Hamid Fesharaki MD Eye department Isfahan University of medical sciences In the name of god Types of retinal venous occlusion Central retinal vein occlusion Branch retinal vein occlusion Hemi retinal vein occlusion ID: 699390
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Pathophysiology of retinal vein occlusion Hamid Fesharaki MD Eye department Isfahan University of medical sciences
In the name of godSlide2Slide3Slide4Slide5Slide6Slide7Slide8
Types of retinal venous occlusionCentral retinal vein occlusionBranch retinal vein occlusionHemi retinal vein occlusionSlide9
Branch Retinal Vein OcclusionThe ophthalmoscopic findings of acute BRVO include :superficial hemorrhages, retinal edema, and often cotton-wool spots (NFL infarcts) in a sector of retina drained by the affected vein . Branch retinal vein occlusions occur most commonly at an arteriovenous crossing.
The degree of macular involvement determines the level of visual impairment.
When the occlusion does not occur at an arteriovenous crossing, the possibility of an underlying retinochoroiditis should be consideredSlide10
The mean age for patients at the time of occurrence is their sixties.The obstructed vein is dilated and tortuous, and, with time, the corresponding artery may become narrowed and sheathed. The quadrant most commonly affected is the superotemporal (63%); nasal vascular occlusions are rarely detected clinically.
A variant of BRVO based on congenital variation in central vein anatomy may involve either the superior half or inferior half of the retina (hemispheric or hemi central retinal vein occlusion
Branch Retinal Vein OcclusionSlide11
Branch Retinal Vein OcclusionThe Eye Disease Case-Control Study identified the following abnormalities as risk factors for the development of BRVO:
. history of systemic arterial hypertension .
cardiovascular disease . increased body mass index at 20 years of age .history of glaucoma.
Diabetes mellitus was not a major independent risk factor.Slide12
Branch Retinal Vein OcclusionHistologic studies suggest that: common adventitia binds the artery and the vein together at the arteriovenous crossing and that thickening of the arterial wall compresses the vein resulting in turbulence of flow, endothelial cell damage, and thrombotic occlusion.Slide13
Branch Retinal Vein OcclusionThe thrombus may extend histologically to the capillary bed. Secondary arterial narrowing often develops in the area of occlusion. Visual prognosis in BRVO is most closely related to the extent of capillary damage and retinal ischemia in the maculaSlide14
Non-perfused BRVOSlide15
Branch Retinal Vein Occlusion. Fluorescein angiography is used to assess the extent and location of retinal capillary nonperfusion. The integrity of the parafoveal capillaries is an important prognostic factor for visual recovery.
Vision may be reduced in acute cases from macular edema, retinal hemorrhage, or perifoveal retinal capillary occlusion.
The hemorrhage resolves over time, and capillary compensation and collateral formation may permit restitution of flow with resolution of the edema and improvement in visual function. In other eyes, however, progressive capillary closure may occur.Slide16
Ischemic BRVO with NeovascularizationSlide17
Branch Retinal Vein OcclusionExtensive retinal ischemia (greater than 5 disc diameters) results in neovascularization from the retina or optic nerve in approximately 40% of eyes, and 60% of such eyes will develop
preretinal bleeding if laser photocoagulation is not performed. Overall, approximately 50%-60% of patients with all types of BRVO will maintain visual acuity of 20/40 or better after 1 year.Slide18
Ischemic BRVO with neovascularizationSlide19
Retinal vasculitis with BRVOSlide20
Retinal Vasculitis with Hemorrhages and Cotton Wool SpotsSlide21
Dilated and tortuous Retinal veins swollen optic disc
intraretinal hemorrhages
Retinal edema
Central retinal vein occlusionSlide22
Type 1 CRVO: A mild, nonischemic form sometimes referred to as partial, perfused, or venous stasis retinopathySlide23
Mild (nonischemic) CRVO is characterized by good visual acuity, a mild afferent pupillary defect, and mild visual field changes. Funduscopy shows mild dilation and tortuosity of all branches of the central retinal vein as well as dot-and-flame hemorrhages in all quadrants of the retina
Nonischemic CRVOSlide24
Nonischemic CRVOMacular edema with decreased visual acuity and mild optic disc swelling may or may not be present. If disc edema is prominent in younger patients, a combined inflammatory and occlusive mechanism may be present that has been termed
papillophlebitis.
Fluorescein angiography usually demonstrates prolongation of the retinal circulation time with breakdown of capillary permeability but minimal areas of nonperfusion.
Anterior segment neovascularization is rare in mild CRVO.Slide25
Fluorescein Angiography
A mild increase in retinal circulation time.
marked delay in arteriovenous transit time, which is longer than 20 seconds, masking by retinal haemorrhages
vessel wall staining.
Late staining along the large retinal veins is a characteristic finding in moderate and severe degrees of central retinal vein obstruction.
Nonischemic CRVOSlide26
Partial Central Retinal Vein Occlusion V Papillophlebitis ODSlide27
Pathophysiology of CRVOHistologic studies suggest that most forms of CRVO have a common mechanism:thrombosis of the central retinal vein at and posterior to the level of the lamina cribrosa.
In some instances, an atherosclerotic central retinal artery may impinge on the central retinal vein, causing turbulence, endothelial damage, and thrombus formation.
central retinal artery and vein share a common adventitial sheath as they exit the optic nerve head and pass through a narrow opening in the lamina cribrosa.Slide28
Type 2: Ischemic CRVOis characterized by at least 10 disc areas of retinal capillary nonperfusion on posterior pole view fluorescein angiography
also known as nonperfused, complete, or
hemorrhagic retinopathySlide29
Ischemic CRVOSlide30
Ischemic CRVO
Ischemic CRVO is characterized by rapid onset venous obstruction resulting in decreased retinal perfusion
severe visual loss
usually less than 20/400
marked afferent pupillary defectSlide31
Ischemic CRVOVariable numbers of cotton-wool spots are frequently found as well The visual prognosis is generally poor in ischemic CRVO, with approximately 10% of eyes achieving vision better than 20/400
The incidence of iris neovascularization is high (up to 60%)Slide32
Ischemic CRVOSlide33
Because of this
narrow entry in the lamina cribrosa
, the vessels are in a tight compartment with
limited space
for displacement. This anatomical position predisposes to thrombus formation in the central retinal vein by various factors:
Ocular compression of the vein:
changes in lamina cribrosa
glaucomatous cupping
inflammatory swelling in optic nerve
orbital compression
Virchow's triad for vascular occlusion
1.Hemodynamic disturbances : hyperdynamic or sluggish circulation
2. Vessel wall changes: vasculitis, endothelial damage, arteriosclerosis
3. Changes in the blood: deficiency of thrombolytic factors, increase in clotting factors
Pathophysiology of CRVOSlide34
Occlusion of the central retinal vein leads to: backup of the blood in the retinal venous system and increased resistance to venous blood flow. stagnation of the blood and
ischemic damage to the retina.
It has been postulated that ischemic damage to the retina stimulates increased production of vascular endothelial growth factor
(VEGF)
in the vitreous cavity. Increased levels of VEGF stimulate neovascularization of the posterior and anterior segment (responsible for secondary complications of CRVO).
It has been shown that VEGF causes capillary leakage leading to macular edema
which is the leading cause of visual loss in both ischemic CRVO and nonischemic CRVO.
Pathophysiology of CRVOSlide35
Pathophysiology of CRVOUnusual diseases that affect clotting mechanisms and blood viscosity may be associated with a CRVO-like picture Examples include:
blood dyscrasias (polycythemia vera), dysproteinemias, and causes of vasculitis (eg, sarcoidosis, systemic lupus erythematosus), and such hypercoagulable conditions as hyperhomocysteinemia, protein S deficiency, and protein C deficiency.
Oral contraceptives and diuretics have been implicated in CRVO.
Slide36Slide37
IschemiC RVOSlide38Slide39
CRVO Systemic risk factorsPatients may have premonitory symptoms of transient obscuration of vision prior to overt retinal manifestations. Systemic associations noted in the Eye Disease Case-Control Study include :
systemic arterial hypertension
diabetes mellitus open-angle glaucoma
Increased intraorbital pressure is a
rare but potentially important cause of central vein
hyperlipidemia
?Slide40
Pathophysiology of CRVOhyperviscosity retinopathy can mimic a typical CRVO. However, the retinal findings in hyperviscosity retinopathy are generally bilateral and usually related to dysproteinemia such as Waldenstrom macroglobulinemia or multiple myeloma
Diagnostic testing includes serum protein electrophoresis and measurements of whole blood viscosity.
In many cases, the hyperviscosity can be reversed by plasmapheresis.Slide41
Ischemic CRVOSlide42
Persistent cystoid macular edema in CRVOSlide43
Hemi retinal vein occlusionSlide44
Hyperviscosity retinopathy of high altitudeSlide45
Hyperviscosity retinopathy Slide46
CRVO due to Retinal vasculisSlide47
Toxoplasma Fulminate retinochoroiditisSlide48
Retinal vasculitis due to lupusSlide49
Shaken Baby SyndromeSlide50
Hematological disorders and other systemic conditions
Conditions that lead to increased
blood viscosity
such as
myeloproliferative
disorders are uncommon but known to be associated with CRVO.
Similarly, a number of
rare systemic inflammatory disorders causing systemic
vasculitis
(such as
Behçet’s
disease and
polyarteritis
nodosa
) also cause retinal vasculit
is leading to RVO, especially in the younger age group. The cause and management of the RVO here is closely linked to the underlying systemic disease and its management.
Thrombophilia
refers to the propensity to develop thrombosis (usually venous) due to
an
abnormality in the coagulation system
. This can be congenital (eg, Factor V Leiden, hyperhomocysteinemia or protein C, protein S and
antithrombin
deficiencies) or
acquired (eg, antiphospholipid syndrome), and its importance is potentially greater in the younger age group.
However
Fegan’s
review on CRVO and thrombophilia
14
suggested that there was a lack of consistency between studies in showing a valid association between CRVO and protein C, protein S and
antithrombin
III deficiency, and factor V Leiden/activated protein C resistance
.
In the antiphospholipid syndrome (APS) antibodies to
phospholipid
activate the coagulation cascade leading to both arterial and venous thrombosis.
Tests can be done to either detect the antibody (using the
anticardiolipin
antibody assay) or its effect on coagulation using a test for lupus anticoagulant. Up to 8% of patients with APS have ocular manifestations and
4 of 8 studies reviewed by Fegan
14
showed a significant association of APS in CRVO.
Further studies are required to determine the strength of association between APS and RVO.
Homocysteine
is a naturally occurring amino acid not found in protein. There are many causes for
hyperhomo-cysteinemia
(including rare enzyme deficiencies leading to
homocystinuria
) which predisposes to both arterial and venous thrombosis.
14
Several studies have questioned the validity of carrying out exhaustive tests for
thrombophilia
in RVO in the absence of a suggestive medical history. However their results have shown notable evidence of an association of hyperhomocysteinemia with CRVO sufficient to recommend the benefit of checking for hyperhomocysteinemia, which is correctable with folic acid and vitamins B6 and B12 supplements.
14
–
17
On current evidence it would be reasonable to not recommend general
thrombophilia
screening for all patients with RVO, but to reserve it for older patients with a past history of
thromboembolic
events and in young patients without any other general risk factors.Slide51
ConclusionThe Exact mechanism is nor knownSystemic:1. Vessel wall2. Hemodynamic3. Blood
Ocular:GlaucomaAnatomicalSlide52
Hyperviscosity retinopathy
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Types 3 CRVOAn intermediate form also exists, but more than 80% of these eye progress to the severe ischemic form.Slide56Slide57
Pathophysiology of RVO
Thrombosis within a retinal vein as described earlier will lead to a partial obstruction of blood flow within the vein and from the eye. The subsequent increased
intraluminal
pressure, if sufficiently high, will cause transudation of blood products into the retina according to Starling’s law. This will result in increased interstitial (retinal) fluid and protein. The latter will increase the interstitial
oncotic
pressure which will impede capillary perfusion and lead to ischemia. As stated by
Campochiaro
et al
21
this ischemia is not an all or none dichotomy, as those patients classified as nonischemic will still have varying degrees of retinal ischemia.
It is well recognized that inflammation affects the progression and outcome of
vitreoretinal
disease including retinal vein occlusion.
22
Yoshimura et al
22
have found significantly elevated vitreous levels of the soluble cytokines interleukin (IL) 6 and 8,
monocyte
chemoattractant
protein-1, and vascular endothelial growth factor (VEGF) in RVO, and especially in CRVO.
Funk et al
23
have also demonstrated
elevated aqueous levels of these same factors in patients with CRVO when compared with control samples. The exact interaction of these factors remains speculative but an understanding of the roles that VEGF fulfils is increasing. It is induced by tissue hypoxia such as retinal ischemia and acts as an
angiogenic
and
vasopermeable
factor on endothelial cell membrane bound receptors with tyrosine
kinase
activity.
24
Ozaki et al
25
have demonstrated that the
implantation of slow release pellets of human recombinant VEGF into the vitreous cavity of rabbits and primates leads to retinal vessel dilatation, breakdown of the blood retinal barrier and retinal new vessel formation.
Noma
et al have reported elevated aqueous and vitreous levels of VEGF and IL-6 in patients with BRVO
26
,
27
and CRVO,
28
,
29
compared to controls. The levels of VEGF and IL-6 correlated with both the severity of macular edema and extent of retinal ischemia (capillary nonperfusion).
It is likely that the sudden retinal ischemia that occurs in BRVO and more so in CRVO will induce excessive VEGF production. VEGF is produced by the retina from retinal pigment epithelial cells, endothelial cells, and Muller cells, as well as other types of ocular tissue.
22
Boyd et al found a
close correlation between aqueous VEGF levels and the course of iris neovascularization and vascular permeability in patients with ischemic CRVO.
30
The excessive vascular permeability induced by VEGF will likely contribute to the macular edema that also occurs according to Starling’s law as described above. It is tempting to theorize that even if the primary venous obstruction was overcome (eg, via collateral formation), the macular edema can persist for much longer due to a self perpetuating cycle of VEGF-induced vascular permeability leading to macular edema, capillary damage, and retinal ischemia, stimulating further release of VEGF and other inflammatory cytokines leading to chronic macula edema.Slide58Slide59Slide60Slide61Slide62Slide63Slide64Slide65Slide66Slide67Slide68Slide69Slide70Slide71
ccacSlide72Slide73
Fundus autofluorescence can detect, in patients with recent-onset CRVO, a perivenular hypoautofluorescence with a fern-like appearance. Slide74Slide75Slide76Slide77Slide78Slide79Slide80
Retinal Vasculitis due to Lupus
Systemic Lupus Erythematosis
- Vasculitis