with the extent of macular edema in patients with RVO. Besides VEGF, other inflammatory cytokines and angiogenesic factors may be associated with RVO. This finding may have implications for the medical treatment of RVO.     

Efficacy and Safety of Intravitreal Therapy in Macular Edema Due to Branch and Central Retinal Vein Occlusion: a Systematic Review

Background

Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO.

Methods

And Findings: MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated.

Efficacy: CRVO

Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections).

BRVO

Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications.

Safety

Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events.

Conclusions

Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.     

抗VEGF药物联合532 激光治疗视网膜中央静脉阻塞的疗效分析

目的:探讨抗VEGF药物联合532激光治疗视网膜中央静脉阻塞的疗效。方法:选取60例患视网膜中央静脉阻塞患者,年龄38-65岁,研究组(31例)采用抗VEGF药物联合532激光治疗,对照组(29例)单纯给予激光治疗。监测患者治疗前,治疗后3个月的视力,黄斑中心凹厚度(Central macular thickness,CMT)以及治疗后3个月的治疗结果,对联合治疗与单纯激光方式的疗效进行对比。结果:治疗后3个月,研究组有效率明显高于对照组(P0.05)。与治疗前相比,研究组治疗后3个月,视力改善情况较明显(P0.05),且改善幅度大于对照组(P0.05)。对照组治疗后3个月,视力有了小幅度改善,然而与治疗前相比,差异没有统计学意义(P0.05)。治疗前,两组CMT相比,差异没有统计学意义(P0.05)。治疗后3个月,两组CMT均有明显改善,且研究组改变情况优于对照组(P0.05)。所有患者在治疗后3个月内均未严重并发症。结论:抗VEGF药物联合532激光治疗视网膜中央静脉阻塞,可以显著提高患者视力和治疗有效率,降低黄斑水肿,新生血管等并发症发生率,并且不会引起其他并发症。     

Antiphospholipid Antibody and Risk of Retinal Vein Occlusion: A Systematic Review and Meta-Analysis

Background

Retinal vein occlusion (RVO) is a common retinal vascular disease and it is one of the most frequently reported causes of visual damage and blindness in the elderly. The current study investigated the potential association between antiphospholipid antibodies (APLA) and RVO risk by conducting a meta-analysis of case–control studies.

Methods

A systematic literature search of Pubmed and Embase databases was conducted in August 1^st, 2014. Odds ratios (ORs) were used to evaluate the associations between APLA and the incidence of RVO. A random-effects model was obtained for the quantitative synthesis.

Results

A total of 11 studies were included in this meta-analysis. A meta-analysis of all studies assessing the risk of RVO revealed that APLA was associated with a statistically increased risk of RVO incidence (OR = 5.18, 95% CI = [3.37, 7.95]). The association between anticardiolipin antibodies (ACA) and the risk of RVO was significant (n =8, OR = 4.59, 95% CI = [2.75, 7.66]). However, the association between lupus anticoagulants (LA) and risk of RVO was non-significant (n = 5, OR = 3.90, 95% CI = [0.99, 15.37]). No significant publication bias was found in the 11 selected studies.

Conclusion

APLA was significantly associated with the risk of RVO. Advanced analyses showed that ACA rather than LA affected the risk of RVO. Additional well-designed and well-conducted epidemiological studies are required to further our understanding of the relationship between APLA and RVO risk.     

Increased Expression of Angiogenic and Inflammatory Proteins in the Vitreous of Patients with Ischemic Central Retinal Vein Occlusion

BackgroundCentral retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO.MethodsVitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray.ResultsExpression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE).ConclusionProteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.     

氩激光光凝建立兔视网膜静脉阻塞模型及其评价

目的制备视网膜中央静脉阻塞的动物模型,为视网膜中央静脉阻塞疾病的研究提供稳定的模型。方法采用氩激光直接光凝法封闭兔眼视网膜静脉建立视网膜静脉阻塞模型,利用HE染色法观察正常兔及造模后3周兔视网膜组织中视网膜新生血管的增生情况,利用免疫组化法观察正常兔及造模后3周兔视网膜组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,并检测造模前及造模后3周闪光视网膜电流图(flash electroretinogram,FERG)。结果兔视网膜静脉阻塞(retinal vein occlusion,RVO)眼可见明显的视网膜新生血管增生,缺血视网膜及新生血管组织中VEGF不同程度表达增强,FERG-b波的振幅明显下降(P<0.01)。结论采用氩激光直接光凝法建立视网膜静脉阻塞模型是成功的。     

A Meta-Analysis of Anti-Vascular Endothelial Growth Factor Remedy for Macular Edema Secondary to Central Retinal Vein Occlusion

Background

Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO.

Methods

Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. N_fs (called fail-safe number) was calculated to evaluate the publication bias.

Results

We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43–9.23; P<0.00001; I² = 59%, 95% CI: 1.60–3.49; P<0.0001; I² = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43–21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55–16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001).

Conclusions

Our results showed that anti-VEGF agents were superior to placebo in CRVO-ME treatment with no statistically significant AEs, especially in younger people and for ischemic type.     

视网膜激光光凝治疗视网膜静脉阻塞疗效及对IOP、CMT影响

摘要 目的：探讨视网膜激光光凝治疗视网膜静脉阻塞疗效及对眼内压（intraocular Pressure,IOP）、黄斑中心凹视网膜厚度（central Macular Thickness,CMT）影响。方法：选取2017年4月-2019年9月我院收治的80例视网膜静脉阻塞患者作为研究对象,随机将其分为两组,对照组40例,给予球旁注射曲安奈德注射液治疗;研究组40例,给予视网膜激光光凝治疗。观察两组患者临床疗效、治疗前后IOP、CMT以及最佳矫正视力（best Corrected Visual Acuity,BCVA）。结果：研究组总有效率显著高于对照组（97.50 % vs 77.50 %,P＜0.05）;治疗前,两组IOP、CMT、BCVA水平比较无差异（P>0.05）,治疗后研究组明显优于对照组（P<0.05）。结论：视网膜激光光凝治疗视网膜静脉阻塞疗效显著,能有效的改善患者IOP、CMT以及BCVA水平,具有一定的临床意义,值得临床推广和应用。     

Relationship of Spontaneous Retinal Vein Pulsation with Ocular Circulatory Cycle

Purpose

To determine the timing of spontaneous venous pulsation (SVP) relative to the ocular circulatory cycle by using the movie tool of confocal scanning laser ophthalmoloscope.

Methods

A video recording of the fundus was obtained using a confocal scanning laser ophthalmoscope (Spectralis HRA, Heidelberg Engineering, Heidelberg, Germany) at 8 frames/s in 47 eyes (15 glaucoma patients and 32 glaucoma suspects) with visible pulsation of both the central retinal artery (CRA) and vein (CRV). The timing of the maximum and minimum diameters of the CRA (CRA_max and CRA_min, respectively) and CRV (CRV_max and CRV_min, respectively) was identified during four pulse cycles. The interval between CRV_min and CRA_min, and between CRV_max and CRA_max was expressed as the number of frames and as a percentage of the ocular circulatory cycle.

Results

The ocular circulatory cycle (from one CRA_max to the next) lasted 7.7±1.0 frames (958.8±127.2 ms, mean±SD), with a mean pulse rate of 62.6 beats/min. The diameter of the CRA was increased for 2.4±0.5 frames (301.9±58.8 ms) and decreased for 5.3±0.9 frames (656.9±113.5 ms). CRV_max occurred 1.0±0.2 frames after CRA_max (equivalent to 13.0% of the ocular circulatory cycle), while CRV_min occurred 1.1±0.4 frames after CRA_min (equivalent to 14.6% of the ocular circulatory cycle).

Conclusions

During SVP, the diameter of the CRV began to decrease at early diastole, and the reduction persisted until early systole. This finding supports that CRV collapse occurs during ocular diastole.