Retinal Vein Occlusions Preferred Practice Pattern®

AMERICAN ACADEMY OF OPHTHALMOLOGY® Protecting Sight. Empowering Lives.® © 2019 by the American Academy of Ophthalmology Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2019.09.029 ISSN 0161-6420/19 Secretary for Quality of Care Timothy W. Olsen, MD Academy Staff Ali Al-Rajhi, PhD, MPH Andre Ambrus, MLIS Meghan Daly Flora C. Lum, MD Medical Editor: Susan Garratt Approved by: Board of Trustees September 7, 2019 © 2019 American Academy of Ophthalmology® All rights reserved AMERICAN ACADEMY OF OPHTHALMOLOGY and PREFERRED PRACTICE PATTERN are registered trademarks of the American Academy of Ophthalmology. All other trademarks are the property of their respective owners. Preferred Practice Pattern® guidelines are developed by the Academy's H. Dunbar Hoskins Jr., MD Center for Quality Eye Care without any external financial support. Authors and reviewers of the guidelines are volunteers and do not receive any financial compensation for their contributions to the documents. The guidelines are externally reviewed by experts and stakeholders before publication. Correspondence: Ali A. Al-Rajhi, PhD, MPH, American Academy of Ophthalmology, P. O. Box 7424, San Francisco, CA 94120-7424. E-mail: [email protected]. The Retina/Vitreous Preferred Practice Pattern® Panel members wrote the Retinal Vein Occlusions Preferred Practice Pattern® (PPP) guidelines. The PPP Panel members discussed and reviewed successive drafts of the document, meeting in person twice and conducting other review by e-mail discussion, to develop a consensus over the final version of the document. Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 Steven T. Bailey, MD, Retina Society Representative Jennifer I. Lim, MD Ron A. Adelman, MD, MPH, MBA, FACS Amani Fawzi, MD, Macula Society Representative Gurunadh A. Vemulakonda, MD, American Society of Retina Specialists Representative Gui-shang Ying, MD, PhD, Methodologist Christina J. Flaxel, MD, Chair We thank our partners, the Cochrane Eyes and Vision US Satellite ([email protected]), for identifying reliable systematic reviews that we cite and discuss in support of the PPP recommendations. The Preferred Practice Patterns Committee members reviewed and discussed the document during a meeting in June 2019. The document was edited in response to the discussion and comments. Preferred Practice Patterns Committee 2019 Robert S. Feder, MD, Chair Roy S. Chuck, MD, PhD Steven P. Dunn, MD Christina J. Flaxel, MD Steven J. Gedde, MD Francis S. Mah, MD Randall J. Olson, MD David K. Wallace, MD, MPH David C. Musch, PhD, MPH, Methodologist The Retinal Vein Occlusions PPP was then sent for review to additional internal and external groups and individuals in July 2019. All those returning comments were required to provide disclosure of relevant relationships with industry to have their comments considered (indicated with an asterisk below). Members of the Retina/Vitreous Preferred Practice Pattern Panel reviewed and discussed these comments and determined revisions to the document. In compliance with the Council of Medical Specialty Societies' Code for Interactions with Companies (available at www.cmss.org/codeforinteractions.aspx), relevant relationships with industry are listed. The Academy has Relationship with Industry Procedures to comply with the Code (available at http://one.aao.org/CE/PracticeGuidelines/PPP.aspx). A majority (88%) of the members of the Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 had no financial relationship to disclose. Retina/Vitreous Preferred Practice Pattern Panel 2018–2019 Christina J. Flaxel, MD: No financial relationships to disclose Ron A. Adelman, MD, MPH, MBA, FACS: No financial relationships to disclose Steven T. Bailey, MD: No financial relationships to disclose Amani Fawzi, MD: No financial relationships to disclose Jennifer I. Lim, MD: Genentech, Kodiak Sciences, EyePoint Pharmaceuticals—Consultant/Advisor; Genentech—Lecture Fees Gurunadh A. Vemulakonda, MD: No financial relationships to disclose Gui-shang Ying, MD, PhD: No financial relationships to disclose Preferred Practice Patterns Committee 2019 Robert S. Feder, MD, Chair: No financial relationships to disclose Roy S. Chuck, MD, PhD: Novartis, Shire—Consultant/Advisor Steven P. Dunn, MD: No financial relationships to disclose Christina J. Flaxel, MD: No financial relationships to disclose Steven J. Gedde, MD: No financial relationships to disclose Francis S. Mah, MD: Aerie Pharmaceuticals, Bausch + Lomb, EyePoint Pharmaceuticals, Novartis, Ocular Therapeutix, Shire, Sun Pharmaceuticals—Consultant/Advisor; Bausch + Lomb, Novartis, Shire, Sun Pharmaceuticals—Lecture Fees Randall J. Olson, MD: No financial relationships to disclose David K. Wallace, MD, MPH: No financial relationships to disclose David C. Musch, PhD, MPH, Methodologist: Chengdu Kanghong Biotechnology, IRIDEX, Notal Vision— Consultant/Advisor Secretary for Quality of Care Timothy W. Olsen, MD: No financial relationships to disclose Academy Staff Ali Al-Rajhi, PhD, MPH: No financial relationships to disclose Andre Ambrus, MLIS: No financial relationships to disclose Meghan Daly: No financial relationships to disclose Flora C. Lum, MD: No financial relationships to disclose The disclosures of relevant relationships to industry of other reviewers of the document from January to October 2019 are available online at www.aao.org/ppp.. OBJECTIVES OF PREFERRED PRACTICE PATTERN GUIDELINES P294METHODS AND KEY TO RATINGS P295HIGHLIGHTED FINDINGS AND RECOMMENDATIONS FOR CARE P296INTRODUCTION P297Disease Definition P297Patient Population P297Clinical Objectives P298BACKGROUND P298Prevalence and Incidence P298Risk Factors P298Natural History P299Rationale for Treatment P300CARE PROCESS P300Patient Outcome Criteria P301Diagnosis P301 History P301Examination P301Diagnostic Tests P302Management P304 Prevention and Early Detection P304Medical and Surgical Management P304Follow-up Evaluation P309Provider and Setting P309Counseling and Referral P309Socioeconomic Considerations P310APPENDIX 1. QUALITY OF OPHTHALMIC CARE CORE CRITERIA P311APPENDIX 2. INTERNATIONAL STATISTICAL CLASSIFICATION OF DISEASES AND RELATED HEALTH PROBLEMS (ICD) CODES P313LITERATURE SEARCHES FOR THIS PPP P314RELATED ACADEMY MATERIALS P314REFERENCES P315 Background: Retinal vein occlusion (RVO) occurs when there is partial or complete obstruction of a retinal vein, and it is classified by the location of the occlusion. An obstruction of the retinal vein at or posterior to the optic nerve head is a central retinal vein occlusion (CRVO), and complete or partial obstruction at a branch or tributary of the central retinal vein is a branch retinal vein occlusion (BRVO). Vision loss associated with a vein occlusion usually occurs from macular ischemia or edema, retinal hemorrhages, vitreous hemorrhage, and epiretinal membrane formation. Major risk factors for RVO includes older age (over 40 years of age), arteriosclerosis, systemic arterial hypertension, and diabetes. Specific risk factors associated with BRVO and CRVO are detailed in this Preferred Practice Pattern (PPP). The recommendations of this PPP are based on Cochrane-identified reliable systematic reviews. Rationale for treatment: Macular edema may complicate both CRVOs and BRVOs. The first line of treatment for associated macular edema is anti-vascular endothelial growth factors (anti-VEGFs). Intravitreal corticosteroids, with the associated risk of glaucoma and cataract formation, have demonstrated efficacy. Also, laser photocoagulation surgery in BRVO has a potential role in treatment. Patients who develop iris neovascularization or retinal neovascularization following a CRVO, peripheral panretinal photocoagulation (PRP) treatment is advised. Note, PRP may decrease progression of iris neovascularization and may prevent neovascular glaucoma. Anti- VEGF can be used in an adjunctive manner if angiogenesis continues after PRP. Care Process: Patient outcome criteria are to improve or stabilize visual function and vision-related quality of life, detection and treatment of neovascular complications and macular edema, and control of blood pressure, diabetes and blood glucose, and other risk factors through direct communication and coordination of care with the patient's primary care physician. Patients under evaluation for RVO should undergo thorough medical history, ocular exam, and appropriate retinal imaging as needed. Management recommendations are detailed in this PPP, which includes surgical management and follow-up evaluation. Due to the complexities of the diagnosis and treatment for RVO, the ophthalmologist should be familiar with the specific recommendations of relevant clinical trials. Ophthalmologists should involve primary care physicians of RVO patients as part of their management for systemic conditions. As a service to its members and the public, the American Academy of Ophthalmology has developed a series of Preferred Practice Pattern® guidelines that identify characteristics and components of quality eye care. Appendix 1 describes the core criteria of quality eye care. The Preferred Practice Pattern® guidelines are based on the best available scientific data as interpreted by panels of knowledgeable health professionals. In some instances, such as when results of carefully conducted clinical trials are available, the data are particularly persuasive and provide clear guidance. In other instances, the panels have to rely on their collective judgment and evaluation of available evidence. These documents provide guidance for the pattern of practice, not for the care of a particular individual. While they should generally meet the needs of most patients, they cannot possibly best meet the needs of all patients. Adherence to these PPPs will not ensure a successful outcome in every situation. These practice patterns should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the best results. It may be necessary to approach different patients' needs in different ways. The physician must make the ultimate judgment about the propriety of the care of a particular patient in light of all of the circumstances presented by that patient. The American Academy of Ophthalmology is available to assist members in resolving ethical dilemmas that arise in the course of ophthalmic practice. Preferred Practice Pattern® guidelines are not medical standards to be adhered to in all individual situations. The Academy specifically disclaims any and all liability for injury or other damages of any kind, from negligence or otherwise, for any and all claims that may arise out of the use of any recommendations or other information contained herein. References to certain drugs, instruments, and other products are made for illustrative purposes only and are not intended to constitute an endorsement of such. Such material may include information on applications that are not considered community standard, that reflect indications not included in approved US Food and Drug Administration (FDA) labeling, or that are approved for use only in restricted research settings. The FDA has stated that it is the responsibility of the physician to determine the FDA status of each drug or device he or she wishes to use, and to use them with appropriate patient consent in compliance with applicable law. Innovation in medicine is essential to ensure the future health of the American public, and the Academy encourages the development of new diagnostic and therapeutic methods that will improve eye care. It is essential to recognize that true medical excellence is achieved only when the patients' needs are the foremost consideration. All Preferred Practice Pattern® guidelines are reviewed by their parent panel annually or earlier if developments warrant and updated accordingly. To ensure that all PPPs are current, each is valid for 5 years from the approved by date unless superseded by a revision. Preferred Practice Pattern guidelines are funded by the Academy without commercial support. Authors and reviewers of PPPs are volunteers and do not receive any financial compensation for their contributions to the documents. The PPPs are externally reviewed by experts and stakeholders, including consumer representatives, before publication. The PPPs are developed in compliance with the Council of Medical Specialty Societies' Code for Interactions with Companies. The Academy has Relationship with Industry Procedures (available at www.aao.org/about-preferred-practice-patterns) to comply with the Code. Appendix 2 contains the International Statistical Classification of Diseases and Related Health Problems (ICD) codes for the disease entities that this PPP covers. The intended users of the Retinal Vein Occlusions PPP are ophthalmologists. Preferred Practice Pattern® guidelines should be clinically relevant and specific enough to provide useful information to practitioners. Where evidence exists to support a recommendation for care, the recommendation should be given an explicit rating that shows the strength of evidence. To accomplish these aims, methods from the Scottish Intercollegiate Guideline Network1McDonald HR Williams GA Scott IU Haller JA Maguire AM Marcus DM Laser scanning imaging for macular disease: a report by the American Academy of Ophthalmology.Ophthalmology. 2007; 114: 1221-1228Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar (SIGN) and the Grading of Recommendations Assessment, Development and Evaluation2Guyatt GH Oxman AD Vist GE et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google Scholar (GRADE) group are used. GRADE is a systematic approach to grading the strength of the total body of evidence that is available to support recommendations on a specific clinical management issue. Organizations that have adopted GRADE include SIGN, the World Health Organization, the Agency for Healthcare Research and Policy, and the American College of Physicians.3McMahon SK Haynes A Ratnam N et al.Increase in type 2 diabetes in children and adolescents in Western Australia.Med J Aust. 2004; 180: 459-461Crossref PubMed Google Scholar ♦All studies used to form a recommendation for care are graded for strength of evidence individually, and that grade is listed with the study citation.♦Tabled 1I++High-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of biasI+Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of biasI-Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of biasII++High-quality systematic reviews of case-control or cohort studiesHigh-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causalII+Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causalII-Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causalIIINonanalytic studies (e.g., case reports, case series) Open table in a new tab ♦Tabled 1Good qualityFurther research is very unlikely to change our confidence in the estimate of effectModerate qualityFurther research is likely to have an important impact on our confidence in the estimate of effect and may change the estimateInsufficient qualityFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Any estimate of effect is very uncertain Open table in a new tab ♦Tabled 1Strong recommendationUsed when the desirable effects of an intervention clearly outweigh the undesirable effects or clearly do notDiscretionary recommendationUsed when the trade-offs are less certain—either because of low-quality evidence or because evidence suggests that desirable and undesirable effects are closely balanced Open table in a new tab ♦The Highlighted Findings and Recommendations for Care section lists points determined by the PPP Panel to be of particular importance to vision and quality of life outcomes.♦All recommendations for care in this PPP were rated using the system described above. Ratings are embedded throughout the PPP main text in italics.♦Literature searches to update the PPP were undertaken in March 2018 and June 2019 in PubMed and the Cochrane Library. Complete details of the literature searches are available online at www.aao.org/ppp. The prognosis of retinal vein occlusions (RVOs) varies according to the site of the occlusion and the type of occlusion (ischemic or nonischemic). In general, more-distal RVOs with less occlusion have a better prognosis than more-proximal RVOs with greater ischemia. Central retinal vein occlusions (CRVOs) and hemi-CRVOs have clinically similar courses. They are associated with glaucoma and have a higher risk of anterior segment neovascularization and neovascular glaucoma. Branch retinal vein occlusions (BRVOs) and hemiretinal vein occlusions have a visible arterial-venous crossing where the occlusion occurs. Macular edema may complicate both CRVOs and BRVOs. The first line of treatment for associated macular edema is anti-vascular endothelial growth factors (anti-VEGFs). Intravitreal corticosteroids, with the associated risk of glaucoma and cataract formation, have demonstrated efficacy. Also, laser photocoagulation surgery in BRVO has a potential role in treatment. Optimizing control of systemic arterial hypertension, diabetes, serum lipid levels, and intraocular pressure (IOP) to control glaucoma are all important in the management of systemic risk factors, as is communicating end-organ damage to the primary care provider. Retinal vein occlusion (RVO) is the second most common retinal vascular disorder following diabetic retinopathy and is often associated with vision loss.4Buehl W Sacu S Schmidt-Erfurth U Retinal vein occlusions.Dev Ophthalmol. 2010; 46: 54-72Crossref PubMed Scopus (0) Google Scholar Retinal vein occlusion occurs when there is a partial or complete obstruction of a retinal vein, and it is classified by the location of the occlusion. An obstruction of the retinal vein at or posterior to the optic nerve head is referred to as a central retinal vein occlusion (CRVO), and a complete or partial obstruction at a branch or tributary of the central retinal vein is referred to as a branch retinal vein occlusion (BRVO). An RVO involves either a complete or partial decrease in venous outflow within the retinal circulation with varying degrees of retinal vascular leakage, leading to both macular edema and an increase of intravenous pressure that results in intraretinal hemorrhages.4Buehl W Sacu S Schmidt-Erfurth U Retinal vein occlusions.Dev Ophthalmol. 2010; 46: 54-72Crossref PubMed Scopus (0) Google Scholar Branch retinal vein occlusions typically occur at an arteriovenous crossing point, where there is a common adventitial sheath, and are more commonly detected in the superior temporal quadrant.5Weinberg D Dodwell DG Fern SA Anatomy of arteriovenous crossings in branch retinal vein occlusion.Am J Ophthalmol. 1990; 109: 298-302Abstract Full Text PDF PubMed Google Scholar The major risk factors for RVO include systemic arterial hypertension, arteriosclerosis, and diabetes.6Kumar B Yu DY Morgan WH Barry CJ Constable IJ McAllister IL The distribution of angioarchitectural changes within the vicinity of the arteriovenous crossing in branch retinal vein occlusion.Ophthalmology. 1998; 105: 424-427Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar A hemiretinal vein occlusion (HRVO) can present in different ways. An HRVO is an occlusion occurring at the disc that commonly involves half of the neurosensory retinal venous drainage, either the superior or inferior hemifield. This pattern occurs in 90% of HRVOs.7Sanborn GE Magargal LE Characteristics of the hemispheric retinal vein occlusion.Ophthalmology. 1984; 91: 1616-1626Abstract Full Text PDF PubMed Google Scholar Some HRVO patients may have two distinctive central retinal veins referred to as hemicentral retinal veins; one drains the superior and the other drains the inferior retinal hemisphere. Occlusion of one trunk is referred to as a hemi-CRVO.8Hayreh SS Hayreh MS Hemi-central retinal vein occulsion. Pathogenesis, clinical features, and natural history.Arch Ophthalmol. 1980; 98: 1600-1609Crossref PubMed Google Scholar In general, HRVOs are clinically similar to BRVOs and have a visible occlusion near a branch point. However, hemi-CRVOs are clinically similar to CRVOs—no crossing point is visible and there is increased risk of late-developing iris and angle neovascularization and secondary elevated intraocular pressures (IOPs). Differentiation between an HRVO and a hemi-CRVO is not always possible. The loss of vision that is associated with a vein occlusion usually occurs from macular ischemia or edema, retinal hemorrhages, vitreous hemorrhage, epiretinal membrane formation, rubeosis iridis, and neovascular glaucoma.4Buehl W Sacu S Schmidt-Erfurth U Retinal vein occlusions.Dev Ophthalmol. 2010; 46: 54-72Crossref PubMed Scopus (0) Google Scholar Other findings associated with RVOs include retinal arterial macroaneurysm formation and cilioretinal artery occlusions. It is now known that all vein occlusions are ischemic to varying degrees as the retina drained by the occluded vessels releases hypoxia related factors such as VEGF as described in the paper by Campochiaro et al, thus there is a spectrum of non-perfusion.9Mir TA Kherani S Hafiz G et al.Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion.Ophthalmology. 2016; 123 (e621.): 625-634Abstract Full Text Full Text PDF PubMed Google Scholar The patient population includes people over 40 years of age. The most common age range is from the 6th to the 7th decade.10Central Vein Occlusion Study GroupBaseline and early natural history report: the Central Vein Occlusion Study.Arch Ophthalmol. 1993; 111: 1087-1095Crossref PubMed Scopus (0) Google Scholar, 11Rogers S McIntosh RL Cheung N et al.International Eye Disease ConsortiumThe prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.Ophthalmology. 2010; 117: 313-319Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar Retinal vein occlusions are relatively uncommon in individuals under age 40. ♦Identify patients at risk for developing RVO♦Encourage management of potential risk factors for both CRVO and BRVO, including optimizing systemic blood pressure and diabetes as well as control of glaucoma and ocular hypertension♦Increase primary care awareness of the higher risk of cardiovascular and stroke complications in patients presenting with RVO♦Monitor for signs of posterior or anterior segment neovascularization and neovascular glaucoma following all RVOs, because nonischemic can become ischemic♦Treat patients who have vision loss or those at risk for vision loss after RVO♦Minimize treatment side effects that might adversely impact vision and/or vision-related quality of life♦Provide or refer the patient for visual rehabilitation services when permanent visual impairment results from the disease The prevalence of RVOs is about 0.5% in the 2008 general world population aged 30 years or older and is estimated to affect more than 16 million people worldwide.11Rogers S McIntosh RL Cheung N et al.International Eye Disease ConsortiumThe prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.Ophthalmology. 2010; 117: 313-319Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 12Jaulim A Ahmed B Khanam T Chatziralli IP Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications: an update of the literature.Retina. 2013; 33: 901-910Crossref PubMed Scopus (0) Google Scholar The prevalence appears to be similar in East Asia and in the United States. Branch retinal vein occlusions occur six to seven times more commonly than CRVOs.13Zhou JQ Xu L Wang S et al.The 10-year incidence and risk factors of retinal vein occlusion: the Beijing eye study.Ophthalmology. 2013; 120: 803-808Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar African Americans have an incidence of CRVO similar to white Americans, and a gender predilection does not seem to exist.11Rogers S McIntosh RL Cheung N et al.International Eye Disease ConsortiumThe prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.Ophthalmology. 2010; 117: 313-319Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar The prevalence of RVOs might be lower in East Indians (0.76/100), with a similar six-fold higher prevalence of BRVO compared with CRVO.14Jonas JB Nangia V Khare A Sinha A Lambat S Prevalence and associations of retinal vein occlusions: the Central India Eye and Medical Study.Retina. 2013; 33: 152-159Crossref PubMed Scopus (12) Google Scholar In a Japanese study, the 9-year incidence was 3% for any RVO, and there was a nine-fold higher rate of BRVO compared with CRVO.15Arakawa S Yasuda M Nagata M et al.Nine-year incidence and risk factors for retinal vein occlusion in a general Japanese population: the Hisayama Study.Invest Ophthalmol Vis Sci. 2011; 52: 5905-5909Crossref PubMed Scopus (29) Google Scholar The incidence rate is about 48/100,000 person-years in Korea.16Park SJ Choi NK Seo KH Park KH Woo SJ Nationwide incidence of clinically diagnosed central retinal artery occlusion in Korea, 2008 to 2011.Ophthalmology. 2014; 121: 1933-1938Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar In the United States, the 5-year incidence rate is 0.8 per 100, whereas the 15-year incidence is 2.3 per 100 for individuals 40 years of age or older at baseline.14Jonas JB Nangia V Khare A Sinha A Lambat S Prevalence and associations of retinal vein occlusions: the Central India Eye and Medical Study.Retina. 2013; 33: 152-159Crossref PubMed Scopus (12) Google Scholar, 16Park SJ Choi NK Seo KH Park KH Woo SJ Nationwide incidence of clinically diagnosed central retinal artery occlusion in Korea, 2008 to 2011.Ophthalmology. 2014; 121: 1933-1938Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar In China, the 10-year incidence rate for those 40 years of age or older at baseline is 1.9 per 100.13Zhou JQ Xu L Wang S et al.The 10-year incidence and risk factors of retinal vein occlusion: the Beijing eye study.Ophthalmology. 2013; 120: 803-808Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar In a pooled group of 68,751 subjects aged 30 to 101 years from 15 studies standardized to the 2008 world population, there were 5.2 per 1000 for any vein occlusions (CI = 4.4–6.0), 4.42 per 1000 for BRVO (CI = 3.7–5.2) and 0.8 per 1000 for CRVO (CI = 0.6–1.0).11Rogers S McIntosh RL Cheung N et al.International Eye Disease ConsortiumThe prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.Ophthalmology. 2010; 117: 313-319Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar The main risk factor for both CRVO and BRVO is older age. A prior RVO is a risk factor for an RVO in the fellow eye.12Jaulim A Ahmed B Khanam T Chatziralli IP Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications: an update of the literature.Retina. 2013; 33: 901-910Crossref PubMed Scopus (0) Google Scholar The chance of a person with a pre-existing CRVO developing a CRVO in the fellow eye is 1% per year.17Central Vein Occlusion Study GroupNatural history and clinical management of central retinal vein occlusion.Arch Ophthalmol. 1997; 115: 486-491Crossref PubMed Google Scholar Patients with a BRVO in one eye have a 10% risk of developing an RVO of either type in the fellow eye over 3 years.18Hayreh SS Zimmerman MB Podhajsky P Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics.Am J Ophthalmol. 1994; 117: 429-441Abstract Full Text PDF PubMed Google Scholar, 19Michels RG Gass JD The natural course of retinal branch vein obstruction.Trans Am Acad Ophthalmol Otolaryngol. 1974; 78: OP166-177PubMed Google Scholar The other major risk factors for BRVO differ from those for CRVO or hemi-CRVO. Risk of BRVO is more likely associated with local vascular factors (arterial-venous crossing changes) rather than local ocular factors. Risk factors for BRVO include systemic conditions such as arterial hypertension, hyperlipidemia, diabetes, and coronary artery disease.20Eye Disease Case-Control Study GroupRisk factors for central retinal vein occlusion.Arch Ophthalmol. 1996; 114: 545-554Crossref PubMed Google Scholar, 21Hayreh SS Zimmerman B McCarthy MJ Podhajsky P Systemic diseases associated with various types of retinal vein occlusion.Am J Ophthalmol. 2001; 131: 61-77Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar Controversy exists regarding the contribution of other hematologic factors, such as factor V Leiden and homocysteinemia, in the development of BRVO. These hematologic factors may be more likely to contribute to the development of CRVO, although there is not uniform agreement.