2019年《EURETINA视网膜静脉阻塞诊疗指南》解读

视网膜静脉阻塞(retinal vein occlusion,RVO)是继糖尿病视网膜病变后常见的眼底血管性疾病。2011年发表的《视网膜静脉阻塞管理专家共识》对RVO的诊疗进行了全面的阐述。2019年8月,欧洲视网膜专家协会(European Society of Retina Specialists,EURETINA)则在2011年专家共识基础上更新了RVO诊疗指南,总结了大型临床试验结果,采纳更强证据等级的数据资料对RVO的诊疗进行了规范。2019年指南形式上采用了"基本原理-证据-推荐"的结构,对RVO进行全面总结。本文对该指南内容进行解读。     

Photocoagulation for retinal vein occlusion

The role of photocoagulation in retinal vein occlusion (RVO) has been studied since 1974. The most serious complications of central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) are: (i) visual deterioration, most commonly due to macular edema, and (ii) the development of ocular neovascularization (NV), particularly neovascular glaucoma (NVG), with hazardous consequences for vision and even the eye itself.Before discussing the role of photocoagulation in the management of NV and macular edema in RVO, it is crucial to gain a basic scientific understanding of the following relevant issues: classification of RVO, ocular NV in RVO, and the natural history of macular edema and visual outcome of RVO. These topics are discussed.In CRVO, ocular NV is a complication of ischemic CRVO but not of nonischemic CRVO. Photocoagulation has been advocated to prevent and/or treat the development of ocular NV and NVG. Since NVG is the most dreaded, intractable and blinding complication of ischemic CRVO, the role of photocoagulation and its management are discussed. Findings of three randomized, prospective clinical trials dealing with photocoagulation in ischemic CRVO are discussed.The role of photocoagulation in the management of ocular NV and macular edema in BRVO, and three randomized, prospective clinical trials dealing with those are discussed.Recent advent of intravitreal anti-VEGF and corticosteroid therapies has drastically changed the role of photocoagulation in the management of macular edema and NV in CRVO and BRVO. This is discussed in detail.     

Medical treatment of retinal vein occlusions

The medical treatment of retinal vein occlusion (RVO) is comprised of three main stages: identification and therapy of the detectable risk factors, specific treatment aimed at the occlusive form and treatment of RVO complications. Even though the possible medical management of RVO includes several treatments, the most interesting approaches have been: anticoagulant/antiaggregating agents, troxerutin, corticosteroid, fibrinolytic/thrombolytic agents, and hemodilution. Overall, the medical approach to RVO is still awkward and unsatisfactory. Randomized clinical trials are needed to assess the degree of efficacy of the medical treatment of the specific forms of RVO.     

Medical treatment of retinal vein occlusions

The medical treatment of retinal vein occlusion (RVO) is comprised of three main stages: identification and therapy of the detectable risk factors, specific treatment aimed at the occlusive form and treatment of RVO complications. Even though the possible medical management of RVO includes several treatments, the most interesting approaches have been: anticoagulant/antiaggregating agents, troxerutin, corticosteroid, fibrinolytic/thrombolytic agents, and hemodilution. Overall. the medical approach to RVO is still awkward and unsatisfactory. Randomized clinical trials are needed to assess the degree of efficacy of the medical treatment of the specific forms of RVO.     

从EURETINA最新指南看视网膜静脉阻塞诊疗策略的变化

视网膜静脉阻塞(retinal vein occlusion,RVO)是严重危及视功能的常见疾病,在临床治疗策略和方案上并未完全形成共识,国内至今也未见相关指南和共识发表,近期新的国际指南发布对RVO治疗方法和管理策略有了更为全面、清晰的推荐和建议,了解并解读相关指南可为临床实践提供参考,对规范和指导诊疗提供帮助。     

Retinal vein occlusion: current treatment

Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management.     

Ischemic retinal vein occlusion: characterizing the more severe spectrum of retinal vein occlusion

Retinal vein occlusion (RVO)-including central RVO, branch RVO, and hemicentral and hemispheric RVO—is the second most common vascular cause of visual loss, surpassed only by diabetic retinopathy. The presence and extent of retinal ischemia in RVO is associated with a worse prognosis. On this basis, most previously conducted studies considered ischemic retinal vein occlusion (iRVO) and non-iRVO as separate entities based on set thresholds of existing retinal ischemia as determined by fundus fluorescein angiography. Other diagnostic technologies have been used specifically in the differentiation of ischemic central retinal vein occlusion and nonischemic central retinal vein occlusion. To date, there is no fully accepted definition for iRVO. Some clinicians and researchers may favor establishing a clear differentiation between these forms of RVO; others may prefer not to consider iRVO as a separate entity. Whatever the case, retinal ischemia in RVO confers a higher risk of visual loss and neovascular complications; thus, it should be determined as accurately as possible in patients with this disease and be considered in clinical and experimental studies. Most recently conducted clinical trials evaluating new treatments for macular edema secondary to RVO included none or only few patients with iRVO based on previous definitions (i.e., few patients with sizeable areas of retinal ischemia were recruited in these trials), and thus it is unclear whether the results observed in recruited patients could be extrapolated to those with retinal ischemia. There has been scant research aiming at developing and/or testing treatments for retinal ischemia, as well as to prevent new vessel formation as a result of RVO. We provide a detailed review of the knowledge gathered over the years on iRVO, from controversies on its definition and diagnosis to the understanding of its epidemiology, risk factors and pathogenesis, the structural and functional effects of this disease in the eye and its complications, natural history, and outcomes after treatment. In each section, the definition of iRVO used is given so, independently of whether iRVO is considered a separate clinical entity or a more severe end of the spectrum of RVO, the information will be useful to clinicians to determine patient's risk, guide therapeutic decisions, and counsel patients and for researchers to design future studies.     

慎重审视激光诱导脉络膜视网膜静脉吻合术在视网膜静脉阻塞治疗中的作用

视网膜静脉阻塞(retinal vein occluSion，Rvo)是一种常见的致盲性眼病，目前尚无满意的治疗方法。近年研究发现，采用激光诱导脉络膜视网膜静脉吻合术(laser-induced chorioretinal venous anastomosis,LCRVA)治疗非缺血型RVO的初步结果令人满意，但也伴发一些并发症，有些可严重威胁视功能。LCRVA的激光参数和治疗技术还未标准化，适应证有待规范。在没有得到随机临床试验验证之前，必须权衡这一疗法的利弊，慎重使用。     

The burden of disease of retinal vein occlusion: review of the literature

Retinal vein occlusion (RVO) is the second most common cause of vision loss due to retinal vascular disease. A literature review was undertaken to understand the epidemiology, clinical consequence, current practice patterns, and cost of RVO. Pertinent articles were identified by computerized searches of the English language literature in MEDLINE supplemented with electronic and manual searches of society/association proceedings and bibliographies of electronically identified sources. Population-based studies report a prevalence rate of 0.5-2.0% for branch RVO and 0.1-0.2% for central RVO. The 15-year incidence rate is estimated to be 1.8% for branch RVO and 0.2% for central RVO. Patients with RVO report lower vision-related quality of life than those without ocular disease. Available treatment options are limited. Until recently there was no treatment for central RVO. Laser photocoagulation is only recommended for branch RVO in patients who have not experienced severe vision loss. Emerging evidence on the effectiveness of intravitreal anti-vascular endothelial growth factor therapy and dexamethasone intravitreal implant is promising. Information on the treatment patterns and cost of RVO is extremely limited with one retrospective analysis of secondary insurance payment data identified and limited to the United States population only. A better understanding of the economic and societal impact of RVO will help decision makers evaluate emerging medical interventions for this sight-threatening disease.     

Retinal vein occlusion and hyperhomocysteinemia

INTRODUCTION: Previous studies have reported that an elevated plasma homocysteine level is a risk factor for vascular disease. The aim of this study is to determine whether hyperhomocysteinemia is a risk factor for retinal vein occlusion (RVO) and whether it is a prognostic factor. PATIENTS AND METHODS: The plasma homocysteine level was measured in 101 patients and compared to the plasma homocysteine level of controls. The relation between plasma homocysteine level and the other known risk factors of retinal vein occlusion was studied, as well as the correlation between the clinical outcome of the RVO and the plasma homocysteine level. RESULTS: The mean plasma homocysteine level was significantly higher in the 101 RVO patients than in the 29 controls (11.9 mmol/l vs 8.6, p<0.001). We found no relation between plasma homocysteine and other risk factors of vascular disease except for the hematocrit level. Hyperhomocysteinemia was more frequent in the ischemic forms and in bilateral RVO, but the difference was not statistically significant. CONCLUSIONS: Hyperhomocysteinemia seems to be an independent risk factor for RVO and was more frequent in severe RVO, but our study did not evidence an association with a severe prognosis. Vitamin therapy can decrease homocysteinemia but its efficacy in the prevention and in the treatment of RVO remains to be demonstrated.     

Exudative retinal detachment subsequent to retinal vein occlusion.

Previous studies have shown the possible development of exudative retinal detachment (ERD) as a complication of retinal vein occlusion (RVO). Considering 473 consecutive cases of RVO, only 3 cases of ERD with peculiar clinical aspects were discovered. In the first case, the ERD followed a branch RVO, but it developed in the opposite quadrant, with a late occurrence of venous retinal collaterals. In the second case, the ERD developed after a central RVO, having a retinoschisis aspect, with the subsequent occurrence of optic disk collateral vessels. In the third case, the ERD was secondary to a hemicentral RVO and involved the entire macular area. The pathogenesis of the ERD subsequent to RVO is still debated. Our experience seems to indicate that the ERD pathogenesis is linked not only to an inability of the draining vascular system, but also to an impairment in the function of the retinal pigment epithelium.     

视网膜静脉阻塞

视网膜静脉阻塞是老年人常见的眼底血管病,有典型的眼底表现,诊断一般不难。但因其病因未能完全确定,治疗还缺乏有效措施。目前的治疗主要是针对视力下降,甚或破坏眼球的并发症,如黄斑水肿及新生血管。针对国内尤其边缘地区眼科医师对本病治疗还缺乏统一的认识,本文结合文献,尤其是参考具有循证医学价值的文献以及我们的临床经验,对本病的临床诊治方法作一介绍。     

糖尿病视网膜病变合并视网膜静脉阻塞的临床分析

目的: 分析糖尿病视网膜病变(DR)合并视网膜静脉阻塞(RVO)的眼底特征及荧光素眼底血管造影(FFA)的图像特征。方法: 回顾性分析118例129眼DR合并RVO患者的视力、眼底、荧光素眼底血管造影(FFA)的图像特征及相关临床资料。结果: DR合并RVO的患者118例中,双眼同时发病有11例22眼,其余皆为单眼,其中66眼表现为视网膜中央静脉阻塞(CRVO),占51.2%,58眼表现为颞上分支静脉阻塞,占45.0%,其它分支静脉阻塞有5眼,占3.9%。FFA表现为:静脉阻塞区视网膜有大量神经纤维层出血,相应黄斑区荧光渗漏,掩盖了此眼DR的改变,对侧眼均可见DR不同级别的改变。结论: 糖尿病视网膜病变合并视网膜静脉阻塞眼底表现复杂,应与单一的糖尿病视网膜病变和视网膜静脉阻塞甄别。     

Management of retinal vascular diseases: a patient-centric approach

Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases.     

Thrombophilic and systemic risk factors in patients with retinal vein occlusion

Over the past years there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, as retinal vein occlusions (RVO) have a strong pathogenic correlation with the presence of hypertension or arteriosclerosis and the average age of affected patients is usually within the sixth or seventh decade of life, thrombophilia screening of RVO patients poses a particularly difficult diagnostic challenge. It is clear that to use medical resources appropriately and improve the level of interdisciplinary patient care in RVO, subgroup analysis is required. Just recently, some studies have demonstrated the significant role of coagulation disorders in specific subgroups of RVO patients and have provided recommendations for clinical practice. These results indicate that thrombophilic risk factors are significantly more prevalent among patients equal or less than 45 years of age at the time of RVO or a previous thromboembolic event, among patients with a remarkable family history of thromboembolism prior to the age of 45 years, or among patients without cardiovascular risk factors. According to these data, thrombophilia screening should be considered in these selected subgroups.     

Sustained suppression of VEGF for treatment of retinal/choroidal vascular diseases

Neovascular age-related macular degeneration (NVAMD) is the most prevalent choroidal vascular disease, and diabetic retinopathy (DR) and retinal vein occlusion (RVO) are the most prevalent retinal vascular diseases. In each of these, hypoxia plays a central role by stabilizing hypoxia-inducible factor-1 which increases production of vascular endothelial growth factor (VEGF) and other hypoxia-regulated gene products. High VEGF causes excessive vascular permeability, neovascularization, and in DR and RVO, promotes closure of retinal vessels exacerbating hypoxia and creating a positive feedback loop. Hence once VEGF expression is elevated it tends to remain elevated and drives disease progression. While other hypoxia-regulated gene products also contribute to pathology in these disease processes, it is remarkable how much pathology is reversed by selective inhibition of VEGF. Clinical trials have demonstrated outstanding visual outcomes in patients with NVAMD, DR, or RVO from frequent intraocular injections of VEGF-neutralizing proteins, but for a variety of reasons injection frequency has been substantially less in clinical practice and visual outcomes are disappointing. Herein we discuss the rationale, preclinical, and early clinical results of new approaches that provide sustained suppression of VEGF. These approaches will revolutionize the management of these prevalent retinal/choroidal vascular diseases.     

Follow up by colour Doppler imaging of 102 patients with retinal vein occlusion over 1 year

BACKGROUND/AIM: Retinal vein occlusion (RVO) is one of the most frequent ocular vascular diseases and leads to severe vision impairment. Colour Doppler imaging (CDI) is the first method which allows distinct evaluation of arterial and venous velocities in RVO. CDI is valuable for diagnosis of RVO and shows the effects of isovolaemic haemodilution. Patients with RVO were monitored by CDI for 1 year in order to clarify venous and arterial involvement in the pathogenesis of this disease. METHODS: Patients with RVO were monitored prospectively for 1 year with clinical examinations, fluorescein angiography, and CDI every 3 months. 102 adults referred for RVO for less than 2 months were enrolled. Unaffected eyes were used as control. The maximum systolic and diastolic flow velocities and the resistance index (RI) were measured in the central retinal artery (CRA) and the maximum and minimum blood flow velocities in the central retinal vein (CRV). RESULTS: During the year of observation, branch retinal vein occlusion (BRVO), ischaemic central retinal vein occlusion (CRVO), and non-ischaemic CRVO had a distinct pattern of venous velocity changes. BRVO had a similar profile to that observed in controls. Venous velocities were continuously lower in central forms, with the lowest values in ischaemic occlusion. In contrast, a brief decrease in arterial diastolic velocity was observed in ischaemic CRVO at presentation, correlated with arteriovenous passage time on fluorescein angiography, but with rapid normalisation. CONCLUSIONS: CDI findings were correlated with the type of RVO at all times during follow up. CDI showed persistent impairment of central venous velocity in CRVO whereas there was a fast initial values recovery of the arterial velocity. These results using CDI show strong evidence of a primary venous mechanism in RVO.     

Retinal vein occlusion in Armenia.

PURPOSE: To determine the demographic characteristics, associated ophthalmic and systemic conditions of retinal vein occlusion (RVO) and associations of central retinal vein occlusion among Armenian patients. METHODS: A retrospective study of 460 patients aged 30 years and older with a clinical diagnosis of RVO who were seen in the five-year period between January 1, 1993, and December 31, 1997 at the Eye Hospital. RESULTS: Signs of central RVO were found in 297 eyes (64.5%), branch RVO in 163 eyes (35.5%). Among the 460 patients occlusion was hemispheric in 4 eyes (2.4%), hemicentral in 5 eyes (3%). CRVO was more common among the younger patients (odds ratio [OR] = 2.42, 95% confidence interval [CI]: 1.06-5.65). Hypercoagulability was noted in the majority of RVO cases. Glaucoma was an associated condition (12.6%). Systemic hypertension was the most frequent association. In CRVO a significant association was found with hypertension (OR = 1.89, 95% CI: 1.23-2.70). CONCLUSIONS: Our results suggest RVO is associated with glaucoma and hypertension. RVO was more closely associated with hypertension than BRVO. There were no differences in the distribution for the site of occlusion with regard to sex in patients with CRVO and BRVO. No seasonal pattern was found in the onset of any type of RVO. Hypercoagulability may be a contributing factor in the pathogenesis. The findings reinforce recommendations to carefully evaluate patients with RVO for open-angle glaucoma, and to diagnose and treat systemic hypertension.     

Antithrombotic effect of ticlopidine in an experimental model of retinal vein occlusion

PURPOSE: Ticlopidine inhibits adenosine diphosphate (ADP)-induced platelet aggregation and may be effective in patients with retinal vein occlusions (RVO). This study tests the efficacy of ticlopidine in an animal model of RVO. METHODS: Rose bengal-mediated argon laser photothrombosis of retinal veins was created in rabbits pretreated with oral ticlopidine, aspirin, or saline. The number of laser spots necessary to produce a partial or complete RVO was recorded and tabulated. RESULTS: Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial (P =.02), or a complete (P =.002) RVO as compared to the control group. Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial RVO (P =.02). Pretreatment with aspirin significantly increased the number of laser spots needed to produce a complete RVO (P =.002). CONCLUSION: Ticlopidine may be a useful antiplatelet agent for the treatment of patients with RVO. Patients treated with ticlopidine should be monitored for the possible development of hematologic disorders.