1. RETINAL VEIN OCCLUSION
Dr. Yousaf Jamal
FCPS Resident
Ophthalmology Unit
Hayatabad Medical Complex
01-01-11
Mar 16, 2013

2. Contents
• BRVO
– Demographics
– Pathogenesis
– Etiology
– Management
• Hx, examination, investigation
• Treatment
– Trials
– Guidelines
• HRVO
• Summary / Take Home Message
• MCQs
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3. Branch retinal vein occlusion (BRVO)
• First described by Leber a
• One of the branches of main vein are blocked
– Superotemporal branch…66% b
– Inferotemporal branch…22-43% b
– Nasal branches…0.5-2.6% c
– Macular branch…24% c
a Leber T. In: Graefe-saemisch. Verlag von Wilhelm Engelmann; 1877: 531.
b Lange GE et al. clinical & fluorescein angiography findings in patients with retinal vein occlusion. A unicenter study of 211
patients. Klin Monatsbl Augenheiked. 1992;201:234-9.
c Hayrey SS et al. ocular neovascularization with retinal vein occlusion III. Incidence of ocular neovascularization with retinal vein
occlusion. Opthalmology 1983;90:488.
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4. Demographics
• Three times more common than CRVO a
– Prevalence
• In united states…0.9% b
• In Australia > 48 yrs age…1.1% c
• In Singapore from 40-80 yrs age…0.6% d
• In china > 40 yrs age…1.3% e
a Cahill MT et al. Arteriovenous sheathotomy for branch retinal vein occlusion. Ophthalmol Clin North Am 2002;15:417–23.
b Klein R et al. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2000;98:133-41
c Mitchell P et al. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch
Ophthalmol 1996;114:1243–7.
d Lim L et al.Prevalence and risk factors of retinal vein occlusion in an Asian population.Br J Ophthalmol.Oct 2008;92(10):1316-9.
e Xu L et al. Retinal vein occlusions and mortality: the Beijing Eye Study. Am J Ophthalmol. Dec 2007;144(6):972-3.
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5. • Incidence
– 15-year cumulative incidence…1.8% *
• No racial or gender predilection
• Usual age…5th-6th decade
* Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye
Study. Arch ophthalmol. Apr 2008;126(4):513-8
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6. Pathogenesis
• Multifactorial
• Three mechanisms may be involved
– Compression of vein at arteriovenous (A/V)
crossing
– Degenerative changes of vessel wall
– Abnormal hematological factors
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7. Arteriovenous Crossing
• Koyanagi first described association btw A/V
crossing & BRVO
• Common adventitial sheath of retinal artery &
vein provides settings for occlusion
• Arteriosclerosis further aggravates the risk of
occlusion
Koyanagi Y. the role of arteriovenous crossing for occuring retinal branch vein occlusion. Klin Monatsbl Augenheikd.
1928;81:219-31.
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8. • Duker & brown a studied 26 BRVO pts…
– Found that artery crosses anterior to vein in all pts
• Zhao et al b studied 106 eyes with BRVO…
– They found artery anterior to vein in 99% cases
• However, in approx 60% of normal…artery
crosses anterior to vein without causing
BRVO
a Duker JS et al. anterior location of crossing artery in BRVO. Arch ophthalmol. 1989;107:998-1000.
b Zhao J et al. arteriovenous crossing patterns in BRVO. Ophthalmology. 1993;100:423-8.
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9. Degenerative changes of vessel wall
• Jefferies et al showed that…
– The expected venous compression at A/V
crossings doesn't exist… rather described…
– Bending of vein into nerve fiber layer at this point
without compression
• Histological findings of venous lumen at A/V
crossing in BRVO pts suggests thrombus
formation as to be a cause
Jefferies P et al. an anatomical study of retinal A/V crossings & their role in pathogenesis of BRVO. Aust N Z J Ophthalmol.
1993;21:213-7.
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10. • Seitz a described…
– No evidence of thrombus as to be the cause of
vein occlusion…rather he showed
– Alteration of venous endothelium & intima media
as root of pathogenesis of BRVO
• Frangeih et al b support Seitz hypothesis…
– 90% cases had evidence of intima media
hypertrophy
a Seitz R. the retinal vessels. Comparative ophthlmoscopic & histologic studies on healthy & diseased eyes. St. Luois, MO:
CVMosby; 1964:28
b Frangeih GT et al. histopathologic study of BRVO. Arch Ophthalmol. 1982;100:1132-40.
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11. Abnormal hematological factors
• Some suggest relation btw BRVO &
hyperviscosity of blood a
• Others suggest dysregulation of thrombosis-
fibrinolysis balance b
a Trope GE et al. Abnormal blood viscosity and haemostasis in longstanding retinal vein occlusion. Br J Ophthalmol. 1983;67:137–
42.
b Janssen MCH et al. Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis? Thromb Haemost.
2005;93:1021–6.
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12. Etiology
• Idiopathic…mostly • Inflammations
• Arteriosclerosis – Sarcoidosis
– HTN – Lyme disease
– Hyperlipidemia – Serpiginous
– Diabetes…least choroiditis
likely
• Open angle
glaucoma
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13. Hematological disorders
– Resistance to activated protein C
– Protein C or protein S deficiency
– Deficiency of Antithrombin III
– Genetic mutation in the prothrombin gene
– Anti-phospholipid antibodies
– Hyperhomocysteinemia
– Lupus erythematosus
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14. MANAGEMENT
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15. History
• Symptoms
– Asymptomatic…nasal BRVO
– Blurring of vision…painless & sudden
– Sector field defect
– Central defect…macular BRVO
• Past & Personal Hx
– Hyperlipidemia
– Hx of stroke, MI, TIA
– Hypercoagulable states
– Smoking & Alcohol
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16. • The Eye Disease Case-control Study Group
identified following risk factors *
– Systemic hypertension
– Cardiovascular disease
– An increased body mass index at 20 yrs age
– Glaucoma
– Higher serum levels of alpha 2-globulin
• DM is lacking evidence to be an independent
risk factor
* Risk factors for branch retinal vein occlusion. The Eye Disease Case-control Study Group. Am J Ophthalmol. Sep
15 1993;116(3):286-96
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17. Examination
– VA & BCVA
– Pupillary reactions
– Anterior segment neovessels…rare
– IOP
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18. • Fundus findings
– Acute BRVO
• Dilated tortuous vein distal to occlusion
• Flame shaped hemorrhages respecting horizontal raphe
• Retinal edema
• Macular hemorrhage…macular BRVO
• Fluid leakage from distal vein
• Occasionally…subhyaloid hemorrhage
• Rarely…vitreous hemorrhage
• Cotton-wool spots…ischemia
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22. – Chronic BRVO
• Loss of retinal transparency
• Collaterals around area of occlusion
• Arteriolar narrowing & sclerosis
• Vascular sheathing
• Hard exudates
• CME & pigment clumps at macula
• NVD or NVE…in 36% eyes with nonperfusion > 5 DD
• Retinal detachment…rare
– Exudative / Tractional / Rhegmatogenous
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25. Complications
• Macular complications
– Chronic macular edema
– Macular nonperfusion
– Epiretinal membranes
– Small foveal hemorrhages
– Hard exudates
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26. • Neovascularization & its sequel
– NVD & NVE
– Vitreous hemorrhage
– NVI & NVA
• Retinal detachments
– Rhegmatogenous
– Tractional
– Exudative
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27. Differential diagnosis
• Diabetic retinopathy
• Central Retinal Vein Occlusion
• Hypertensive retinopathy
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28. Ocular Investigations
• Fluorescein angiography
– Done with decreased vision despite hemorrhages
have cleared…usually 3 months
– In late stages…staining & leakage of dye from
vessel
– Macular edema & sensory detachment…dye
leakage & pooling
– Capillary non-perfusion…hypofluorescence
– Collaterals & new vessels can be differentiated
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30. • Optical coherence tomography (OCT )
– Measure retinal thickness quantitatively
– Useful in the follow-up of patients with macular
edema secondary to BRVO
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31. Systemic investigations
• The authors of the Branch Vein Occlusion
Study have recommended against extensive
testing in patients with typical BRVO *
• Certain laboratory studies may be useful in
atypical cases
– Bilateral cases
– In young pts
– In pts with a personal or family Hx of
thromboembolism
* Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. The
Branch Vein Occlusion Study Group. Am J Ophthalmol. Sep 15 1984;98(3):271-82
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32. – Prothrombin time & activated partial
thromboplastin time
– Protein C, protein S, factor V Leiden, and
Antithrombin III
– Homocystine
– Antinuclear antibody (ANA), lupus anticoagulant,
and Anticardiolipin
– Serum protein electrophoresis
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33. Natural history of BRVO
– ME resolves…41% cases by 7.5 months as
judged by OCT a
– VA generally improves with time b
• 6/12 or better…50-60%
• 6/60 or worst…25%
– Neovessels…36 % cases over unknown period c
a Rogers SL et al. Natural History of Branch Retinal Vein Occlusion: An Evidence-Based Systematic Review. Ophthalmology
2010;117:1094–1101
b Hayreh SS et al. Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics. Am J
Ophthalmol 1994;117:429–41.
c Branch Vein Occlusion Study Group Argon laser scatter photocoagulation for prevention of neovascularization and vitreous
hemorrhage in branch vein occlusion. A randomized clinical trial. Arch Ophthalmol 1986;104:34-41
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34. – Vitreous hemorrhage…41% eyes over unknown
period
– Bilateral BRVO…4.5-6.5% at presentation
– 10% pts develop BRVO in fellow eye over
unknown period
Rogers SL et al. Natural History of Branch Retinal Vein Occlusion: An Evidence-Based Systematic Review. Ophthalmology
2010;117:1094–1101
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35. Treatment
• Systemic treatment
– Medical treatment is not effective. Various
methods used…
• Anticoagulants
• Fibrinolytic agents
• Clofibrate capsules (atromid-s)
• Carbogen inhalation
• Hemodilution
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36. • Ocular treatment
– Pharmacotherapy
– Photocoagulation
– Surgical
• Certain clinical trials needs attention
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37. Branch Vein Occlusion Study (BVOS)
• Purpose
– To determine whether scatter argon laser
photocoagulation can prevent the development of
neovascularization.
– To determine whether peripheral scatter argon
laser photocoagulation can prevent vitreous
hemorrhage.
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38. – To determine whether macular argon laser
photocoagulation can improve visual acuity in
eyes with macular edema reducing vision to 20/40
or worse.
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39. • Description
– Approximately 500 patients were enrolled
– ½ were randomly assigned to treatment with argon
laser photocoagulation
– ½ remained untreated as controls
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40. • Results
– Argon laser treatment improves sight significantly
in patients who already have reduced vision due to
a complication of BVO called macular edema or
swelling
– In addition, laser will significantly reduce the
likelihood of vitreous hemorrhage.
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41. – The proven effective use of laser in treatment of
BVO was especially significant because the retina
cannot be replaced or transplanted if damaged by
the condition.
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42. SCORE-BRVO study
• Standard care vs. COrticosteroids for
REtinal vein occlusion study
• Funded by national eye institute in May 2003
• Multicentered RCT
• 411 participants
SCORE study Report # 6. Arch Ophathalmol. 2009;127:1101.
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53. • Another major study…BRAVO trial
• BRAVO: Anti-vascular endothelial growth
factor (VEGF) therapy vs. placebo in BRVO
Campochiaro PA. CRUISE. Retina congress 2009.
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64. The Royal College of Ophthalmologists
Guidelines
• Published in Feb. 2009.
• Macular edema
– FFA should be carried after 3 months if VA < 6/12
– Macular edema…grid pattern photocoagulation
– Macular ischemia…no benefit of photocoagulation
– Pts with VA < 6/60 & those with persistent
symptoms for > 01 year are unlikely to benefit
from photocoagulation
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65. – Periocular & intravitreal triamcinolone
• Both are effective but IVTA is better a
– Intravitreal bevacizumab b
• Effective in reducing ME
• Common regimen…2-3 inj over 5-6 months
– The role of posurdex c is still awaited
a Hayashi K et al. Intravitreal versus retrobulbar injections of triamcinolone for macular edema associated with branch retinal vein
occlusion. Am J Ophthalmol 2005;139(6):972-82.
b Russo V et al. Bevacizumab compared with macular laser grid photocoagulation for cystoid macular edema in branch retinal vein
occlusion. Retina 2009 Jan 23. [Epub ahead of print] PMID: 19174717.
c Clinicaltrials.gov Identifier NCT 00485836/00486018
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66. • Treatment of Neovascularization *
– Observation till neovessels develop
– NVD or NVE is an indication for sector
photocoagulation
– FFA is usually not necessary
* Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of neovascularization and hemorrhage
in branch vein occlusion. Arch Ophthalmol. 1986;104:34–41.
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67. Other treatments
• Laser-induced chorioretinal anastomosis
• Arteriolar constriction
• Arteriovenous Crossing Sheathotomy and
Vitrectomy
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68. • Follow-up
– Initial follow-up in all pts should be at 03 months
post occlusion
– Subsequent follow-up at 3-6 months…depends on
laser Tx & complications
– Follow-up after 2 yrs normally not required
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69. Hemicentral retinal vein occlusion
(HRVO)
• Synonyms
– Hemiretinal vein occlusions
– Hemisphere vein occlusion
• 1/2 - 2/3rd of retina may be involved
• Controversial position regarding part of
CRVO or BRVO
• Many authors suggest it as similar to CRVO *
* Appiah AP et al. differences in contributory factors among hemicentral, central and branch retinal vein occlusion. Ophthalmology
1989;96:364.
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72. • Classification
– Non-ischemic HRVO
– Ischemic HRVO
• Incidence of ocular Neovascularization in
I-HRVO…58% & NVG…3.2% *
• The risk of rubeosis in I-HRVO > BRVO but <
CRVO *
* Hayrey SS et al. ocular neovascularization with retinal vein occlusion III. Incidence of ocular neovascularization with retinal vein
occlusion. Ophthalmology 1983;90:488-506.
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73. • The risk of NVD appears greater for HRVO
than either I-CRVO or BRVO *
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74. The Royal College of Ophthalmologists
Guidelines
• The management of HRVO is similar to that
described for BRVO
• The guidelines for laser TX being those
described above for BRVO
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75. Summary
• BRVO is more common than CRVO
• Usually idiopathic but systemic or local cause
must be investigated in unusual cases
• Different trials make the Tx options more
difficult to be practiced so guidelines should
be kept in front
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77. Take home message
• Diagnosing RVO shouldn’t be a problem
• Awareness of recent trials is very crucial
• Role of physician
• Proper follow-up
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78. THANKS
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79. MCQs
1. A 68 yr old man presents for new onset DV. VA was
20/80 OD and 20/25 OS. Slit lamp biomicroscopy
revealed a quiet and clear anterior segment without
anterior neovascularization. Fundus examination
showed superotemporal quadrant of intraretinal
hemorrhages and cotton wool spots respecting the
horizontal raphe. There is ME with cystic spaces in
the fovea.
What diagnostic test would you order to evaluate this patient's
status?
1. Goldmann visual field and optical coherence tomography (OCT)
2. Intravenous fluorescein angiography (FA) and OCT
3. Electroretinogram and fundus autofluorescence
4. Indocyanine green angiography and OCT
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80. Ans. 2
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81. …Continued case 1…
• OCT foveal thickness analysis demonstrates
increased foveal thickness 450 µm OD. FA revealed
diffuse macular edema with retinal hemorrhage and
dilated tortuous retinal veins with a slow AV transit
time consistent with BRVO.
• If the treating physician opts to apply the BRAVO trial results to
this patient, what will treatment consist of?
1. Observation
2. Single grid macular laser treatment
3. Monthly intravitreal injections of an anti-VEGF agent
4. Monthly intravitreal injections of a corticosteroid
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82. Ans. 3
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83. …Continued case 1…
• How would treatment differ if the physician opts to
apply the SCORE-BRVO results?
1. Observation
2. Single grid macular laser treatment if the hemorrhage is not too
severe to perform
3. Monthly intravitreal injections of an anti-VEGF agent
4. Intravitreal injection of triamcinolone
Ans. 2
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84. …Continued case 1…
• The pt receives 6 monthly intravitreal inj of
ranibizumab. During this time, VA remains stable at
20/30 and OCT testing reveals decreased ME with
central retinal thickness of 289 µm. The physician
decides to observe the patient and by month 7, the
edema is back to 454 microns and vision has
decreased to 20/60.
• Which of the following options could be considered?
1. Observation
2. Grid macular laser treatment
3. Intravitreal injection of an anti-VEGF agent
4. Intravitreal injection of an anti-VEGF agent and grid macular
laser treatment
5. Any of the above
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85. Ans. 5
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86. …Continued case 1…
• If the same pt was to be offered BVOS protocol then
what would be the treatment option
1. Prophylactic macular grid laser
2. Prophylactic scatter laser
3. Observation
4. Laser treatment after 1 month
Ans. 3
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87. …Continued case 1…
• If the same pt had capillary nonperfusion of 5 DD &
no signs of neovascularization. Then what would be
the best option following BVOS protocol.
1. Immediate scatter laser
2. Scatter laser on next visit
3. Immediate PRP
4. Defer till neovessels develop
Ans. 4
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88. MCQ 2
• All of the following are major independent risk factors
for BRVO except
1. Hypertension
2. Diabetes mellitus
3. Cardiovascular disease
4. History of glaucoma
5. Increased BMI at 20 yrs of age
Ans. 2
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89. MCQ 3
• In BRVO, VA improves to > 6/12 with time without
any Tx in …
1. 35-45% cases
2. 45-50% cases
3. 50-60% cases
4. 60-70% cases
Ans… 3
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90. True / False
• The following are true regarding management of
BRVO
1. Laser Tx should be carried out within 3 months from the onset
of event to be effective
2. The clinical diagnosis is usually sufficient to decide on the
advantage of laser Tx in pt with ME
3. Pts with HTN are unlikely to benefit from laser Tx
4. If VA < 6/60, macular laser is unlikely to be beneficial
5. Laser Tx should be carried out in the presence of retinal non-
perfusion of > 5DD, based on FFA
Ans… F,F,F,T,F
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91. Next
• Lecture
• Dr. Shoaib (central serous retinopathy)
• Journal club
• Dr. Nazli
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