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Key words: Retinal vein occlusion; Denition; Classication; Fluo-
rescein angiography; Optical coherence tomography
© 2016 The Author. Published by ACT Publishing Group Ltd.
Kolar P. Definition and Classification of Retinal Vein Occlusion.
International Journal of Ophthalmic Research 2016; 2(2): 124-129
Available from: URL: http: //www.ghrnet.org/index.php/ijor/article/
view/1499
INTRODUCTION
Retinal vein occlusion (RVO) was first described in 1855 by
Liebreich and in 1878 by Michel[1], who indicated that RVO was a
complication of systemic vascular status that can be observed on the
fundus of the eye. Disease was named as Apoplexia retinae. This type
of occlusion was later described as the central retinal vein occlusion
(CRVO). Leber, in 1877, and Oeller, in 1896, described branch retinal
vein occlusion (BRVO)[2,3].
There are three main types of retinal vein occlusion: central retinal
vein occlusion, hemicentral retinal vein occlusion and branch retinal
vein occlusion.
RVO is the second most common retinal vascular disease after
diabetic retinopathy. Studies in overall populations showed that its
prevalence varies from 5.2 to 16 per 1,000[4].
RVO is more prevalent in men than women and it is more frequent
in older people, over 65 years of age[4], and BRVO is four times more
common than CRVO[4].
The most recognized risk factors for RVO are age and systemic
vascular disorders. In over half of the cases, the age of onset is over
65 years. However, patients under 45 years of age can also develop
an RVO[5]. Systemic diseases such as hypertension, hyperlipidemia
and diabetes mellitus are strongly associated with the development
of RVO[6]. Further systemic risk factors are vascular cerebral stroke,
blood hyperviscosity and thrombophilia[6]. Cigarette smoking has
also been linked to RVO[7].
Ophthalmic risk factors for RVO are ocular hypertension and
glaucoma, lower ocular perfusion pressure and congenital and
Petr Kolar, MD, PhD, Associate Professor of Ophthalmology at
Masaryk University, University Eye Clinic of Masaryk University
and University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Re-
public
Correspondence to: Petr Kolar, MD, PhD, Associate Professor
of Ophthalmology at Masaryk University, University Eye Clinic of
Masaryk University and University Hospital Brno, Jihlavska 20, 625
00 Brno, Czech Republic
Email: pe.kolar@gmail.com
Telephone: +420 5 3223 3263
Fax: +420 5 3223 3406
Received: November 29, 2015
Revised: April 18, 2016
Accepted: April 20, 2016
Published online: June 28, 2016
ABSTRACT
Retinal vein occlusion is second most common retinal vascular
disease after diabetic retinopathy. A main cause of the retinal vein
occlusion is arterial disease when arterial stiffness affects neighboring
vein. There are three main types of retinal vein occlusion: central
retinal vein occlusion, hemicentral retinal vein occlusion and branch
retinal vein occlusion. Central retinal vein occlusion and hemicentral
retinal vein occlusion can be further divided into non-ischemic and
ischemic types. Branch retinal vein occlusion can be further divided
into major branch retinal vein occlusion and macular branch retinal
vein occlusion based on the location of the occlusion. Retinal vein
occlusion is a major cause of vision loss. Of the two main types of
retinal vein occlusion, branch retinal vein occlusion, is 4- to 6-times
more prevalent than central retinal vein occlusion. A common risk
factor for retinal vein occlusion is advancing age, and additional
risk factors include systemic conditions such as hypertension,
arteriosclerosis, diabetes mellitus, hyperlipidemia, vascular cerebral
stroke, blood hyperviscosity and thrombophilia. Ophthalmic risk
factors for retinal vein occlusion are ocular hypertension and
glaucoma, higher ocular perfusion pressure and changes in the retinal
arteries.
TOPIC HIGHLIGHT
Denition and Classication of Retinal Vein Occlusion
Petr Kolar
124
Int. J. Ophthalmic Res 2016; 2(2): 124-129
ISSN 2409-5680
Online Submissions: http://www.ghrnet.org/index./ijor/
doi:10.17554/j.issn.2409-5680.2016.02.35
International Journal of Ophthalmic Research
acquired changes in retinal arteries[8].
The natural course of RVO leads to a decrease in visual acuity
if the macula lutea is affected by retinal hemorrhages and macula
edema[8].
DEFINITION OF RETINAL VEIN OCCLUSION
RVO can be dened as aretinal vascular disorder characterized by
congestionand dilatation of the retinal veins with subsequentretinal
hemorrhages and edema, retinalischemia including cotton wool spots,
retinal exudatesand macular edema[9].
RVO is an occlusion of either the central retinal vein or a branch
of the retinal vein, and its pathogenesis is not completely understood.
The condition may be because of a combination of three systemic
changes known as Virchow’s triad (Figure 1), which includes
hemodynamic changes (venous stasis), degenerative changes of the
vessel wall and blood hypercoagulability[5,10]. Clinical features and
severity vary according to the location of the retinal vein closure.
Generally, patients with BRVO have a better prognosis than patients
with CRVO.
Until the introduction of anti-VEGF treatment, patients’ prognosis
for both conditions was poor. Many CRVO patients lose vision as
a result of ischemic complications such as secondary neovascular
glaucoma and macular edema.
CLASSIFICATION OF RETINAL VEIN
OCCLUSION
RVO can be classied into three main types, according to the affected
area on the retinal surface: CRVO, HCRVO and BRVO. BRVO is
more common than CRVO. In BRVO, a branch of the retinal venous
system is occluded, while in CRVO, the occlusion is located in the
central retinal vein[11-16]. BRVO is divided further into major BRVO
and macular BRVO. CRVO is divided into ischemic and non-
ischemic types[12,13]. And HCRVO, which involves only one-half of
the retinal surface and, similar to CRVO, it is divided into ischemic
and non- ischemic types[17].
According to the ischemic status, CRVO and HCRVO are divided
into ischemic and non-ischemic types. Ischemic CRVOs are less
common, accounting forone-third of CRVOs, and the other two-
thirds are non-ischemic CRVOs[13,18]. Retinal ischemia in RVO is a
strong prognostic factor, and patients whose eyes have large ischemic
zones have a worse prognosis than patients whose eyes have small
ischemic areas. Non-ischemic RVOs can progress to ischemic forms.
This progression is time dependent, with a progression rate of 33%
within 3 years[19]. Neovascular complications may arise in 50% of
patients whose eyes have ischemic CRVO in a 4-year period, despite
treatment with anti-VEGF[20]. Raised intraocular pressure and raised
erythrocyte sedimentation can be found in CRVO[7,8,17]. In opposite
hypermetropia, arteriosclerosis and hypertension are more common
in BRVO[7,8,17].
CENTRAL RETINAL VEIN OCCLUSION
Clinical findings in patients with CRVO depend on the degree of
central retinal vein occlusion, and the degree of venous congestion
is also important. A patient with a low degree of venostasis and good
visual acuity can be diagnosed, but there are patients with a high
degree of venostasis and poor visual acuity. The degree of venostasis
correlates well with visual acuity[21].
Ophthalmoscopic finding in the eye affected with CRVO
Kolar P. Denition and Classication of RVO
125
Figure 1 Virchow’s triad.
Figure 2 Color fundus image of non-ischemic central retinal vein
occlusion, venous dilatation and retinal hemorrhages are present.
includes signs of venous stasis. The venous system is dilated and
tortuous, and retinal hemorrhages are present in all four quadrants.
Hemorrhages are most often intra-retinal, but pre-retinal and sub-
retinal hemorrhages may also be present (Figure 2). Hemorrhages
are located predominantly on the posterior pole near the optic disc
and macula lutea. In ischemic CRVOs, hemorrhages are spread
throughout the retina, and a typical sign is swelling of the optic disc.
Hemorrhages usually cover the surface of the optic nerve.
Figure 2 Color fundus image of non-ischemic CRVO (original author
photo).
Basic signs of ischemia are cotton wool spots, retinal edema and
macular edema. Cotton wool spots have a typical white color and an
appearance like a cotton ball. Hard exudates are usually detected on
the edges of ischemic zones. They have a white or white-yellow color
and they are formed by accumulation of blood lipids.
In the acute phase of CRVO, the degree of ischemia is usually
high. This is related to low visual acuity because of macular edema.
In the chronic phase of CRVO, visual acuity decreases but not as
much as in acute CRVO. However, chronic occlusion is indicated by
the presence of neovascularization either on the iris or in the retina.
Gonioscopy can detect neovascularization in the iridocorneal angle.
According to the Central Retinal Vein Occlusion Study Group,
CRVO is divided into two major forms: non-ischemic and ischemic.
Classication of these two types of CRVO is based on uorescein
angiography (FA) nding. Non-ischemic CRVO is characterized by
less than 10 disc areas (DA) of ischemia presented on FA, with no
retinal neovascularization. The ischemic type of CRVO is the more
126
Kolar P. Denition and Classication of RVO
advanced type of RVO and it is characterized by either retinal or
iris neovascularization, with retinal ischemia greater than 10 DA on
FA.CRVOs with a large number of hemorrhages are recommended
to be classied as ischemic CRVOs[19]. Up to 83% ofnon-ischemic
CRVOs with large hemorrhages were later reclassied as ischemic
occlusions.
HEMICENTRAL RETINAL VEIN OCCLUSION
In 1980, Hayreh described HCRVO as a separate clinical entity[22].
Hedemon strated that during embryonic life, two trunks of the central
retinal vein exist, and one trunk usually disappears before birth.
However, in 20% of subjects, both trunks may persist[23]. HCRVO
involves occlusion of one of the two trunks, as described above. Half
of the retinal surface is thus affected by this occlusion.
Another clinical entity that can be interchanged with HCRVO was
found. It is hemicentral BRVO. Hemicentral BRVO is occlusion
of the major vein branch near the optic disc that may simulate
HCRVO[24]. Pathogenesis of both clinical entities is completely
different. HCRVO involves occlusion of one trunk of the central
retinal vein, while in hemicentral BRVO, the arterio-venous crossing
near the optic disc is occluded[16].
HCRVO is divided into ischemic and non-ischemic types, similar
to CRVO. These two types are distinguished in a manner similar to
that of CRVO. Non-ischemic HCRVO appears as ischemic zones
that are less than 10 DA on FA, while the ischemic type has ischemia
on more than 10 DA of the retinal surface. The ischemic type of
HCRVO is less common, representing 19% of cases, while non-
ischemic CRVO is present in 81% cases[23].
HCRVO clinical ndings are similar to those of CRVO, but only
one-half of the retinal surface is involved. HRCVO usually involves
the superior or inferior half of the retina. Retinal hemorrhages,
cotton-wool spots, retinal edema and hardexudates can be seen on
microscopic examination (Figure 3). Neovascularization on the iris
or retinal surface are subsequently detectable. Collaterals are detected
between two trunks of central retinal vein.
Figure 3. Color fundus image of non-ischemic HCRVO (with
courtesy of http: //retinagallery.com/).
The effect on visual acuity depends on the status of the macula
lutea. Visual acuity is poor in patients with HCRVO, whose eyes
have macular edema. The visual field is usually impaired in the
corresponding retinal areas.
BRANCH RETINAL VEIN OCCLUSION
BRVO affects branches of the central retinal vein. Hayreh divided
BRVO into two groups: major BRVO and macular BRVO[16].
Major BRVO involves occlusion of 1 of the 4 major retinal vein
branches, and it involves all retinal regions drained by this branch[16].
Macular BRVO arises from occlusion of the macular branch of the
retinal vein[16].
Figure 4. Color fundus image of macular BRVO (with courtesy of
http: //retinagallery.com/).
Figure 5. Color fundus image of major BRVO (original author
photo).
BRVO can be diagnosed in the nasal or temporal quadrants, or in
the superior or inferior retinal quadrants. Nasally-located BRVOs
are usually diagnosed incidentally because they are far away from
the macula and they do not affect visual acuity. They may manifest
as a vitreous hemorrhage from retinal neovascularization or as
secondary neovascular glaucoma that result from neovascularization
on the iris surface. Temporally located BRVOs usually affect the
Figure 3 Color fundus image of non-ischemic hemicentral retinal vein
occlusion, involvement of upper retinal quadrants.
Figure 4 Color fundus image of macular branch retinal vein occlusion,
lower part of macula luthea is involved.
Figure 5 Color fundus image of major BRVO, lower part of retina is
involved by edema and hemorrhages.
macula lutea, and they manifest as a decrease in visual acuity. Mainly
superotemporally-located BRVOs tend to spread across the macula
lutea because of the effect of gravity on the intra-retinal uid. Some
temporal BRVOs may be asymptomatic, similar to nasal BRVOs, if
they are located a large distance away in the peripheral retina.
A main characteristic of BRVO is venous dilatation peripherally
from the site of occlusion. Occlusion usually occurs on the arterio-
venous crossing. Both vessels have a common adventitia and the
retinal artery compresses the retinal vein. An additional characteristic
of BRVO is retinal hemorrhage. In severe cases, sub- or pre-retinal
hemorrhages may be seen. Retinal edema is also present in affected
areas, and if retinal ischemia is present, cotton-wool spots can be
detected. Hard exudates can also be detected in the transition to
ischemic and non-ischemic retina.
FA can detect vascular abnormalities and ischemic retinal areas,
and it can also detect macular edema.
An important imaging method is optical coherence tomography
(OCT). OCT is a non-invasive imaging test that uses light waves
to take cross-section pictures of the retina. It can detect retinal
edema, intra-retinal changes and cystoid remodeling of intra-retinal
structures. It can also monitor treatment success.
Patients with BRVO have a good prognosis[16,25,26], but prognosis
depends on several anatomical facts[9]: (1) localization of the
occlusion. Patients with peripherally-located BRVOs have a better
prognosis because of lack of macular involvement; (2) diameter of
the occluded retinal vein. A larger vessel diameter leads to formation
of more collateral circulation, and thereby better normalization of
compromised circulation; and (3) degree of venous occlusion. This
determines the degree of stasis in the retinal vasculature.
FLUORESCEIN ANGIOGRAPHY
FA is a useful diagnostic tool that can objectively evaluate retinal
circulation. To perform FA we used intravenously-applied uorescein
dye. Fluorescein does not leak from physiologically normal vessels,
but it does leak from vessels and capillaries affected by RVO leaks.
The amount of leakage depends on the severity of the occlusion.
In CRVO, retinal hemorrhages are seen as a block of uorescence.
Places that are less affected by hemorrhages present as either
uorescein leakage or as non-perfusion caused by retinal ischemia
(Figures 6, 7 and 8). Based on FA results, CRVO can be divided into
non-ischemic and ischemic types. The non-ischemic type has areas of
non-perfusion that are smaller than 10 DA in size, while the ischemic
type has non-perfusion areas that are greater than 10 DA.
Figure 6 Early FA image in non-ischemic CRVO (original author
photo).
Figure 7 Intermediate FA image in non-ischemic CRVO (original
author photo).
Figure 8 Late FA image in non-ischemic CRVO (original author
photo).
In the ischemic type, CRVOs are identified by retinal
neovasularization. On FA, uorescein leaks intensively in the early
phases in ischemic areas. FA distinguishes between retinal collaterals
and retinal neovascularization. The retinal collateral does not leak
dye, while neovascularization is identied by leaking dye. FA can
also detect therapeutic success in CRVO treatment. In successfully-
treated CRVO, leakage diminishes.
In HCRVO, the ndings are similar to those of CRVO, but only
one-half of retinal surface is affected. Similar to CRVO, FA can
detect ischemic or non-ischemic type of HCRVO. HCVO seems to
be a rare condition.
In BRVO, FA represents an essential diagnostic tool, similar to
that for CRVO and HCRVO, if there is any risk of development
of macular edema. Similar to CRVO and HCRVO, there are many
retinal hemorrhages that block fluorescence. When they disappear
retinal blood flow can be much more easily examined. Non-
perfused retinal areas can be detected and treated either by laser
photocoagulation or anti-VEFG treatment.
Figure 9 Early FA image of major BRVO (original author photo).
127
Kolar P. Denition and Classication of RVO
Figure 6 Early FA image in non-ischemic CRVO.
Figure 7 Intermediate FA image in non-ischemic CRVO.
Figure 8 Late FA image in non-ischemic CRVO.
Figure 10 Late FA image of major BRVO (original author photo).
Figure 11 Early FA image of macular BRVO (original author
photo).
Figure 12 Late FA image of macular BRVO (original author
photo).
OPTICAL COHERENCE TOMOGRAPHY
OCT is a non-invasive imaging test. OCT can easily detect pathology
in the retina and choroid on the posterior pole of the eye. This feature
can be used to diagnose RVO.
128
Kolar P. Denition and Classication of RVO
In the acute phases of CRVO and BRVO, retinal edema can
be detected if the posterior pole is affected. Macular edema is
often combined with macular hemorrhage, and is caused by intra-
retinal accumulation of fluid. In more advanced cases, sub-retinal
accumulation of fluid can be detected. OCT can efficiently detect
successful RVO therapy, which decreases the amount of retinal uid.
Figure 13 OCT image of diffuse macular edema in CRVO (original
author photo).
Although FA and OCT are important diagnostic tools for RVO,
some functional tests like electroretinography (ERG), visual acuity,
Figure 9 Early FA image of major BRVO.
Figure 10 Late FA image of major BRVO.
Figure 11 Early FA image of macular BRVO.
Figure 12 Late FA image of macular BRVO.
Figure 13 OCT image of diffuse macular edema in CRVO.
visual elds, relative afferent pupillary defect (RAPD), color doppler
imaging should play important role in diagnostics of RVO. They are
of great importance especially for differentiation of ischemic from
non-ischemic central retinal vein occlusion[11].
SUMMARY
RVO is the second most common retinal vascular disease after
diabetic retinopathy. The main systemic risk factors are systemic
hypertension, hyperlipidemia and diabetes mellitus. Men are more
often affected than women. The main ophthalmic risk factor for RVO
is glaucoma.
There are three main types of RVO: CRVO, HCRVO and BRVO.
CRVO is four times less common than BRVO, but patients with
CRVO have a worse prognosis.
CRVO and HCRVO can be further divided into the non-ischemic
and ischemic types. Their main difference is the amount of retinal
ischemia. The non-ischemic type has less than 10 DA of ischemia,
while the ischemic type has more than 10 DA of ischemia. Venous
system dilatation, retinal hemorrhage, retinal edema, cotton-wool
spots and hard exudates are clinical observations in CRVO and
HCRVO.
BRVO can be further divided into major BRVO and macular
BRVO, based on the location of the occlusion. Major BRVO affects
one of the four major branches of the central retinal vein, and macular
BRVO affects one of the macular branches ofthe central retinal vein.
Macular edema is more commonly present in macular BRVO, and
patients with an occlusion that is located peripherally have a better
prognosis then those with a central occlusion.Diagnostic tools such
as FA and OCT assist in the diagnosis and treatment of RVO.
129
Kolar P. Denition and Classication of RVO
COMPETING INTERESTS
The author declares that there is no conict of interest regarding the
publication of this paper.
REFERENCES
1 Michel J. Ueber die anatomischen Ursachen von Veranderun-
gendes Augenhintergrundesbeieinigen Allgemeinerkrankungen.
Deutsch Arch Klin Med 18 78; 22: 339-345.
2 Leber T. Die Krankheite der Netzhaut und des Sehnerven. In:
Graefe-Saemisch. Handbuch der Gesamten Augenheikunde.
Leipzig: Verlag von Wilhelm Engelmann; 1877: 551.
3 Oeller J. Atlas der Ophtlzaimoscopie. Wiesbaden, Germany: C.
Tabs XIII; 1896-1899.
4 Rogers S, McIntosh RL, Cheung N, Lim L, Wang JJ, Mitchell
P,Kowalski JW, Nguyen H, Wong TY; International Eye Dis-
easeConsortium. The prevalence of retinal vein occlusion: pooled
datafrom population studies from the United States, Europe, Asia,
andAustralia. Ophthalmology 2010; 117: 313-319.
5 Zhou JQ, Xu L, Wang S, Wang YX, You QS, Tu Y, Yang H, Jonas
JB. The 10-year incidence and risk factors of retinal vein occlu-
sion: The Beijing eye study. Ophthalmology 2013; 120: 803-808.
6 Mohamed Q, McIntosh RL, Saw SM, Wong TY.Interventions for
central retinal vein occlusion: anevidence-based systematic re-
view. Ophthalmology 2007; 114: 507-519.
7 Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology
ofretinal veinocclusion: the Beaver Dam Eye Study. Trans Am
OphthalmolSoc 2000; 98: 133-141.
8 Kolar P. Risk Factors for Central and Branch Retinal Vein Oc-
clusion: A Meta-Analysis of Published Clinical Data. Journal
of Ophthalmology 2014, Article ID 724780, 5 pages, 2014.doi:
10.1155/2014/724780.
9 Coscas G, Loewenstein A, Augustin A, Bandello F, Battaglia Par-
odi M, Lanzetta P, Monés J, de Smet M, Soubrane G, Staurenghi G.
Management of Retinal Vein Occlusion – Consensus Document
Ophthalmologica 2011; 226: 4-28
10 Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis,
visual prognosis, and treatment modalities. Curr Eye Res 2008;
33: 111-131.
11 Hayreh SS. Retinal vein occlusion. Indian J Ophthalmol 1994; 42:
109-132
12 Hayreh SS. Classication of central retinal vein occlusion. Oph-
thalmology. 1983 May; 90(5): 458-474
13 Hayreh SS. Differentiation of ischemic from non-ischemic central
retinal vein occlusion during the early acute phase. Graefes Arch
Clin Exp Ophthalmol. 1990; 228(3): 201-217
14 Hayreh SS, Zimmerman B, Podhajsky P. Incidence of various
types ofretinal vein occlusion and their recurrence and demo-
graphic characteristics. Am J Ophthalmol 1994; 117: 429-441.
15 Hayreh SS, Zimmerman MB. Fundus changes in branch retinal
vein occlusion. Retina 2015; 35: 1216-1227.
16 Hayreh SS. Prevalent misconceptions about acute retinal occlusive
disorders. ProgRetin Eye Res 2005; 24: 493-519.
17 Appiah AP, Trempe CL. Differences in contributory factorsamong
hemicentral, central, and branch retinal vein occlusions. Ophthal-
mology 1989; 96: 364-366.
18 Hayreh SS. Ocular vascular occlusive disorders: Natural history
of visual outcome. ProgRetin Eye Res. 2014; 0: 1-25.
19 CVOS-Group Natural historyand clinical management of central-
retinal vein occlusion. The Central Vein Occlusion Study Group.
Arch Ophthalmol 1997; 115: 486-491.
20 Brown DM, Wykoff CC, Wong TP, MarianiAF, Croft DE, Schuet-
zle KL et al. Ranibizumab in preproliferative (ischemic) central
retinal veinocclusion: the rubeosis anti-VEGF (RAVE) trial.
Retina 2014; 34: 1728-1735.
21 Feltgen N, Pielen A. Retinaler Venenverschluss. Epidemiologie,
Einteilungund klinische Befunde. Ophthalmologe 2015; 112 : 607-
620.
22 Hayreh SS, Hayreh MS. Hemi-central retinal vein occlusion.
Pathogenesis, clinical features, and natural history. Arch Ophthal-
mol 1980; 98: 1600-1609.
23 Chopdar A. Hemi-central retinal vein occlusion. Pathogenesis,
clinical features, natural history and incidence of dual trunk cen-
tralretinal vein. Trans OphthalmolSoc U K 1982; 102: 241-248.
24 Hayreh SS, Zimmerman MB. Hemicentral retinal vein occlusion.
Natural history of visual outcome. Retina 2012; 32: 68-75.
25 Rehak M, Wiedemann P. Retinal vein thrombosis: Pathogenesis
and management. Journal of Thrombosis and Haemostasis 2010; 8:
1886-1894.
26 Jaulim A, Ahmed B, Khanam T, Chatziralli IP. Branch retinalvein
occlusion: epidemiology, pathogenesis, risk factors, clinicalfea-
tures, diagnosis, and complications. An update of the literature.
Retina 2013; 33: 901-910.
Peer reviewers: Carolina Arruabarrena, Oftalmología, Hospital
"Príncipe de Asturias", Alcalá de Henares. 28805 Madrid, Spain;
Petia Kupenova, MD, PhD, Associate Professor, Department of
Physiology, Medical University-Soa, 1 G Soiski St, 1431, Soa,
Bulgaria.
