The Medical Practice of Ray M. Balyeat, MD: Limited to Medical & Surgical Management
of Diseases of the Macula, Retina & Vitreous
Retinal Vascular Disease

Branch Retinal Vein Occlusion
What is a Branch Retinal Vein Occlusion?
Despite similarities between central retinal vein occlusion (CRVO) and branch retinal
vein occlusion (BRVO), the natural history for each entity differs. Therefore
treatments and results vary from one condition to the other.   Hemiretinal
(parapapillary) vein occlusions involving the superior or inferior half of the retina are
functionally variants of CRVO and should not be thought similar to BRVO.

Retinal vascular damage may occur from longstanding hypertension.  In some eyes
microscopic blood clot formation (thrombus formation) may secondarily occur.  In
the retina small arteries (arterioles) and small veins (venules) share a common
“covering” (adventitial sheath).  Where a retinal arteriole crosses over a venule the
potential for constriction of the weaker walled venule exists setting the stage for a
point of increased turbulence of blood flow that increases the risk of thrombus
formation.  If a thrombus forms, blood flow through the venule may be compromised
or cease altogether.  Most BRVOs affect the upper/outer portion (superotemporal
quadrant) of the retina thus leading to the sensation of blurry or missing vision just
below the central visual axis (retinal and visual fields are inversely related).  If retinal
blood vessel damage from BRVO extends into the central retina, the macula, central
or “reading” vision loss may occur.  



If sufficient damage to the capillaries (the tiniest blood vessels of the human body
through which oxygen is delivered to target tissues) has occurred during the
development of a BRVO, retinal swelling (retinal edema) may develop.  During the
early stages of BRVO, retinal edema is accompanied by retinal hemorrhages and
small white patches of blood-deprived retinal tissue (cotton-wool spots).  Edema,
hemorrhages and cotton-wool patches are classically seen in the zone of retina that
is drained by the obstructed or occluded retinal venule.  


















With the passage of months the cotton-wool spots disappear and with the passage
of months to years the hemorrhages and edema may also disappear although often
incompletely.  In certain eyes large patches of the retina may experience profound
loss of blood flow (“nonperfusion”).  In this situation the retinal may “grow” tiny new
vessels (retinal neovascularization) typically along the margin of the area of capillary
non-perfusion.  These new vessels are very fine, do not nourish the retina and are
prone to spontaneous rupture potentially leading to bleeding directly into the
normally clear gel (vitreous) that fills the center of the eye (in front of the retina and
behind the cornea and the lens).  This is known as a vitreous hemorrhage.  Rarely,
retinal neovascularization in the setting of BRVO develops into scar-like membrane
formation that may contribute toward the development of retinal detachment.  
Neovascularization developing on the surface of the optic nerve head occurs in
approximately 10% of BRVO eyes and neovascularization involving the retina
occurs in approximately 20% of BRVO eyes. Rarely, neovascularization can develop
on the surface of the iris and nearby structures that can result in elevation of eye
pressure and threaten damage to the optic nerve (neovascular glaucoma).
Neovascularization of the iris and neovascular glaucoma are uncommon and occur
in only approximately l% of affected eyes. Branch retinal vein occlusion accounted
for only 1.5% of a published series of 208 eyes with neovascular glaucoma from
multiple causes.



Age: Patients who are affected are usually in their fifth or sixth decade of life.
Frequency:
•        In the US retinal vein occlusions (branch and central) are the second most
common retinal vascular diseases after diabetic retinopathy.
•        In a population-based study from Australia, the Blue Mountains Eye Study, the
prevalence of BRVO in the population older than 48 years was 1.1%.
Race: No racial predilection for BRVO has been identified.
Risk Factors:
•        Systemic hypertension is a risk factor for BRVO.
•        Diabetes mellitus and open-angle glaucoma are inconsistent risk factors for
BRVO (in contrast to central retinal vein occlusion (CRVO) for which they are appear
to be stronger risk factors).
•        Moderate alcohol consumption reduces the risk of BRVO.
Sex: The incidence of BRVO for men = the incidence of BRVO for women.
Natural history: The degree of central vision loss after BRVO is highly variable.
•        The patient is usually aware of a painless decrease in visual acuity that may
occur suddenly or develop over a period of several days to several months.  Vision
loss is sudden in 75% of patients.  Patients often complain of misty or distorted
vision.
•        Visual acuity in BRVO eyes is not as severely affected as is the case for CRVO
eyes.  Forty-one percent of BRVO eyes will have an initial (examination) visual acuity
of 20/20 to 20/50, 25% of eyes will present with an acuity of 20/60 to 20/200, and 32%
of eyes will present with an acuity of 20/200 or worse.
•        However, if the macula (central retina) is not involved, there may be no visual
symptoms unless the patient notices altered peripheral vision.
•        Branch retinal vein occlusion involving both eyes can be found in
approximately 3% to 9% of patients.
•        60% to 100% of patients will have macular edema at some point in their clinical
course and approximately one-third of the patients followed for more than 1 year will
exhibit persistent macular edema.
Although data regarding the natural history of branch retinal vein occlusion is
incomplete, eyes suffering BRVO rarely go “blind”; most patients do experience at
least a modest degree of gradual visual improvement during the first 1 to 2 years
following their initial loss.  Finkelstein (1992) studied macular edema in a group of
patients with branch retinal vein occlusion who had a visual acuity of 20/40 or
worse.  He paradoxically found that eyes with macular ischemia (partial loss of blood
flow through the macular capillaries) showed a relatively greater frequency of
spontaneous improvement in visual acuity compared with eyes with good macular
perfusion (minimal impairment of blood flow through the macular capillaries). It
appears that macular edema arising as a complication of ischemia may be a
transient phenomenon, with visual improvement occurring as the edema resolves.  
In contrast, macular edema in eyes with good macular capillary perfusion frequently
persists, resulting in a persistent decrease in visual acuity.



BRVO patients are thought to have an predisposing anatomic factor such as “tight”
arteriole over venule crossing site(s) where the retinal arteriole compresses an
adjacent retinal venule. This compression leads to clot formation and subsequent
BRVO.  Inflammatory conditions that affect the retinal venules may also cause local
damage that predisposes the individual to blood clot formation with subsequent
BRVO.  Some of the inflammatory conditions reported in the literature are:
  • Sarcoidosis
  • Lyme disease
Thrombophilic (blood clot provoking) conditions:
  • Protein S deficiency
  • Protein C deficiency
  • Resistance to activated protein C (factor V Leiden)
  • Antithrombin III deficiency
  • Antiphospholipid antibody syndrome
  • Lupus erythematosus



The authors of the Branch Vein Occlusion Study (BVOS) recommended against
extensive testing in patients with typical BRVO.  However, certain laboratory studies
may be useful in atypical cases--those involving young patients, bilateral cases
(both eyes affected), or BRVO in patients with a strong personal or family history of
thromboembolism (blood clotting).  In such cases the following blood tests may be
helpful:
•        Prothrombin time (PT) and partial thromboplastin time (PTT)
•        Protein C, protein S, factor V Leiden, and antithrombin III
•        Homocysteine levels
•        Antinuclear antibody (ANA), lupus anticoagulant and anticardiolipin antibody
•        Serum protein electrophoresis

Imaging Studies:
•        Fluorescein angiography
A fluorescein angiogram may be obtained as soon as the hemorrhages have cleared
if the patient's vision is still diminished. This office-based test is usually done 3 or
more months after the event.  Angiography is used to determine the cause of central
visual loss (edema involving the central retina or macula vs. severe retinal capillary
damage involving the macula--“macular ischemia”).




















If angiography suggests that visual loss is secondary to macular edema with good
blood flow through the macular capillaries, laser photocoagulation in a “grid”
pattern may be of benefit. However, if angiography demonstrates the presence of
extensive macular ischemia, laser photocoagulation may not be very effective and
may therefore be withheld.
•        Optical coherence tomography
Given its ability to measure retinal thickness in a quantitative fashion, optical
coherence tomography (OCT) is a useful adjunct in the evaluation of patients with
macular edema secondary to BRVO.










Medical Care:
Systemic medical treatment is not effective in treating BRVO. In the past,
anticoagulants and fibrinolytic (blood clot destroying) agents have been used
without success.  In a major published retrospective review of retinal vein
occlusions by Hayreh (2011) from the University of Iowa Department of
Ophthalmology, the use of anticoagulants was shown to impair recovery of vision
owing to bleeding into the retina from compromised capillaries.  

In September, 2009 the Standard Care vs. Corticosteroid for Retinal Vein Occlusion
(SCORE) Study Group reported the results of a 2 year randomized prospective
clinical treatment trial which compared laser photocoagulation with intraocular
(“inside the eye”) corticosteroid (triamcinolone acetonide) injections at two dosages
(1mg. versus 4mgs.).  The primary outcome of the trial was an improvement of at
least 3 lines of vision on the EDTRS eyechart.  Twenty-nine percent of the laser
treated eyes, 26% of the 1 mg. injected eyes, and 27% of the 4 mg. injected eyes
achieved the primary outcome. The rates of elevated intraocular pressure and
cataract were similar for the laser treated eyes and 1 mg. injected eyes, but higher in
the 4 mg. injected eyes.  The SCORE Study concluded that there was no difference
identified in visual acuity at 12 months for the laser treated group compared with the
triamcinolone groups; however, rates of adverse events (particularly elevated
intraocular pressure and cataract) were highest in the 4 mg. group.  The SCORE
Study confirmed that macular laser photocoagulation remains the preferred
treatment option for macular edema arising as a visually significant complication of
branch retinal vein occlusion.

In 2010 Genentech reported the 12 month data from the BRAVO Study Group which
investigated the use of ranibizumab (Lucentis) in the treatment of branch retinal vein
occlusion (BRVO).  Patients were randomized to treatment with two different doses
of ranibizumab or sham injection.  Patients were administered injections monthly for
6 months and treated as needed for recurrent retinal edema in the second six
months.  Patients treated with 0.5 mg ranibizumab doses gained 2.5 times more
letters of acuity as tested by the ETDRS eyechart compared with sham treated
patients.  Recurrences of retinal edema and vision loss were encountered during the
second six months in the group of patients receiving ranibizumab requiring on
average nearly 3 additional medication injections in order maintain gains in
reduction of retinal edema and visual acuity.  Since the publication of the BRAVO
study, the use of ranibizumab (Lucentis) and bevacizumab (Avastin) have become
the preferred agents of choice for the management of severe macular edema in
BRVO patients especially when accompanied by retinal hemorrhages of confluence
that would make placement of laser burns difficult.  The use of macular laser
photocoagulation and/or use of intravitreal corticosteroids (not investigated by
BRAVO) following ranibizumab therapy may assist in promoting durability of
therapy.  

Ozurdex is an implantable corticosteroid pellet containing 0.7 mg of dexamethaxone
which dissolves over 2 to 3 months after injection into the vitreous cavity.  Six month
data from a pivotal treatment trial (GENEVA) in 2010 demonstrated a reduction in
branch retinal vein occlusion related retinal edema and statistically significant
number of letters gained in acuity on the EDTRS eyechart in patients treated with the
Ozurdex implant compared with sham injection eyes.  However, the number of
patients treated with Ozurdex gaining at least 3 lines of acuity of the ETDRS eyechart
was not statistically different from sham treated patients by the end of 6 months.  
Data in the second six month study which permitted re-injection of previously
Ozurdex treated patients and Ozurdex injection of sham patients from the first 6
month study suggested a trend toward continued improvement in the initial Ozurdex
treated group (and improvement in vision in the initial sham treated group) but the
benefit of treatment was probably blunted by the develop of steroid induced
cataract.  Intraocular pressure elevations were encountered in the Ozurdex treated
groups which peaked 2 months following implantation and fell to acceptably low
levels by 6 months following injection.   

































Surgical Care: BRVO usually has a relatively benign course. Nevertheless, certain
complications may develop requiring surgical management. These complications
include non-clearing vitreous hemorrhage (blood “staining” of the normally clear
vitreous gel) and retinal detachment.  Surgical removal of the vitreous—vitrectomy—
may be required to remove the cloudy vitreous, scar-like membranes (if present),
identify retinal tears and use surgical techniques to repair retinal detachments.  
Laser photocoagulation may also be performed during vitrectomy to make
neovascularization regress (shrink or go away).  Surgical strategies to directly
address BRVO have included loosening or cutting the sheath where arterioles
compress obstructed venules and injecting clot dissolving drugs directly into
obstructed retinal venules with tiny devices.  The results of such surgical studies are
incomplete and await comparison to the natural history of BRVO’s.

Laser Treatment:
•        Macular grid laser photocoagulation
Macular grid laser photocoagulation was shown to be effective for the treatment of
macular edema in the large prospective Branch Vein Occlusion Study (BVOS trial;
1984).  Subsequent to the BVOS and other studies, most retinologists recommend
observation for at least 3 months to see if the patient's vision will spontaneously
improve.  If no improvement occurs and if the retinal hemorrhages have substantially
cleared from the area of the macula, a fluorescein angiogram is usually performed in
the physician’s office. If the angiogram shows leakage in the area of the macula in
the absence of severe macular ischemia, laser treatment may be recommended if the
patient’s visual acuity is between 20/40 and 20/200. The BVOS demonstrated that
after 3 years of follow-up, 65% of laser treated eyes improved by 2 or more lines of
vision compared with 37% of control (untreated) eyes.  If the fluorescein angiogram
reveals severe macular capillary damage (nonperfusion or ischemia), laser therapy
may be deemed ineffective.  In such cases observation is recommended.
•        Scatter photocoagulation to the peripheral retina
Peripheral retinal laser photocoagulation is indicated when retinal
neovascularization is indentified during examination and/or during fluorescein
angiography.  Scatter laser photocoagulation to the “watershed” retina formerly
drained by the obstructed venule has been shown to significantly lower the
incidence of vision threatening vitreous hemorrhage












































































.
What causes a BRVO?
How common are Branch Retinal Vein Occlusions?
What  other diseases are associated with BRVO?
How are BRVO's evaluated and treated?
BRVO with retinal hemorrhages, cotton-wool spots and
edema (in the distribution of the retinal hemorrhages).  The
superior and central macula are involved.
optic nervehead
("optic disk")
<macula>
fluorescein angiogram of a BRVO involving the superior
macula with severe macular capillary non-perfusion, i.e.,
macular ischemia
<zone of capillary
non-perfusion or ischemia>
above left: color photo of BRVO involving superior macula
above right: corresponding fluorescein angiogram with "hyperfluorescence" corresponding to zone
of macular edema
below left; color photo of same eye BRVO many months later.  Note the resolution of the retinal
hemorrhages and cotton-wool spots.
below right: corresponding fluorescein angiogram of same eye BRVO many months later.  Note the
lack of "hyperfluorescence" suggesting resolution of macular edema.  No laser treatment has been
applied.
<zone of macular edema>
OCT scan: cross sectional
view of a normal macula
OCT scan: cross sectional view of
BRVO related macular edema
high resolution OCT scanner