- •Retinal Vein Occlusions
- •Preface
- •Acknowledgments
- •Contents
- •1.1 Anatomy and Histology
- •1.2 Microanatomy of the Retina
- •1.3 Vascular Anatomy
- •Bernoulli’s Principle and Deductions Concerning Changes in Central Retinal Vein Diameter at the Lamina Cribrosa
- •1.4 Pathologic Anatomy
- •1.4.1 Abnormalities of the Vessel Wall
- •1.4.2 Branch Retinal Vein Occlusion
- •1.4.3 Central Retinal Vein Occlusion
- •1.4.4 Hemicentral Retinal Vein Occlusion
- •1.5 Summary of Key Points
- •References
- •2.1 Abnormalities of the Blood
- •2.1.1 Thrombosis
- •2.1.2 Viscosity of Blood
- •2.2 Abnormalities of Blood Flow
- •2.2.1 Retinal Vascular Hemodynamics
- •2.2.1.1 Laplace’s Law
- •2.2.1.2 Poiseuille’s Law
- •A Misapplication of Poiseuille’s Law
- •2.2.1.3 Hemodynamics of Central Retinal Vein Occlusion
- •How Severe Must Central Venous Obstruction Be to Produce Symptoms?
- •The Central Retinal Artery in Central Retinal Vein Occlusion
- •2.2.1.4 Hemodynamics of BRVO
- •2.3 Macular Edema
- •2.3.1 Macular Anatomy and Its Relationship to Macular Edema in Retinal Vein Occlusion
- •2.3.2 Starling’s Law
- •2.3.3 The Retinal Pigment Epithelial Pump
- •2.3.4 Molecular Signaling in Macular Edema
- •Relevant Molecular Biologic Terminology
- •2.3.4.1 Vascular Endothelial Growth Factor
- •2.3.4.2 Other Retinal Cytokines with Lesser Roles
- •2.3.4.3 Molecular Signaling in BRVO
- •2.3.4.4 Molecular Signaling in CRVO
- •What Does the Response of RVO to Intravitreal Anti-VEGF Drugs Say About Pathophysiology?
- •2.4 Retinal Neovascularization
- •Spontaneous Venous Pulsations and CRVO
- •2.7 Animal Models of Retinal Vein Occlusion
- •2.7.1 Animal Models of BRVO
- •2.7.2 Animal Models of CRVO
- •2.8 Summary of Key Points
- •2.9 Future Directions
- •References
- •3.1 Background for Clinical Genetics
- •3.2 The Role of Polymorphisms in Genetic Studies
- •3.3 Types of Genetic Study Design
- •Why Are So Many Association Studies for Retinal Vein Occlusion Negative?
- •3.4 Studies of the Genetics of Retinal Vein Occlusion
- •3.4.1 Platelet Glycoprotein Receptor Genes
- •3.4.2.1 Pooled Retinal Vein Occlusion
- •3.4.2.2 Central Retinal Vein Occlusion
- •3.4.2.3 Branch Retinal Vein Occlusion
- •3.4.4 202210G > A Mutation of the Prothrombin Gene (Factor II Leiden)
- •3.4.6 Protein C
- •3.4.7 Protein S
- •3.4.8 Fibrinogen
- •3.4.9 Factor XII
- •3.4.12 Other Negative Genetic Association Studies
- •3.5 Summary of Key Points
- •References
- •4.1 Nosology of Retinal Vein Occlusions
- •4.2 Branch Retinal Vein Occlusion
- •4.3 Central Retinal Vein Occlusion
- •Central Retinal Vein Occlusion with Nonischemic and Ischemic Hemispheres
- •4.3.1 Conversion from Nonischemic to Ischemic Forms of Retinal Vein Occlusion
- •4.4 Summary of Key Points
- •References
- •Quantifying Risk
- •The Major Epidemiologic Studies of Retinal Vein Occlusion
- •5.2 Prevalence
- •5.2.1 Pooled Retinal Vein Occlusion
- •5.2.2 Branch Retinal Vein Occlusion
- •5.2.3 Central Retinal Vein Occlusion
- •5.2.4 Hemicentral Retinal Vein Occlusion
- •5.3 Incidence
- •5.3.1 Pooled Retinal Vein Occlusion
- •5.3.2 Branch Retinal Vein Occlusion
- •5.3.3 Central Retinal Vein Occlusion
- •5.4 Risk and Protective Factors for Retinal Vein Occlusion
- •5.4.1.1 Pooled Retinal Vein Occlusion
- •5.4.1.2 Branch Retinal Vein Occlusion
- •5.4.1.3 Central Retinal Vein Occlusion
- •5.4.1.4 Hemicentral Retinal Vein Occlusion
- •5.4.2 Gender
- •5.4.2.1 Pooled Retinal Vein Occlusion
- •5.4.2.2 Branch Retinal Vein Occlusion
- •5.4.2.3 CRVO
- •5.4.2.4 Hemicentral Retinal Vein Occlusions
- •5.4.3 Race
- •5.4.4 Laterality
- •5.4.5 Body Mass Index
- •5.4.6 Education
- •5.4.7 Physical Activity
- •5.4.8 Miscellaneous Factors Explored and Not Found Important
- •5.5.1 Pooled Retinal Vein Occlusion
- •5.5.2 Branch Retinal Vein Occlusion
- •5.5.3 Central Retinal Vein Occlusion
- •5.5.4 Hemicentral Retinal Vein Occlusion
- •5.6 Life Expectancy
- •5.7 Visual Impact of Retinal Vein Occlusions
- •5.8 Summary of Key Points
- •References
- •6.1 Introduction
- •6.2 Systemic Associations
- •6.2.1 Hypertension
- •6.2.1.1 Pooled Retinal Vein Occlusions
- •6.2.1.2 Branch Retinal Vein Occlusion
- •6.2.1.3 Central Retinal Vein Occlusion
- •6.2.2 Diabetes Mellitus
- •6.2.2.1 Pooled Retinal Vein Occlusion
- •6.2.2.2 Branch Retinal Vein Occlusion
- •6.2.2.3 Central Retinal Vein Occlusion
- •6.2.3 Hyperlipidemia
- •6.2.3.1 Pooled Retinal Vein Occlusions
- •6.2.3.2 Branch Retinal Vein Occlusion
- •6.2.3.3 Central Retinal Vein Occlusion
- •6.2.4 Cardiovascular Disease
- •6.2.4.1 Pooled Retinal Vein Occlusion
- •6.2.4.2 Branch Retinal Vein Occlusion
- •6.2.4.3 Central and Hemicentral Retinal Vein Occlusion
- •6.2.4.4 Stroke
- •6.2.4.5 Carotid Artery Disease and Peripheral Vascular Disease
- •6.2.5 Rheologic and Hematologic Abnormalities
- •6.2.6 Coagulation Abnormalities
- •6.2.6.1 Antiphospholipid Antibodies
- •6.2.6.2 Factor VII
- •6.2.6.3 Factor VIII
- •6.2.6.4 Lipoprotein a
- •6.2.6.5 Von Willebrand Factor
- •6.2.6.6 Other Coagulation Factors
- •6.2.7 Hyperhomocysteinemia
- •6.2.7.1 Pooled Retinal Vein Occlusion
- •6.2.7.2 Branch Retinal Vein Occlusion
- •6.2.7.3 Central and Hemicentral Retinal Vein Occlusion
- •6.2.8 Serum Folate
- •6.2.9 Serum B12
- •6.2.10 Smoking
- •6.2.11 Alcohol Consumption
- •6.2.14 No Underlying Vascular Risk Factor
- •6.3 Ocular Associations
- •6.3.1 Pooled Retinal Vein Occlusion
- •6.3.2 Branch Retinal Vein Occlusion
- •6.3.3 Central Retinal Vein Occlusion and Hemicentral Retinal Vein Occlusion
- •6.4 Practical Recommendations About the Systemic Workup of Patients with Retinal Vein Occlusion
- •History of the Standard Workup for Systemic Associations in Central Retinal Vein Occlusion
- •6.5 Retinal Vein Occlusion and Cardiovascular Disease Risk
- •6.6 Differences in Systemic Associations Between Ischemic and Nonischemic CRVOs
- •6.7 Summary of Key Points
- •References
- •7.1 Branch Retinal Vein Occlusion
- •7.1.1 Acute Phase
- •7.1.1.1 Symptoms
- •7.1.2 Clinical Signs
- •7.1.2.1 Visual Acuity
- •7.1.3 Chronic Phase
- •7.1.3.1 Clinical Signs
- •7.1.3.2 Visual Acuity
- •Why Does the Visual Outcome in Nonischemic, Macula-Involving Branch Retinal Vein Occlusions Usually Vary with the Size of the Involved Retina?
- •7.2 Central Retinal Vein Occlusion
- •7.2.1 Acute Phase
- •7.2.1.1 Symptoms
- •7.2.1.2 Clinical Signs
- •When Retinal Venous Congestion and Optic Disc Edema Are Not Central Retinal Vein Occlusion
- •What Is the Relationship of Central Retinal Artery Pressure and Cilioretinal Artery Pressure?
- •Retinal Whitening Does Not Equal Infarction
- •A Clinical Picture Predicted by a Hypothesis
- •7.2.1.3 Visual Acuity
- •7.2.2 Chronic Phase
- •Why Are Optic Disc Collaterals Associated with Worse Initial and Final Visual Acuity After CRVO?
- •7.2.2.1 Visual Acuity
- •7.3 Hemicentral Retinal Vein Occlusion
- •7.3.1 Clinical Signs
- •7.3.2 Visual Acuity
- •7.4 Summary of Key Points
- •References
- •Which Measure of Reproducibility Is Best?
- •8.1 Color Fundus Photography
- •8.2 Fluorescein Angiography
- •8.2.1 Branch Retinal Vein Occlusion
- •8.2.2 Central Retinal Vein Occlusion
- •8.3 Optical Coherence Tomography and the Retinal Thickness Analyzer
- •Methods of Analysis of OCT in RVO
- •8.4 Visual Field Testing
- •8.5 Electroretinography
- •Electroretinography Essentials for Retinal Vein Occlusions
- •8.5.1 Branch Retinal Vein Occlusion
- •8.5.2 Central Retinal Vein Occlusion
- •8.5.3 Hemicentral Retinal Vein Occlusion
- •8.6 Indocyanine Green Angiography
- •8.7 Color Doppler Ultrasonographic Imaging
- •8.8 Laser Doppler Flowmetry
- •8.9 Ophthalmodynamometry
- •8.10 Scanning Laser Doppler Flowmetry
- •8.11 Laser Interferometry to Measure Pulsatile Choroidal Blood Flow
- •8.12 Vitreous Fluorophotometry
- •8.13 Summary of Key Points
- •References
- •9.1 Terminology
- •9.2 Branch Retinal Vein Occlusion
- •9.3 Central Retinal Vein Occlusion
- •9.3.1 Clinical Characteristics
- •In the Face of Evidence that Fluorescein Angiography Is Poorly Predictive of Ischemia in Acute Central Retinal Vein Occlusion, Why Is It Widely Used?
- •9.3.2 Conversion from Nonischemic to Ischemic Central Retinal Vein Occlusion
- •9.3.3 Outcomes by Ischemic Status
- •9.4 Interaction of Ischemia with Effects of Treatments
- •9.4.1 Branch Retinal Vein Occlusion
- •9.4.2 Central Retinal Vein Occlusion
- •9.5 Summary of Key Points
- •References
- •10.1 Branch Retinal Vein Occlusion
- •10.2 Central Retinal Vein Occlusion
- •10.3 Hemicentral Retinal Vein Occlusion
- •10.4 Treatment of Posterior Segment Neovascularization in Retinal Vein Occlusion
- •10.5 Summary of Key Points
- •References
- •11.1 The Pathoanatomy and Pathophysiology of Iris and Angle Neovascularization
- •11.2 Clinical Picture of Anterior Segment Neovascularization
- •11.4 Anterior Segment Neovascularization in Branch Retinal Vein Occlusion
- •11.5 Anterior Segment Neovascularization in Central Retinal Vein Occlusion
- •The Problem of Undetected Anterior Segment Neovascularization After Central Retinal Vein Occlusion
- •Why Is Anterior Segment Neovascularization Less Common in Central Retinal Vein Occlusion Than in Central Retinal Artery Occlusion?
- •11.6 Anterior Segment Neovascularization in Hemicentral Retinal Vein Occlusion
- •11.7 Summary of Key Points
- •References
- •12.1 Branch Retinal Vein Occlusion with Macular Edema
- •12.2 Central Retinal Vein Occlusion with Macular Edema
- •12.3 Summary of Key Points
- •References
- •Visual Acuity Measurement in Treatment Studies
- •OCT Measurement of Macular Thickness in Treatment Studies
- •13.1 Medical Treatment of Retinal Vein Occlusion
- •13.1.1 Anticoagulation
- •13.1.2 Systemic Thrombolytic Therapy
- •13.1.3 Isovolumic Hemodilution
- •Recipe for Isovolumic Hemodilution
- •13.1.4 Plasmapheresis
- •13.2 Treatment of Previously Unsuspected Risk Factors for Retinal Vein Occlusion
- •13.3.1 Treatments for Macular Edema
- •Relative Corticosteroid Potencies
- •13.3.2 Treatments for Intraocular Neovascularization
- •13.4 Results of Clinical Studies of Treatments for Macular Edema Secondary to Retinal Vein Occlusions
- •13.4.1 Branch Retinal Vein Occlusion
- •13.4.1.1 Grid Laser
- •13.4.1.2 Subthreshold Grid Laser Treatment
- •13.4.1.3 Sector Panretinal Laser Photocoagulation
- •13.4.1.5 Posterior Subtenon’s Triamcinolone
- •13.4.1.6 Intravitreal Corticosteroids
- •13.4.1.7 Combination Treatments Involving Intravitreal Triamcinolone Injections
- •13.4.1.8 Arteriovenous Sheathotomy
- •13.4.1.9 Vitrectomy
- •13.4.1.10 Intravitreal Injection of Autologous Plasmin
- •13.4.2 Central Retinal Vein Occlusion
- •13.4.2.2 Combination Regimen: Bevacizumab, Panretinal Laser, and Grid Laser
- •13.4.2.3 Systemic Corticosteroids
- •13.4.2.4 Posterior Subtenon’s Triamcinolone Injection
- •13.4.2.5 Intravitreal Corticosteroids
- •13.4.2.6 Vitrectomy
- •13.5 Treatment of Intraocular Neovascularization
- •13.5.1 Sector Panretinal Laser Photocoagulation for Retinal and Disc Neovascularization After Branch Retinal Vein Occlusion
- •13.5.2 Vitrectomy for Intraocular Neovascularization with Vitreous Hemorrhage
- •13.5.3 Laser Panretinal Photocoagulation for Anterior Segment Neovascularization
- •13.6 Economic Considerations
- •13.7 Future Directions
- •13.8 Summary of Key Points
- •References
- •14.1 Pooled Retinal Vein Occlusions in the Young
- •14.2 Branch Retinal Vein Occlusion in Younger Patients
- •14.3 Central Retinal Vein Occlusion in Younger Patients
- •14.4 Workup in the Younger Patient with Retinal Vein Occlusion
- •14.5 Summary of Key Points
- •References
- •15.1 Failed and Unadopted Treatments for Branch Retinal Vein Occlusion
- •15.1.1 Sector Panretinal Laser Photocoagulation for Serous Retinal Detachment in Branch Retinal Vein Occlusion
- •15.1.2 Laser Chorioretinal Venous Anastomosis for Branch Retinal Vein Occlusion with Macular Edema
- •15.1.3 Intravenous Infusion of Tissue Plasminogen Activator
- •15.1.4 Intravitreal Injection of Tissue Plasminogen Activator
- •15.1.5 Macular Puncture for Branch Retinal Vein Occlusion with Macular Edema
- •15.2 Failed and Unadopted Treatments for Central Retinal Vein Occlusion
- •15.2.1 Grid Laser for Macular Edema in Central Retinal Vein Occlusion
- •15.2.2 Chorioretinal Venous Anastomosis for Nonischemic Central Retinal Vein Occlusion with Macular Edema
- •15.2.3 Radial Optic Neurotomy for Central Retinal Vein Occlusion
- •15.2.4 Retinal Endovascular Surgery with Intravenous Injection of Tissue Plasminogen Activator
- •15.2.5 Intravitreal Injection of Tissue Plasminogen Activator
- •15.2.6 Intravitreal Tissue Plasminogen Activator and Triamcinolone
- •15.2.7 Systemic Acetazolamide for Central Retinal Vein Occlusion with ME
- •15.2.8 Combined Central Retinal Vein Occlusion and Central Retinal Artery Occlusion
- •15.2.9 Optic Nerve Sheath Decompression
- •15.2.10 Section of the Posterior Scleral Ring
- •15.2.11 Infusion of High Molecular Weight Dextran
- •15.3 Failed and Unadopted Treatments for HCRVO
- •15.4 Summary of Key Points
- •References
- •16.1 Case 16.1: An Asymptomatic Central Retinal Vein Occlusion with Asymmetric Hemispheric Involvement
- •16.1.1 Discussion
- •16.2 Case 16.2: Chronic Macular Branch Vein Occlusion with Subtle Ophthalmoscopic Signs, More Obvious Fluorescein Angiographic Signs, and Macular Edema
- •16.2.1 Discussion
- •16.3 Case 16.3: Old Hemicentral Retinal Vein Occlusion with Late Vitreous Hemorrhage and Hyphema
- •16.3.1 Discussion
- •16.4 Case 16.4: Spontaneous Improvement of a Nonischemic Central Retinal Vein Occlusion
- •16.4.1 Discussion
- •16.5 Case 16.5: Conversion of a Nonischemic Hemicentral Retinal Vein Occlusion to an Ischemic One
- •16.5.1 Discussion
- •16.6 Case 16.6: Nonarteritic Ischemic Optic Neuropathy Following Branch Retinal Vein Occlusion
- •16.6.1 Discussion
- •16.7 Case 16.7: Differentiating Central Retinal Vein Occlusion from the Ischemic Ocular Syndrome
- •16.7.1 Discussion
- •16.8 Case 16.8: Late Development of Neovascularization Elsewhere After Ischemic Branch Retinal Vein Occlusion
- •16.8.1 Discussion
- •16.9 Case 16.9: Nonischemic Central Retinal Vein Occlusion with Secondary Branch Retinal Artery Occlusion
- •16.9.1 Discussion
- •16.10 Case 16.10: Nonischemic Central Retinal Vein Occlusion with Macular Edema or Asymmetric Diabetic Retinopathy with Diabetic Macular Edema?
- •16.10.1 Discussion
- •16.11 Summary of Key Points
- •References
- •Index
360 |
16 Case Studies in Retinal Vein Occlusion |
Table 16.1 Abbreviations used in case studies of retinal vein occlusions
Abbreviation
ASNV
BRVO
BVOS
CRV
CRVO
CSMT
CVOS
DD
ETDRS
FA
GL HCRVO IOS
IU
IVI
IVBI
IVTI logMAR
LCRVA
ME
MA
NAION
NVA
NVI
OCT
POAG
PSNV
PRP
RAPD
RON
RVO
SD-OCT
TPA
VA
VEGF
vein than for the inferior hemicentral vein.8 The more posterior the thrombus, the more channels for venous blood to exit to the choroidal venous outflow, reducing the venous backpressure as reflected in the greater venous dilation superiorly and the presence of the disc collaterals superiorly but not inferiorly. It is not possible to prove this interpretation, but it is consistent with the findings.
16.2Case 16.2: Chronic Macular Branch Vein Occlusion with Subtle Ophthalmoscopic Signs, More Obvious Fluorescein Angiographic Signs, and Macular Edema
An 81-year-old female who had lost her right eye to failed retinal detachment repair in 1954 saw her optometrist on 10/5/2010 with a complaint of blurred vision of the left eye of 3 months’ duration. At her examination in 2009, the best corrected VA of the left eye was 20/30, whereas it was now 20/50. The patient was noted by her optometrist to have one microaneurysm and was referred for a retinal consultation, which revealed ME on slit lamp biomicroscopy confirmed on SD-OCT (Fig. 16.3). A foveal cyst was present. Fluorescein angiography (FA) showed an intraretinal collateral vessel superior to the macula, but there was minimal late leakage of fluorescein (Fig. 15.4). How would you manage this case?
16.2.1 Discussion
When the hemorrhages of an acute macular BRVO resolve, the residual signs can be subtle, as in this case. Rare microaneurysms (MAs) may be seen. ME may be detected by OCT but not by clinical examination. It is common for there to be no leakage on FA yet to see ME on OCT (e.g., see Fig. 8.3).30
This case fulfills criteria that were used for entry into the Branch Vein Occlusion Study (BVOS).24 All intraretinal hemorrhage has cleared, the VA is 20/40 or worse, and at least 3 months have passed since the onset of the BRVO. An excellent quality FA was available that documented absence of macular ischemia. Based on the results of the BVOS, grid laser (GL) to the involved edematous retina would be rational. When this option was offered and compared to the alternative option of an intravitreal bevacizumab injection (IVBI), however, the patient elected the latter. Her reasoning was that the risk of a paracentral scotoma induced by GL was
16.2 Case 16.2: Chronic Macular Branch Vein Occlusion |
361 |
a |
b |
c |
d |
Fig. 16.1 Fundus images of the right eye of an 84-year-old woman with simultaneous, asymptomatic, nonischemic hemicentral retinal vein occlusions of the right eye. (a) Color fundus photograph of the right eye shows hemorrhages of all four quadrants of the fundus. The number of hemorrhages is higher in the superior hemisphere than the inferior hemisphere. On the superior disc margin, collateral vessels are present (the black arrow). The superior
veins (the green arrow) are more dilated than the inferior veins (the blue arrow). (b) Color fundus photograph of the fellow eye is notable only for the presence of macular drusen. (c) Spectral domain OCT (SD-OCT) image of the right macula. The scanning laser ophthalmoscopic fundus image on the left indicates the vertical orientation of the line scan at the right. The foveal depression is intact and there is no evidence of intraretinal edema
unattractive, something not incurred by IVBI. The 1 in 1,500 chance of endophthalmitis with IVBI did not seem to her to outweigh the reported benefits for VA in such cases. Although an adequately powered randomized controlled clinical trial comparing GL to IVBI has not been done, a small prospective randomized trial suggested that both OCT-measured macular thickness and VA improve more with IVBI than with GL.20
The patient’s ME and VA both improved with IVBI (the VA improved from 20/50 to 20/30), but
she was unable to tell the difference and elected not to have subsequent IVBIs. Follow-up 1 year later showed an unchanged examination and return of VA to 20/50. Mild ME does not inexorably lead to a progressive decline in VA in macular BRVO. In persistent diabetic ME, generally more severe than that manifested in this case, VA declines at an average rate of one Early Treatment Diabetic Retinopathy Study (ETDRS) letter per 72 days.4 An analogous study for BRVO with persistent ME has not been done.