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BRANCED RETINAL VEIN
OCCLUSION(BRVO)
Dr. Abhishek Onkar
Retinal Vein Occlusion
• Retinal vein occlusion is the second
most common cause of visual loss due
to retinal vascular disease1-3
• Types:
– Branch retinal vein occlusion (BRVO)
– Hemi-retinal vein occlusion (HRVO)
– Central retinal vein occlusion (CRVO)
• BRVO is the most common3
– Five-year incidence of 0.6% (21/3558) for
BRVO and
– 3x m/c than CRVO3
• Persistent macular edema causes VA
loss
1. Yau et al. Intern Med J. 2008; 2. RCO RVO guidelines. 2009; 3. Klein et al. Trans Am Ophthalmol Soc. 2000.
HRVOBRVO
2
EPIDEMIOLOGY
Definition : a segmental
intraretinal haemorrhage
not exceeding midline
caused by obstruction in
one of the branches of the
main vein draining the
corresponding retinal area
first
described by
Leber in 1877
Age
incidence :
more than
90% cases
>50yrs
No sex/race
predilection
usually
unilateral,
bilateral
only in 9%
3
CLASSIFICATION
• one of the
major branch
retinal veins is
occluded
Major
BRVO
• one of the
macular venules
is occluded
Macular
BRVO
4
66% : Superotemporal quadrant
THEORIES OF AETIO-PATHOGENESIS
1.Arterio-venous
Crossing
2.Degenerative Changes of
Vessel Wall
3.Hematological Disorders
4.Resistance to Activated
Protein C and Deficiency of
Protein C or Protein S
5.Deficiency of Antithrombin and
Mutation in the Prothrombin
Gene
6.Anti-Phospholipid Antibodies
and Hyperhomocysteinemia
5
Virchow’s triad
Hemo-
dynamic
changes
(venous
stasis)
Degenerative
changes of
vessel wall
Blood
hyper-
coaguability
6
Systemic risk factors associated with
retinal vein occlusion
Hypertension, hyperlipidemia, diabetes
mellitus
Atherosclerotic vascular disease: coronary
artery disease, high BMI, smoking
Neoplasia: polycythemia rubra vera,
multiple myeloma, leukemia
Vasculitis: systemic lupus erythematosus,
sarcoid, syphilis
Drugs: oral contraceptives, diuretics
Ocular risk factors include glaucoma and
hyperopia 7
Pathogenesis of Macular Edema in
BRVO
Vascular occlusion/hypoxia
Increased VEGF / IL-6 secretion
damage to the tight junctions of
capillary endothelial cells
BRB Breakdown
Fluid flux from vessels to tissue
according to Starling's law
8
BRVO : C/F
Major BRVO
• can be asymptomatic or
• with visual blurring usually
involving the sector of visual
field corresponding to the
area of the retina involved.
Macular BRVO
• there is always a central
visual disturbance with
normal peripheral vision
•asymptomatic/Sudden painless loss of Vn
•Vision loss at presentation is related to the extent of macular damage
from intraretinal oedema, haemorrhage or capillary non-perfusion
9
OPHTHALMOSCOPIC FEATURES
Acute RVO Chronic RVO
Intra-retinal haemorrhages : flame shaped
& dot - blot
Cystoid macular edema
Hard exudates RPE atrophy
Cotton wool spots ERM / sheathing of vessels
Optic disc edema Shunt vessels/ venous collaterals
Macular edema NVD/NVE/NVI
Dilated , tortuous retinal veins in
segmental distribution
Late complications :
VH
RD
NVG
10
Infero-temporal brvo in female aged 53years :
dilated , tortuous veins.
soft exudates and hemorrhages 11
Sheathed ST - VEIN 12
NV at macula 13
a sheathed supero temporal vein.
Haemorrhages and cotton wool
spots in supero-temporal acute
BRVO
14
The characteristic fluorescein
angiographic findings in BRVO include
ACUTEPHASE
• Delayed venous
filling/emptying
• Areas of Capillary
non-
perfusion/closure :
• A. Perfused
BRVO— <5DD
• B. Non-perfused
BRVO : >5DD
• Macular oedema :
perfused, non-
perfused or mixed
LATEPHASE
• micro vascular
abnormalities
• Late staining
and leakage
from the
affected veins is
seen
• particularly useful
in determining the
extent of ME and
Ischemia
• Blocked
fluorescence d/t
hemorrhages seen
through all phases
• Dilated capillaries,
microaneurysms
and telangiectatic
changes seen
15
Blocked fluorescence & non-perfusion
Late staining
Leakage around blocked vessel
late staining
16
NV and ME
17
OCT imaging
ME in IT-BRVO
L/E
18
SYSTEMIC W/U
19
W/U of patients with venous
obstruction (age>50 years)
Disorder Investigation
Hypertension B.P.
Diabetes F.B.S
CVA DUPLEX-U/S
ECG
Hyperlipidemia LIPID PROFILE
Temporal arteritis ESR
CRP
CBC
20
Algorithm for investigations in RVO
21
TREATMENT MODALITIES
T/T
MODALITIES
1. Anti-
aggregative
therapy and
firbrinolysis
2. Isovolemic
hemodilution
3.Sheathotomy
& vitrectomy
4. Intravitreal
& periocular
steroids
5.
Intravitreal
VEGF
inhibitors
6. Laser
therapy
22
• Current treatment options focus on the
sequelae of the occluded venous branch, such
as ME, NV, VH , TRD .
• The complex pathogenesis of this disease
requires investigation and treatment of all risk
factors (hypertension, diabetes mellitus, blood
lipid disorders, hematological disorders).
23
Intravitreal Corticosteroids
• In various studied doses from 4 to 25 mg,
triamcinolone acetonide (TA) has been
reported to be effective
• complications are raised intra-ocular pressure,
infectious endophthalmitis, post-injection
steroid-induced cataract, retinal detachment.
24
OZURDEX™
(dexamethasone intravitreal implant)
• OZURDEX® : FDA-approved t/t for macular edema
following BRVO.
• Injectable, biodegradable intravitreal implant contains 0.7 mg (700 μg)
dexamethasone in NOVADUR™ solid polymer DDS (preservative-free).
preloaded in sterile, single-use, applicator
• Poly (D,L-lactide-co-glycolide) PLGA biodegradable polymer matrix : slowly degrades to
lactic acid and glycolic acid as dexamethasone is gradually released. 25
ANTI-VEGF AGENTS : MOA
26
Humanized monoclonal IgG
antibody against VEGF-A
1.25 to 2.5 mg
monthly x 6 months
Off-label use
M/c a/e : conjunctival
hyperemia and subconjunctival
hemorrhage at injection site.
1.BEVACIZUMAB
(AVASTIN)
27
2.RANIBIZUMAB
( LUCENTIS )
Fab fragment of parent
molecule of bevacizumab
Designed for intra-ocular
use.FDA approved
0.5 or 0.3 mg
monthly x 6months
10-25 x more costly
28
Macular Grid Laser
Photocoagulation
MLG is recommended as an effective treatment to reduce the ME in BRVO :
after a period of 3 to 6 months after onset
and following absorption of the majority of hemorrhage
if VA is 20/40 or worse.
If FFA reveals macular nonperfusion, MLG not warranted.
Argon MLG is usually used for this purpose. However, diode laser (810 nm) and
krypton red laser (647 nm) also can be used.
29
Applied only to the area of leaking
capillaries
cover all areas of leaking
capillaries within 2 DD of
fovea
not extend beyond 2DD from
fovea
not extend within
the FAZ
avoid collateral vessels and
retinal haemorrhages
100 µm spots at 0.1 second
produce medium white burn
•spacing of one half to one burn-width apart
30
Scatter Laser
Photocoagulation
significantly reduced the development of retinal
neovascularization and vitreous hemorrhage.
if all eyes with large retinal nonperfusion were treated,
64% of these patients would never develop NV.
If only the eyes that develop NV were treated, the events
of VH decrease from 61% to 29%.
waiting is generally advocated until NV actually develops
before scatter photocoagulation is considered.
31
Laser spots spaced one
burn width apart
covering entire involved
segment
extending no closer than 2
DD from fovea
Spot Size : 200-500
microns
Duration : 0.1 s
Medium
white burn
Argon
green/
Ag
blue-
green 32
Clinical Trials and Venous
Occlusive Diseases
2010 Anti-VEGF Ranibizumab studies
BRAVO and CRUISE
2009 Steroid studies
SCORE Study Ozurdex Trials
Laser studies
1980s Branch Vein Occlusion Study
(BVOS)
1990s Central Vein Occlusion Study
(CVOS)
33
• Perform FA for macular edema, macular non-perfusion, retinal
neovascularization only after retinal hemorrhages have cleared
adequately (3-6 months)
• If macular edema is the cause of a vision less than 6/12,
undertake macular grid photocoagulation.
• If macular non-perfusion is the cause of decreased vision then no
laser treatment should be performed. Follow up these cases every
four months.
• If retinal non-perfusion more than 5 disc areas, follow up for
neovascularization at 4 monthly intervals.
• Undertake laser photocoagulation in the involved quadrant only if
neovascularization develops.
BVOS
34
BRVO Summary
BRVO:
• SCORE: Laser better than IVTA
• OZURDEX: Dexamethasone better
than sham (no laser arm)
• BRAVO: Ranibizumab monthly for 6
months better than observation/laser
in BRAVO. Improved VA: 61% vs 29%
eyes gained 15 or more letters
35
T/T summary in RVO’s
T/T Modality CRVO BRVO
Erythrocyte/platelet anti-
aggregative therapy
Routine use of ticlopidine / troxerutine for improving VA
or resolution of VH not recommended
Fibrinolysis Limited use in acute CRVO
(<11days): I.V. low dose rt-
PA +Heparin
Routine use not
recommended
Isovolemic hemodilution Routine use for improving VA or resolution of VH not
recommended
Pars plana vitrectomy Routine use not recommended
Intra-vitreal steroids Improve VA /resolve ME TA not sup. to MLG.
A/E >than MLG /anti-
VEGF
Intra-vitreal anti-VEGF Bevacizumab/ranimizumabused effectively for improving
VA , resolving ME & NV.Trials ongoing.
36
Modality CRVO BRVO
Grid laser
photocoagulation
Not recommended for t/t
of ME
Indicated in ME and
VA≤20/40 of 3 months
duration.
Not recommended in
macular ischemia .
Scatter laser
photocoagulation
For NV : prophylactic t/t
not recommended if
gonioscopy & dilated
fundus examination
possible every 4 weeks .
If NV +nt : prompt laser to
avoid sec. complications
Recommended if disc /
retinal NV +nt
37
Natural Course and Visual Prognosis
Determine the natural course of BRVO
efficiency of the
developing
collateral
circulation
integrity of arterial
perfusion to the affected
sector
Site/degree of
occlusion,
38
In general, BRVO has a good prognosis.
50–60% of eyes have a final VA of 20/40 or better even
without any treatment.
Chronic ME and VH d/t neovascularizations account most
frequently for a poor final VA.
Retinal neovascularization and persistent ME develop in
25% and 60% of eyes, respectively.
39

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BRVO

  • 2. Retinal Vein Occlusion • Retinal vein occlusion is the second most common cause of visual loss due to retinal vascular disease1-3 • Types: – Branch retinal vein occlusion (BRVO) – Hemi-retinal vein occlusion (HRVO) – Central retinal vein occlusion (CRVO) • BRVO is the most common3 – Five-year incidence of 0.6% (21/3558) for BRVO and – 3x m/c than CRVO3 • Persistent macular edema causes VA loss 1. Yau et al. Intern Med J. 2008; 2. RCO RVO guidelines. 2009; 3. Klein et al. Trans Am Ophthalmol Soc. 2000. HRVOBRVO 2
  • 3. EPIDEMIOLOGY Definition : a segmental intraretinal haemorrhage not exceeding midline caused by obstruction in one of the branches of the main vein draining the corresponding retinal area first described by Leber in 1877 Age incidence : more than 90% cases >50yrs No sex/race predilection usually unilateral, bilateral only in 9% 3
  • 4. CLASSIFICATION • one of the major branch retinal veins is occluded Major BRVO • one of the macular venules is occluded Macular BRVO 4 66% : Superotemporal quadrant
  • 5. THEORIES OF AETIO-PATHOGENESIS 1.Arterio-venous Crossing 2.Degenerative Changes of Vessel Wall 3.Hematological Disorders 4.Resistance to Activated Protein C and Deficiency of Protein C or Protein S 5.Deficiency of Antithrombin and Mutation in the Prothrombin Gene 6.Anti-Phospholipid Antibodies and Hyperhomocysteinemia 5
  • 7. Systemic risk factors associated with retinal vein occlusion Hypertension, hyperlipidemia, diabetes mellitus Atherosclerotic vascular disease: coronary artery disease, high BMI, smoking Neoplasia: polycythemia rubra vera, multiple myeloma, leukemia Vasculitis: systemic lupus erythematosus, sarcoid, syphilis Drugs: oral contraceptives, diuretics Ocular risk factors include glaucoma and hyperopia 7
  • 8. Pathogenesis of Macular Edema in BRVO Vascular occlusion/hypoxia Increased VEGF / IL-6 secretion damage to the tight junctions of capillary endothelial cells BRB Breakdown Fluid flux from vessels to tissue according to Starling's law 8
  • 9. BRVO : C/F Major BRVO • can be asymptomatic or • with visual blurring usually involving the sector of visual field corresponding to the area of the retina involved. Macular BRVO • there is always a central visual disturbance with normal peripheral vision •asymptomatic/Sudden painless loss of Vn •Vision loss at presentation is related to the extent of macular damage from intraretinal oedema, haemorrhage or capillary non-perfusion 9
  • 10. OPHTHALMOSCOPIC FEATURES Acute RVO Chronic RVO Intra-retinal haemorrhages : flame shaped & dot - blot Cystoid macular edema Hard exudates RPE atrophy Cotton wool spots ERM / sheathing of vessels Optic disc edema Shunt vessels/ venous collaterals Macular edema NVD/NVE/NVI Dilated , tortuous retinal veins in segmental distribution Late complications : VH RD NVG 10
  • 11. Infero-temporal brvo in female aged 53years : dilated , tortuous veins. soft exudates and hemorrhages 11
  • 12. Sheathed ST - VEIN 12
  • 14. a sheathed supero temporal vein. Haemorrhages and cotton wool spots in supero-temporal acute BRVO 14
  • 15. The characteristic fluorescein angiographic findings in BRVO include ACUTEPHASE • Delayed venous filling/emptying • Areas of Capillary non- perfusion/closure : • A. Perfused BRVO— <5DD • B. Non-perfused BRVO : >5DD • Macular oedema : perfused, non- perfused or mixed LATEPHASE • micro vascular abnormalities • Late staining and leakage from the affected veins is seen • particularly useful in determining the extent of ME and Ischemia • Blocked fluorescence d/t hemorrhages seen through all phases • Dilated capillaries, microaneurysms and telangiectatic changes seen 15
  • 16. Blocked fluorescence & non-perfusion Late staining Leakage around blocked vessel late staining 16
  • 18. OCT imaging ME in IT-BRVO L/E 18
  • 20. W/U of patients with venous obstruction (age>50 years) Disorder Investigation Hypertension B.P. Diabetes F.B.S CVA DUPLEX-U/S ECG Hyperlipidemia LIPID PROFILE Temporal arteritis ESR CRP CBC 20
  • 22. TREATMENT MODALITIES T/T MODALITIES 1. Anti- aggregative therapy and firbrinolysis 2. Isovolemic hemodilution 3.Sheathotomy & vitrectomy 4. Intravitreal & periocular steroids 5. Intravitreal VEGF inhibitors 6. Laser therapy 22
  • 23. • Current treatment options focus on the sequelae of the occluded venous branch, such as ME, NV, VH , TRD . • The complex pathogenesis of this disease requires investigation and treatment of all risk factors (hypertension, diabetes mellitus, blood lipid disorders, hematological disorders). 23
  • 24. Intravitreal Corticosteroids • In various studied doses from 4 to 25 mg, triamcinolone acetonide (TA) has been reported to be effective • complications are raised intra-ocular pressure, infectious endophthalmitis, post-injection steroid-induced cataract, retinal detachment. 24
  • 25. OZURDEX™ (dexamethasone intravitreal implant) • OZURDEX® : FDA-approved t/t for macular edema following BRVO. • Injectable, biodegradable intravitreal implant contains 0.7 mg (700 μg) dexamethasone in NOVADUR™ solid polymer DDS (preservative-free). preloaded in sterile, single-use, applicator • Poly (D,L-lactide-co-glycolide) PLGA biodegradable polymer matrix : slowly degrades to lactic acid and glycolic acid as dexamethasone is gradually released. 25
  • 27. Humanized monoclonal IgG antibody against VEGF-A 1.25 to 2.5 mg monthly x 6 months Off-label use M/c a/e : conjunctival hyperemia and subconjunctival hemorrhage at injection site. 1.BEVACIZUMAB (AVASTIN) 27
  • 28. 2.RANIBIZUMAB ( LUCENTIS ) Fab fragment of parent molecule of bevacizumab Designed for intra-ocular use.FDA approved 0.5 or 0.3 mg monthly x 6months 10-25 x more costly 28
  • 29. Macular Grid Laser Photocoagulation MLG is recommended as an effective treatment to reduce the ME in BRVO : after a period of 3 to 6 months after onset and following absorption of the majority of hemorrhage if VA is 20/40 or worse. If FFA reveals macular nonperfusion, MLG not warranted. Argon MLG is usually used for this purpose. However, diode laser (810 nm) and krypton red laser (647 nm) also can be used. 29
  • 30. Applied only to the area of leaking capillaries cover all areas of leaking capillaries within 2 DD of fovea not extend beyond 2DD from fovea not extend within the FAZ avoid collateral vessels and retinal haemorrhages 100 µm spots at 0.1 second produce medium white burn •spacing of one half to one burn-width apart 30
  • 31. Scatter Laser Photocoagulation significantly reduced the development of retinal neovascularization and vitreous hemorrhage. if all eyes with large retinal nonperfusion were treated, 64% of these patients would never develop NV. If only the eyes that develop NV were treated, the events of VH decrease from 61% to 29%. waiting is generally advocated until NV actually develops before scatter photocoagulation is considered. 31
  • 32. Laser spots spaced one burn width apart covering entire involved segment extending no closer than 2 DD from fovea Spot Size : 200-500 microns Duration : 0.1 s Medium white burn Argon green/ Ag blue- green 32
  • 33. Clinical Trials and Venous Occlusive Diseases 2010 Anti-VEGF Ranibizumab studies BRAVO and CRUISE 2009 Steroid studies SCORE Study Ozurdex Trials Laser studies 1980s Branch Vein Occlusion Study (BVOS) 1990s Central Vein Occlusion Study (CVOS) 33
  • 34. • Perform FA for macular edema, macular non-perfusion, retinal neovascularization only after retinal hemorrhages have cleared adequately (3-6 months) • If macular edema is the cause of a vision less than 6/12, undertake macular grid photocoagulation. • If macular non-perfusion is the cause of decreased vision then no laser treatment should be performed. Follow up these cases every four months. • If retinal non-perfusion more than 5 disc areas, follow up for neovascularization at 4 monthly intervals. • Undertake laser photocoagulation in the involved quadrant only if neovascularization develops. BVOS 34
  • 35. BRVO Summary BRVO: • SCORE: Laser better than IVTA • OZURDEX: Dexamethasone better than sham (no laser arm) • BRAVO: Ranibizumab monthly for 6 months better than observation/laser in BRAVO. Improved VA: 61% vs 29% eyes gained 15 or more letters 35
  • 36. T/T summary in RVO’s T/T Modality CRVO BRVO Erythrocyte/platelet anti- aggregative therapy Routine use of ticlopidine / troxerutine for improving VA or resolution of VH not recommended Fibrinolysis Limited use in acute CRVO (<11days): I.V. low dose rt- PA +Heparin Routine use not recommended Isovolemic hemodilution Routine use for improving VA or resolution of VH not recommended Pars plana vitrectomy Routine use not recommended Intra-vitreal steroids Improve VA /resolve ME TA not sup. to MLG. A/E >than MLG /anti- VEGF Intra-vitreal anti-VEGF Bevacizumab/ranimizumabused effectively for improving VA , resolving ME & NV.Trials ongoing. 36
  • 37. Modality CRVO BRVO Grid laser photocoagulation Not recommended for t/t of ME Indicated in ME and VA≤20/40 of 3 months duration. Not recommended in macular ischemia . Scatter laser photocoagulation For NV : prophylactic t/t not recommended if gonioscopy & dilated fundus examination possible every 4 weeks . If NV +nt : prompt laser to avoid sec. complications Recommended if disc / retinal NV +nt 37
  • 38. Natural Course and Visual Prognosis Determine the natural course of BRVO efficiency of the developing collateral circulation integrity of arterial perfusion to the affected sector Site/degree of occlusion, 38
  • 39. In general, BRVO has a good prognosis. 50–60% of eyes have a final VA of 20/40 or better even without any treatment. Chronic ME and VH d/t neovascularizations account most frequently for a poor final VA. Retinal neovascularization and persistent ME develop in 25% and 60% of eyes, respectively. 39