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Miscellaneous
BRVO – Current
Practice
G.V.N. Rama Kumar
MBBS, MD, DNB, FRCS
G.V.N. Rama Kumar MBBS, MD, DNB, FRCS
Greater Kailash Hospital, Old Palasia, INDORE, Madhya Pradesh, India
B
ranch retinal vein occlusion (BRVO) is a cause of low
vision among significant number of patients in this era
of patients with multiple metabolic and cardiovascular
ailments. Classical teaching mentions that it affects elderly
age group (>60 years) with no gender predominance.
However, more number of cases are being diagnosed at
younger ages because of changing life styles. In India,
inflammatory vein occlusions also contribute to significant
number of cases.
Multiple treatments have been described for BRVO. Among
them, anticoagulation therapy, areteriovenous sheathotomy,
laser chorio-retinal anastamosis, hemodilution and other
systemic therapies were not widely accepted as routine
treatment options.
disease. Occlusion can occur away from AV crossings in
cases of retinal vasculitis.
Involvement of superotemporal vein appears to be most
common as macula is affected and patients become
symptomatic early. Involvement of veins away from macula
gets diagnosed only during routine fundus examination
or, more commonly, after vision loss due to vitreous
hemorrhage.
In interim to late stages, compensated vein occlusion with
development of collateral circulation does not require any
active intervention except for regular follow-up.
After BVOS (Branch Vein Occlusion Study) published in
1984, there was no major advancement in its management
till recent years. Now, with the advent of anti – VEGF agents
and intra- or peri-ocular steroid therapy, it appears that the
BVOS lost its importance in last 2-3 years. Nonetheless, it is
still valid and remains so as it is the only well designed and
randomized clinical trial till date regarding management of
BRVO. Also, the untreated group of BVOS gave insight into
natural course of the disease.
This article aims to discuss current trends and acceptable
protocols of management of BRVO.
Etiopathology
Risk factors: Systemic Hypertension, Diabetes Mellitus,
Age more than 60 years, Glaucoma, Hemodynamic or
thromboembolic disease, Retinal Vasculitis of any cause.
Atherosclerosis and thrombus formation at arterio-venous
crossings of branch retinal vessels is the pathology
responsible for BRVO associated with systemic metabolic
Figure 1: Superotemporal BRVO
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Miscellaneous: BRVO – Current Practice
Figure 2: Interim stage of BRVO
Figure 4: Old BRVO with TRD involving macula
Horizontal field defect
Early symptom; along with low vision if macula also
involved
Floaters
Vitreous hemorrhage, inflammatory vein occlusion
Asymptomatic
Vein occlusion seen on routine clinical examination
Signs
Early
Moderate to severe vision loss, multiple dot and blot retinal
hemorrhages and cotton wool spots in the area of involved
vein with or without macular edema.
Figure 3: Compensated BRVO – disc collaterals
Uncompensated vein occlusion results in recurrent or
chronic macular edema and neovascularization and further
complications. Intraocular neovascularization supposedly
occurs with retinal capillary non perfusion area of more
than 5 disc diameters.
Symptoms
Sudden diminution of vision
BRVO involving macula: macular ischemia, macular
edema (CME), hemorrhage at fovea
BRVO away from macula: Vitreous hemorrhage (VH),
Tractional or combined tractional-rhegmatogenous retinal
detachment (TRD or CRD)
50 l DOS Times - Vol. 20, No. 9 March, 2015
Interim
Compensated vein occlusion: Vision >6/12, Sclerosed
retinal vein, Insignificant macular edema, Disc collaterals
Uncompensated vein occlusion: Vision <6/18,
macular edema, retinal neovascularization (NVE), Disc
neovascularization (NVD)
Late (uncompensated)
Severe vision loss (<6/60), chronic macular edema,
vitreous hemorrhage, TRD or CRD, iris neovascularization
(NVI), increased IOP
Systemic Investigations
All patients: Even in a known hypertensive or patient with
other known systemic risk factor, following investigations
Contact Lens
Figure 5: Before and 1 week after Avastin
are mandatory to know the “metabolic”status at the time of
development of BRVO.
BP Check, Hemogram (including peripheral blood
morphology), Blood sugar, Lipid profile, Basic coagulation
profile, ESR.
Selected patients: ANA, ANCA, RA factor, Chest X-ray,
Montoux test, Protein C, Protein S, Antithrombin III, Lupus
Anticoagulant, Homocysteine or any other investigation as
per the clinical suspicion.
Ocular investigations
OCT
Timing: It can be performed any time starting immediately
after the onset of symptoms. Asymptomatic patients with
good vision may not require OCT as the chances of macular
edema are less.
Figure 6: Recommended pattern of laser photocoagulation
after disappearance of retinal hemorrhages
It is a useful tool for monitoring treatment response and
also to diagnose recurrent edema.
Repeat testing: Whenever there is suspicion of intraocular
neovascularization.
Fundus flourescien angiography (FFA)
Treatment
First time: Better to be deferred till the time of near total
disappearance of retinal hemorrhages which usually takes
1-3 months.
Observation
Early: Good vision, No macular edema, Limited area of
involvement (macular BRVO)
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Miscellaneous: BRVO – Current Practice
Figure 7: Well compensated BRVO 6months after avastin
Late: Compensated BRVO
Anti-VEGF (Avastin/Lucentis)
Intravitreal injection of anti - VEGF agents is the most
widely practiced mode of therapy during early stages of
BRVO these days1.
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 injection2.
There is no difference among the two agents in terms of
efficacy.
Steroids
Topical, subtenon, intravitreal and oral routes of
administration have been described. Among them,
intravitreal and, to some extent, subtenon routes
are supppsed to be effective modalities. Intravitreal
triamcinolone acetonide was the first agent which was
found to be useful in resolving macular edema in cases of
vein occlusion.
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Figure 8: BRVO with NVD, NVE, vitreous
hemorrhage and traction on macula
Cases of inflammatory vein occlusions and pseudophakic
eyes benefit most from steroid therapy.
Intravitreal implants (Ozurdex) are supposed to give longest
resolution period for macular edema.
Issues of cataract formation/progression and IOP elevation
restrict the use of steroids as first line therapy in phakic eye
Contact Lens
•
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
These guidelines are still valid in late stages of disease as
the response to therapy is supposed to be permanent.
Vitrectomy
Indicated in complicated cases of Vitreous hemorrhage,
TRD and CRD.
Treatment of risk factors
Figure 9: Inflammatory BRVO with CME and NVE
responded to steroid therapy and photocoagulation
and steroid responders. Also, steroids have limited role in
retinal ischemia and preventing neovascularization3.
NSAIDs
Nepafenac or bromfenac are useful adjuncts to steroids or
anti VEGF agents to treat CME. They are not recommended
as monotherapy.
Retinal Laser
BVOS has well established the role of green laser in
treatment of BRVO. It has to be noted that the study was
published in pre-OCT and anti-VEGF era!
Recommendations of BVOS
For Macular edema, Visual acuity of 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)
• 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
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.
Strict metabolic control by timely referral to internist is of
utmost importance not only for efficient ocular treatment
but also to prevent further similar episodes in either eye
and also in other systems of body.
Debatable issues
Investigating for rare systemic diseases
In cases of BRVO in young patients with uncertain etiology,
these investigations are supposed to be advised to diagnose
rare coagulation or connective tissue disorders. These
include testing for protein C, protein S and antithrombin
III among others. Most of the times, they are expensive and
the results are equivocal and most of the internists don’t
have a clue about what needs to be done if an investigation
comes positive!
Observation vs treatment
Recent practice pattern by many clinicians includes use of
anti-VEGF in all cases as soon as the patient presents. The
point in favor of this practice is early inhibition of retinal
ischemia. But, it is preferred that in cases with no CME,
limited retinal involvement and good vision it is better to
observe than treat.
Timing of treatment
In cases having less vision and significant CME, how early
one should intervene is a matter of debate again. After the
advent of anti-VEGF, the recommendation of BVOS to wait
for 3 months is no more valid as accepted and practiced by
almost all of clinicians these days. Only issue is how early
to intervene?
Proponents of early intervention claim that early reversal
to normal structure helps restoring normal function and
inhibits after effects of ischemia. Others point out that, the
cases which may get compensated later on with formation
of collaterals also get treated without need if early therapy
is given. This issue is clearly debatable as there is no clear
evidence in support of either argument.
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Miscellaneous: BRVO – Current Practice
Anti VEGF vs Steroids vs Laser
As on today there is no direct comparative study to answer
this question. The protocol practiced by many is as follows:
1) Obtain OCT to diagnose / document CME
2) Anti-VEGF or intravitreal steroids to start with
3) Repeat injections if CME recurs before disappearance
of retinal hemorrhages
4) Obtain FFA after hemorrhages clear
5) Sectoral PRP laser or macular grid laser as described in
BVOS. Observe, if there is no NV or CME.
Number of sittings of therapy
Regarding intravitreal anti-VEGF, there are proponents
of PRN-based treatment as practiced in management of
CNVM. There is no well established protocol regarding
number of injections or treatment sittings required as many
cases show recurrent edema even after repeated injection
for more than 2 years. But, it is widely accepted that well
done sectoral PRP laser need not be repeated and results in
permanent cure in most cases.
Sectoral laser PRP for persistent or recurrent CME
BVOS has recommended macular grid laser only for
persistent CME. Sectoral PRP laser is recommended only
Sah Hospital
for cases of neovascularization. But, after the advent of antiVEGF and steroids as treatment modalities, short lasting
effect and the need for repeated injections has prompted
many clinicians to consider sectoral PRP as a permanent
cure even for cases of recurrent CME4,5.
As there are no randomized controlled trials with newer
treatments, these debatable issues remain unanswered
today.
References
1.
Loukianou E, Brouzas D, Chatzistefanou K, Koutsandrea C. Clinical,
anatomical, and electrophysiological assessments of the central
retina following intravitreal bevacizumab for macular edema
secondary to retinal vein occlusion. Int Ophthalmol. 2015 Mar 29.
[Epub ahead of print]
2. Ito Y, Saishin Y, Sawada O, Kakinoki M. Comparison of single
injection and three monthly injections of intravitreal bevacizumab
for macular edema associated with branch retinal vein occlusion.
Clin Ophthalmol. 2015;9:175-80.
3. Thom HH, Capkun G, Nixon RM, Ferreira A. Indirect comparisons
of ranibizumab and dexamethasone in macular oedema secondary
to retinal vein occlusion. BMC Med Res Methodol. 2014;12:140.
4. Parodi MB, Iacono P, Bandello F. Subthreshold grid laser versus
intravitreal bevacizumab as second-line therapy for macular edema
in branch retinal vein occlusion recurring after conventional grid
laser treatment. Graefes Arch Clin Exp Ophthalmol. 2014 Nov 11.
5. Yang CS, Liu JH, Chung YC, Chou YB, Hung KH. Combination
therapy with intravitreal bevacizumab and macular grid and scatter
laser photocoagulation in patients with macular edema secondary to
branch retinal vein occlusion. J Ocul Pharmacol Ther. 2015;3:17985.
(Most Advance Centre of
Eastern UP)
Hi-Tech I Care Centre
10, West Khushru Bagh Road, Allahabad Contact- 8400262225
Late Dr. A.P.Sah (1932 – 2012)
Founder–Sah Hospital & Varanasi Eye Bank Society
More than 33 Corneal Transplantation in 1960-65
(Experience in Cornea / Vitro Retinal Surgery)
•
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Short / Long Term Fellowship
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3. Phaco – 15 days to 3 months
Also available
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