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.
HRVO
BRVO
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
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
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
ACUTE
PHASE
• 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
LATE
PHASE
• 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
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