BRVO CAN BE TREATED WITH INTRAVITREAL INECTIONS OF ANTI VEGF DRUGS AND GRID AND SECTORAL LASER .

1. BRVO
MANAGEMENT 2016
INTRAVITREAL INJ & LASER

2. DR DINESH MITTAL DR SONALEE MITTAL
DRISHTI EYE HOSP VIJAYNAGAR INDORE

3. BRVO
• Branch retinal vein occlusion (BRVO) is a common cause of
retinal vascular disease. The Beaver Dam Study estimated
the 15-year cumulative incidence of retinal vein occlusions
(RVO) at 2.3% in the population, with a majority of these
(78%) being BRVO. BRVO affects males and females
equally and occurs most frequently between the ages of 60
and 70. The pathologic interruption of venous flow in these
eyes almost always occurs at a retinal arteriovenous
intersection, where a retinal artery crosses over a retinal
vein. Systemic vascular diseases such as hypertension and
arteriosclerosis are risk factors for BRVO, probably
because they lead to thickening of the retinal artery.
•

4. PATHOGENESIS
• Because BRVO mostly occurs at arteriovenous
crossings, underlying arterial disease may play a
causative role. In 99% of 106 eyes with BRVO, the
artery was located anterior to the vein at the
obstructed site. Histopathologically, the retinal
artery and vein share a common adventitial sheath,
and in some cases, a common medium. The lumen
of vein may be compressed up to 33% at the
crossing site.

5. VISION loss from RVOs is
typically due to
• macular ischemia,
• macular edema,
• or complications from neovascular disease

6. CLINICAL FEATURES Symptoms
•Patients with BRVO present with sudden painless loss
of vision or a visual field defect. Subclinical
presentations may occur if a tributary distal to the
macula or a nasal retinal vein is involved. Rarely,
patients with BRVO will present with floaters from a
vitreous hemorrhage if the initial vein occlusion was
unrecognized and retinal neovascularization has
occurred.

7. CLINICAL FEATURES Signs
• Patients typically present with a wedge-shaped
distribution of intraretinal hemorrhage that is less
marked if the occlusion is perfused (or nonischemic),
and more extensive if the occlusion is nonperfused
(or ischemic) and associated with retinal capillary
nonperfusion. The Branch Vein Occlusion Study
Group defined ischemic BRVO as those with greater
than a total of five disc diameters of nonperfusion on
fluorescein angiography (FA).

8. CLINICAL FEATURES Signs
• The location of the venous blockage determines
distribution of intraretinal hemorrhage; if venous
obstruction is at the optic nerve head, two quadrants
of the fundus may be involved, whereas if the
occlusion is peripheral to the disc, one quadrant or
less may be involved with intraretinal hemorrhage.
The most common location for BRVOs is in the
superotemporal quadrant.

9. BRVO

14. BRVO
•Over time the intraretinal hemorrhage may completely
resorb. Without the characteristic segmental
distribution of intraretinal Hemorrhage, the
ophthalmoscopic diagnosis may be more difficult, but
the segmental distribution of retinal vascular
abnormalities that occurred during the acute phase will
persist and be apparent on FA. In many cases, macular
edema may also be detected by OCT .

15. BRVO
•Consequently, in chronic phase of disease, after
intraretinal hemorrhage absorption, diagnosis may
depend on detecting a segmental distribution of retinal
vascular abnormalities that may include capillary non
perfusion, dilation of capillaries, microaneurysms,
telangectatic vessels, and collateral vessel formation.
Nonocular signs such as systemic hypertension have
been associated with BRVOs. Thus, systemic blood
pressure may be elevated.

18. B/L BRVO
•In bilateral cases or cases involving young patients,
systemic manifestations of infectious disease,
inflammatory or autoimmune conditions, neoplasm,
or hypercoagulable states may be present.

19. Complications
• There are three common vision-limiting complications of BRVO:
• (1) macular edema;
• (2) macular ischemia; and
• (3) sequelae of neovascularization.
During the acute phase, extensive intraretinal hemorrhages may
obscure macular ischemia and macular leakage on FA. Under these
circumstances it is impossible to evaluate the perfusion status by FA
because the hemorrhage itself blocks the view of the vasculature. In
addition, the hemorrhage in the foveal center may reduce visual acuity
independently of any macular edema or ischemia.

20. Complications
• Since this reduction in visual acuity may recover completely if there
is no other cause for visual loss, such as macular edema or
macular capillary nonperfusion, observation in these cases can be
considered. When there is extensive foveal hemorrhage, OCT is an
important test to look for macular edema. Although it may be difficult
to provide a prognosis in acute phase, it is helpful to recognize that
about one-third to one-half of patients with BRVO have a return of
vision to 20/40 or better without any therapy.

21. Complications
• Retinal and iris neovascularization, vitreous hemorrhage,
traction retinal detachment, and neovascular glaucoma are
complications that manifest late in the course of the disease
due to ischemia. With the exception of macular ischemia, these
complications can largely be treated or prevented. Thus, it is
important that patients with BRVO be closely followed. From the
Branch Vein Occlusion Study, 31–41% of patients with ischemic
BRVO (defined as >5 disc diameters of nonperfusion on FA)
developed neovascularization or vitreous hemorrhage,
compared with 11% of patients with nonischemic BRVO.

22. CLINICAL EVALUATION
• A complete ophthalmic examination should be performed, paying
particular attention to history of glaucoma and signs of intraocular
inflammation, since these are risk factors for BRVO. Careful
examination of iris and angle should be performed in appropriate
cases to monitor for early signs of rubeosis or neovascular glaucoma.
Initially, when risk of macular edema and neovascularization is higher,
patients should be followed every month. Once stable, and if visually
significant macular edema and other complications are not present,
follow-up can be extended.

23. Fluorescein angiography
• To help verify the diagnosis and evaluate for complications, FA
should be obtained to delineate retinal vascular characteristics
that may have prognostic significance: macular leakage and
edema, macular ischemia, and large segments of capillary
nonperfusion that may portend eventual neovascularization. FA
will accurately define capillary abnormalities in BRVO . The
characteristic finding on FA is delayed filling of occluded retinal
vein. capillary nonperfusion, blockage from intraretinal
hemorrhages, microaneurysms , telangiectatic collateral
vessels, and dye extravasation from macular edema or retinal
neovascularization are other features encountered.

24. Fluorescein angiography
• In chronic cases, when hges have resolved, microvascular changes on
FA may provide the only clues of a previous BRVO. When FA
demonstrates macular leakage and edema with cystoid involvement of
the fovea, but no capillary nonperfusion, it is presumed that the macular
edema is the cause of vision loss. Under these circumstances, about
one-third of patients will spontaneously regain some vision. However,
patients who have had decreased vision for over 1 year as a result of
macular edema are much less likely to regain vision spontaneously

25. Fluorescein angiography
• . When macular edema is present ophthalmoscopically within
the first 6 months after a BRVO and there is little or no leakage
on FA, macular ischemia may be the cause of the macular
edema. In such circumstances, the edema almost always
spontaneously resorbs in the first year after the occlusion, often
with return of vision. Unfortunately, acute BRVOs with dense
intraretinal hges may make FA interpretation challenging due to
blockage of fluorescence by the hemorrhages. Thus, it is
advisable to obtain FA only after the intraretinal hemorrhages
have cleared significantly from the macula. Other diagnostic
tests, such as OCT, can be obtained in the acute phase to aid in
the diagnosis of macular edema.

26. Optical coherence tomography
• OCT has become the most important imaging modality in the
treatment of patients with BRVO and macular edema. OCT
offers a noninvasive and rapid method of quantitatively
measuring macular edema. OCT is frequently used to monitor
the response to treatment of macular edema and has been
used in place of FA in some treatment trials for BRVO. Unlike
FA, intraretinal hemorrhages have a minimal effect on the
interpretation of OCT, making this imaging modality helpful,
even in the acute setting with foveal hemorrhage.

27. OCT
• The characteristic findings of BRVO on OCT are cystoid edema,
intraretinal hyper reflectivity from hemorrhages, shadowing from edema
and hemorrhages, and occasionally subretinal fluid . In chronic cases,
photoreceptor inner-segment–outer-segment junction abnormalities from
long-standing macular ischemia and macular edema may also be seen .

28. BVO Study for neovascularization
•A separate group of patients in the BVOS were
randomized to receive PRP to prevent neovascular
complications. The BVOS demonstrated that
prophylactic PRP can lessen subsequent
neovascularization NV and, if NV already exists, that
PRP can lessen subsequent vitreous hemorrhage. Only
eyes with the type of BRVO that shows large areas (>5
disc diameters) of retinal capillary nonperfusion are at
risk for developing NV . About 40% of these eyes
develop NV , and of this 40%, about 60% will experience
periodic vitreous hemorrhage

29. BVO Study for neovascularization
•NVE OR NVD , or both, may develop at any time within
the first 3 years after an occlusion but are most likely to
appear within the first 6–12 months after the occlusion. If
PRP is applied in eyes with large areas of nonperfusion,
the incidence of NV can be reduced from about 40% to
20%. However, if one were to treat prophylactically, many
eyes (60%) that would never develop NV would receive
PRP . For this reason, it is recommended that PRP be
applied only after NV is observed.

30. Recommendations of
BVOS

31. summary recommendations
• The summary recommendations for management of acute branch vein
occlusion from BVOS emphasize waiting at least 3–6 months before
considering laser therapy. If the vision is reduced to 20/40 or worse,
wait 3–6 months for sufficient clearing of retinal hemorrhage to permit
high-quality FA and then evaluate for macular edema and macular
ischemia. If perfused macular edema accounts for visual loss, and
vision continues to be 20/40 or worse without spontaneous
improvement, consider grid macular photocoagulation.

32. For Macular edema, 6/12 or worse
• • Wait for clearance of retinal hemorrhages to
allow adequate fluorescence angiography
• • Determine if decreased visual acuity is caused
by macular edema (versus macular nonperfusion
– on FFA)

33. For Macular edema, 6/12 or worse
• If macular edema explains vision loss, and no
spontaneous improvement occurred by 3 months,
grid macular laser photocoagulation is
recommended
• • If capillary non perfusion explains decreased
visual acuity, laser treatment is not advised

34. For neovascularization
• • Good quality of FFA has to be obtained after
retinal hemorrhages have cleared sufficiently.
• • If more than five disc diameters of capillary
nonperfusion are present, the patient should be
followed at 4 month intervals to see development
of neovascularization

35. For neovascularization
• • If neovascularization develops, panretinal
photocoagulation to the involved sector should be
applied using green laser to achieve medium white
burns to cover entire involved segment
• Vitrectomy
• Indicated in complicated cases of Vitreous
hemorrhage, TRD and CRD.

36. summary recommendations
•However, this conclusion needs to be
balanced against the improvements in
vision seen with recent anti-vascular
endothelial growth factor (VEGF) agents. If
macular ischemia accounts for the visual
loss, no laser treatment is recommended to
improve vision.

37. SECTORAL
LASER

38. Retinal neovascularization
• NVI is a rare complication of BRVO. Retinal neovascularization is
particularly difficult to recognize in BRVO because the collaterals
that develop frequently may mimic NV . Arising from pre-existing
capillaries, these collaterals occur as vein-to-vein channels around
the blockage site, across the temporal raphe, and in other locations
to bypass the blocked retinal segment. These collaterals frequently
become quite tortuous, mimicking the appearance of NV if they are
evaluated by ophthalmoscopy alone. When it is unclear whether an
abnormal vascular pattern represents collateral formation or true
NV , the FA can be helpful because leakage from NV is more
prominent than from collateral vessels.

39. WHEN TO DO SECTORAL LASER
• The BVOS data strongly suggest that photocoagulation after the
development of NV is as effective in preventing vitreous
hemorrhage as is photocoagulation before the development of
neovascularization. When neovascularization is unequivocally
confirmed by FA, PRP can reduce the likelihood of vitreous
hemorrhage from about 60% to 30%. PRP can be applied with
argon blue green laser to achieve “medium” white burns (200–500
μm in diameter) spaced one burn width apart and covering the
entire area of capillary nonperfusion, as defined by FA, but
extending no closer than two disc diameters from the center of the
fovea and extending peripherally at least to the equator.

40. BRVO
BRVO WITH MACULAR ODEMA
INVOLVING CENTRE OF RETINA
NO
OBSERVATION
YES INTRAVITREAL
AVASTIN
FA
OBSERVATION FOR NVE ESP IF
CNP AREA MORE THAN 5 DD AREA
NO NVE
NVE PRESENT
VITREOUS HGE
SECTORAL LASER
GRID LASER
40 %

41. VITREOUS HAEMORRHAGE
• Of patients who develop neovascularization, 60% experience
episodes of vitreous hemorrhage if the condition is left untreated. In
some cases, the hemorrhage may be mild or may clear
spontaneously without causing permanent visual impairment.
However, in some patients, vitreous hemorrhage from
neovascularization can lead to prolonged visual disability in the
affected eye. When hemorrhage is dense, B-scan USG may help
rule out an associated TRD . Most eyes can be observed. If the
vitreous hemorrhage does not spontaneously clear in a few months,
a pars plana vitrectomy with sector endolaser photocoagulation
should be considered.

42. Steroid treatment
• Macular edema results from increased vascular permeability
mediated at least in part by an increase in VEGF.
Corticosteroids have been shown to inhibit the expression of
VEGF and therefore reduce macular edema in animal models.
The antiinflammatory effects of corticosteroids may further
potentiate its anti-VEGF effects and help attenuate macular
edema. Intraocular corticosteroids, however, have significant
side-effects, including cataract formation and glaucoma. IN
(SCORE) BRVO study, the effectiveness and safety of
intravitreal triamcinolone acetate (IVTA) for the treatment of
macular edema from BRVO were evaluated.

43. Steroid treatment
• Three-year results from 128 patients suggested that the laser
group maintained a significantly greater average increase in
vision (12.9 letters) compared with the two IVTA groups (4.4
letters, 1 mg and 8.0 letters, 4 mg). Significant side-effects from
IVTA included cataract formation and elevation of IOP requiring
treatment. Both side-effects were dose-dependent. As a result
of this study, IVTA is not recommended as first-line therapy for
macular edema in BRVO. However it can be considered in
patients where macular grid laser or other therapies are
ineffective, as treatment was found to be relatively safe,
especially in pseudophakic eyes.

44. GENEVA (dexamethasone implant)
study
• GENEVA (dexamethasone implant) study The Global Evaluation of
implantable dexamethasone in RVO with macular edema (GENEVA)
study evaluated a sustained-release, biodegradable, dexamethasone
intravitreal implant (Ozurdex, Allergan, Irvine, CA) for treatment of
macular edema in CRVO and BRVO patients. Ozurdex is a
biodegradable copolymer of poly (D,L-lactide-co-glycolide) acid
(PLGA) containing micronized dexamethasone. It is injected
intravitreally through a pars plana route using a 23-gauge custom
injector, and it gradually releases total dose of dexamethasone over
several months via Krebs cycle breakdown of the PLGA into lactic and
glycolic acid, and finally into water and carbon dioxide.

45. GENEVA (dexamethasone
implant) study
• A major difference between the GENEVA study and
other recent BRVO studies is the absence of a macular
grid laser group, or rescue laser treatment for the sham
group. The GENEVA study showed that the
dexamethasone implant is an alternative treatment to
macular grid laser in the appropriate patient population
(i.e., no glaucoma, pseudophakic) and is approved by
the Food and Drug Administration (FDA) for this
indication.

46. Anti-VEGF treatment
• Macular edema results from increased vascular permeability as a
response to retinal nonperfusion. In patients with BRVO,retinal ischemia
leads to the secretion of VEGF, which leads to increased vascular
permeability, vasodilation, migration of endothelial cells, and
neovascularization. Increased vascular permeability and perhaps
vasodilation lead to retinal edema. Thus, inhibition of VEGF is an
attractive treatment for macular edema from BRVO. There are several
anti-VEGF agents currently being investigated for use in treatment of
RVOs. We will discuss the use of ranibizumab (Lucentis), bevacizumab
(Avastin), and aflibercept (Eylea). Bevacizumab is a full-length,
humanized monoclonal antibody that binds all VEGF-A isoforms and is
FDA-approved for colorectal cancer, but is used off-label in the eye.

47. Anti-VEGF (Avastin/Lucentis)
• Intravitreal injection of anti - VEGF agents is the most
widely practiced mode of therapy during early stages of
BRVO these days.
• The edema disappears within 48-72 hours in most cases.
The disappearance of edema is so dramatic in most cases
that non-response raises doubt about efficacy of the vial
used! But the effect is short-lasting. Repeat injections are
needed at 2-4 month intervals to maintain whatever benefit
the patient gets after first injection.
• There is no difference among the two agents in terms of
efficacy.

50. Ranibizumab
• Ranibizumab is an affinity-purified, humanized monoclonal
antibody fragment (Fab) that binds all VEGF-A isoforms. The
BRAVO study showed that ranibizumab is superior to traditional
laser treatment for macular edema from BRVO with little risk of
adverse events. The current recommendation is therefore to
treat patients diagnosed with macular edema from BRVO with
monthly 0.5 mg ranibizumab. If treatment fails after 3 months
(<5 ETDRS letter gain, or improvement of <50 μm in central
subfield thickness), then traditional grid macular laser should be
performed.

51. Anti-VEGF
• The BRAVO study showed that PRN treatment did not adversely
affect the visual outcome after five scheduled monthly injections.
However, the timing of when to switch to PRN treatment was not
evaluated in the BRAVO study and thus the decision to switch to
PRN dosing should be based on factors such as improvement in
visual acuity, residual macular edema on OCT imaging, success of
prior injections, and expectations of the patient.

52. FOLLOW-UP
• The major complications that can lead to vision loss in patients
with BRVO include macular edema, macular ischemia, and
neovascularization. Treatment is available for macular edema
and neovascularization and follow-up should be tailored to
monitor the development of these complications adequately.
Initially, patients should be followed closely every month or 2
months for the development of macular edema and/or
neovascularization. Anti-VEGF therapy with or without macular
laser should be initiated for patients with macular edema
without spontaneous improvement

53. FOLLOW-UP
• Once macular edema has stabilized or has resolved, the follow-
up interval can be extended to 3–6 months or even longer for
stable chronic cases. Patients with previously untreated retinal
nonperfusion measuring >5 disc diameters should be followed
at closer intervals (3 months) due to increased risk for
neovascular complications. In patients where anti-VEGF
therapy and/or laser is not showing sufficient therapeutic
efficacy, steroids can be considered, particularly in
pseudophakic patients. Only after failure of medical therapy
should surgery be considered.

54. CONCLUSIONS
• BRVO is a common cause of vision loss, but many treatment options are
available and emerging therapies are under investigation. Current treatments
for macular edema include macular grid laser and intravitreal anti-VEGF
injections and intraocular corticosteroids. All have side-effects. Anti-VEGF
therapy typically lasts 4–6 weeks, necessitating frequent reinjections, and
corticosteroids can induce vision-limiting side-effects such as glaucoma and
cataract. However, due to its longer duration of action, corticosteroids may
play an important role in pseudophakic patients or in patients who do not
respond to laser and antiVEGF agents. Alternate delivery methods, including
topical,local depot injections, or perhaps even systemic delivery, will likely
emerge. Combination therapy with anti-VEGF agents acting to reduce
macular edema rapidly, and therapy aimed at restoring blood flow such as
vitrectomy with or without sheathotomy for BRVO may merit future
investigation to limit the need for chronic pharmacotherapy.

55. BRVO
BRVO WITH MACULAR ODEMA
INVOLVING CENTRE OF RETINA
NO
OBSERVATION
YES INTRAVITREAL
AVASTIN
FA
OBSERVATION FOR NVE ESP IF
CNP AREA MORE THAN 5 DD AREA
NO NVE
NVE PRESENT
VITREOUS HGE
SECTORAL LASER
GRID LASER
40 %

56. THANK
YOU
DR DINESH
DR SONALEE