branch retinal vein occlsion (brvo)

Apr 11, 2023

RETINAL VEIN OCCLUSION

Dr. Yousaf JamalFCPS Resident

Ophthalmology UnitHayatabad Medical Complex

01-01-11

Apr 11, 2023Retinal Vein Occlusion

• BRVO– Demographics– Pathogenesis– Etiology– Management

• Hx, examination, investigation• Treatment

– Trials– Guidelines

• HRVO• Summary / Take Home Message• MCQs

Contents


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.


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.


• 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


Pathogenesis

• Multifactorial• Three mechanisms may be involved

– Compression of vein at arteriovenous (A/V) crossing

– Degenerative changes of vessel wall– Abnormal hematological factors


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.


• 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.


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.


• 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.


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.


Etiology

• Idiopathic…mostly

• Arteriosclerosis– HTN– Hyperlipidemia– Diabetes…least

likely

• Open angle glaucoma

• Inflammations– Sarcoidosis – Lyme disease – Serpiginous

choroiditis


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


MANAGEMENT


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


• 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


Examination

– VA & BCVA– Pupillary reactions– Anterior segment neovessels…rare– IOP


• 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


– 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


Complications

• Macular complications– Chronic macular edema– Macular nonperfusion– Epiretinal membranes– Small foveal hemorrhages– Hard exudates


• Neovascularization & its sequel– NVD & NVE– Vitreous hemorrhage– NVI & NVA

• Retinal detachments– Rhegmatogenous– Tractional– Exudative


Differential diagnosis

• Diabetic retinopathy• Central Retinal Vein Occlusion • Hypertensive retinopathy


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


• Optical coherence tomography (OCT )– Measure retinal thickness quantitatively – Useful in the follow-up of patients with

macular edema secondary to BRVO


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


– 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


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


– 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


Treatment

• Systemic treatment– Medical treatment is not effective. Various

methods used…• Anticoagulants• Fibrinolytic agents• Clofibrate capsules (atromid-s) • Carbogen inhalation• Hemodilution


• Ocular treatment– Pharmacotherapy– Photocoagulation– Surgical

• Certain clinical trials needs attention


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.


– To determine whether macular argon laser photocoagulation can improve visual acuity in eyes with macular edema reducing vision to 20/40 or worse.


• Description– Approximately 500 patients were enrolled– ½ were randomly assigned to treatment

with argon laser photocoagulation– ½ remained untreated as controls


• 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.


– 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.


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.


• Another major study…BRAVO trial• BRAVO: Anti-vascular endothelial growth

factor (VEGF) therapy vs. placebo in BRVO

Campochiaro PA. CRUISE. Retina congress 2009.


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


– 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


• 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.


Other treatments

• Laser-induced chorioretinal anastomosis• Arteriolar constriction• Arteriovenous Crossing Sheathotomy

and Vitrectomy


• 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


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.


• 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.


• The risk of NVD appears greater for HRVO than either I-CRVO or BRVO *

* Hayreh SS et al. Hemi-central retinal vein occlusion. Pathogenesis, clinical features and natural history. Arch Ophthalmol 1980; 98:1600-9.


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


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


Take home message

• Diagnosing RVO shouldn’t be a problem• Awareness of recent trials is very crucial• Role of physician• Proper follow-up


THANKS

Apr 11, 2023Retinal Vein Occlusion Apr 11, 2023Retinal Vein OcclusionPage 79

MCQs1. 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 OCT3. Electroretinogram and fundus autofluorescence4. Indocyanine green angiography and OCT


Ans. 2


…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. Observation2. Single grid macular laser treatment3. Monthly intravitreal injections of an anti-VEGF agent4. Monthly intravitreal injections of a corticosteroid


Ans. 3



• How would treatment differ if the physician opts to apply the SCORE-BRVO results?

1. Observation2. Single grid macular laser treatment if the hemorrhage is

not too severe to perform3. Monthly intravitreal injections of an anti-VEGF agent4. Intravitreal injection of triamcinolone

Ans. 2


…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. Observation2. Grid macular laser treatment3. Intravitreal injection of an anti-VEGF agent4. Intravitreal injection of an anti-VEGF agent and grid macular laser

treatment5. Any of the above


Ans. 5



• If the same pt was to be offered BVOS protocol then what would be the treatment option

1. Prophylactic macular grid laser2. Prophylactic scatter laser3. Observation4. Laser treatment after 1 month

Ans. 3



• 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 laser2. Scatter laser on next visit3. Immediate PRP4. Defer till neovessels develop

Ans. 4


MCQ 2

• All of the following are major independent risk factors for BRVO except

1. Hypertension2. Diabetes mellitus3. Cardiovascular disease4. History of glaucoma5. Increased BMI at 20 yrs of age

Ans. 2


MCQ 3

• In BRVO, VA improves to > 6/12 with time without any Tx in …

1. 35-45% cases2. 45-50% cases3. 50-60% cases4. 60-70% cases

Ans… 3


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 Tx4. If VA < 6/60, macular laser is unlikely to be beneficial5. 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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• Lecture• Dr. Shoaib (central serous retinopathy)

• Journal club• Dr. Nazli

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