3. Introduction
• Common vascular disorder
• 2nd most common cause of blindness after
Diabetic retinopathy
• Cause ….obstruction to venous flow
• Associated risk factors: Multifactorial
• Classification
• -Site of involvement
• -Extent of retinal perfusion
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4. Demographics
• InAustralia,prevalenceof RVO…
– 0.7%inptsaged49-60yearsto4.6%inptsolder than80
years a
• Seasonalvariationfound…greaterthan20,000patientsinthe
monthofJanuary
a. MitchellP, SmithW, ChangA. PrevalenceandassociationsofretinalveinocclusioninAustralia.TheBlueMountainsEye
Study.Arch Ophthalmol. Oct 1996;114(10):1243-7
b. HoJD,TsaiCY, LiouSW, etal.Seasonalvariationsintheoccurrenceofretinalveinocclusion:afive-year nationwidepopulation-
basedstudyfromTaiwan.Am J Ophthalmol. Apr 2008;145(4):722-728.
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5. Common mechanism
Severe non perfusion leads to edema
Edema / hemorrhages
Dysfunction leakage of fluid and blood
Back pressure on capillaries endothelial junction
Venous blockage
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6. Predominant associations
• Royalcollegeofophthalmologistsguidelines:Feb. 2009
Patient
Group
NoObvious
Cause
Age<50
yrs
40%
Age>50
yrs
21%
Asian 10.7%
West
Indian
8.3%
Recurren
tcases
Hypertensio Hyperlipidemia Diabetes
n Mellitus
25% 35% 03%
64% 34% 4-15%
64% 50% 29%
83% 33% 38%
88% 47% 3%
6%
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25. CENTERAL RETINAL VEIN OCCLUSION
• It is more common than the artery occlusion.
• It typically affects > 6th or 7th decade of life.
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26. Etiology
• 1. Pressure on the vein by a sclerotic retinal artery
where the two share a common adventitia (e.g., just
behind the lamina cribrosa and at arteriovenous
crossings).
• 2. Hyperviscosity of blood as in polycythemia,
hyperlipidemia and macroglobulinemia.
.
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27. • 3. Periphlebitis retinae which can be central or
peripheral.
• 4. Raised introcular pressure. Central retinal vein
occlusion is more common in patients with
primary open-angle glaucoma.
• 5. Local causes are orbital cellulitis, facial
erysipelas and cavernous sinus thrombosis
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29. Central retinal Vein occlusion
• Painlesslossof vision
• Site:occlusionatorposteriortolamina
cribrosa
• Twoclinicaltypes
– IschemicCRVO(I-CRVO)
– Non-ischemic (NI-CRVO)
• ‘Research into CRVO is fraught with challenges, from
accurate disease classification to its treatment; even the
most prestigious trials have become controversial’
• MadhusudhanaKC,NewsomRS.Centralretinalveinocclusion:thetherapeuticoptions.CanJOphthalmol.Apr2007;42(2):193-5.
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30. Demographics
• NI-CRVO morecommonthanI-CRVO
• Noracial predilection
• Men> women
• >90%CRVO occursin> 50yrs age
a KleinR etal.Theepidemiologyofretinalveinocclusion:theBeaverDamEyeStudy.TransAmOphthalmolSoc2000;98:133–41. b
MitchellPetal.PrevalenceandassociationsofretinalveinocclusioninAustralia.TheBlueMountainsEye Study. Arch
Ophthalmol1996;114:1243–7.
c KleinR etal.The15-yearcumulativeincidenceofretinalveinocclusion:theBeaverDamEye Study.Arch
Ophthalmol. Apr2008;126(4):513-8.
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31. Non-ischaemic CRVO (venous stasis Retinopathy)
Most common clinical variety (75%).
Characterized by mild to moderate visual loss.
Fundus examination
In early cases :Mild venous congestion and tortuosity, a few
superficial flame-shaped hemorrhages more in the peripheral
than the posterior retina,
In late stage (after 6-9 months) : Mild papilloedema and mild or no
macular oedema. There appears sheathing around the main
veins, and a few cilioretinal collaterals around the disc. Retinal
haemorrhages are partly absorbed. Macula may show chronic
cystoid oedema in moderate cases or may be normal in mild
cases.
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33. Treatment
is usually not required.
The condition resolves with almost normal vision in
about 50 percent cases.
Visual loss in rest of the cases is due to chronic
cystoid macular oedema, for which no treatment is
effective.
However, a course of oral steroids for 8-12 weeks
may be effective.
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34. Ischaemic CRVO (Hemorrhagic retinopathy)
1. Acute (sudden) complete occlusion of central retinal
vein.
2. It is characterized by marked sudden visual loss.
Fundus examination in early cases:
1. Massive engorgement,
2. Congestion and tortuosity of retinal veins,
3. Massive retinal hemorrhages (almost whole fundus is full of
hemorrhages giving a ‘splashed-tomato’ appearance),
4. Numerous soft exudates, and papilledema.
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35. • Macular area is full of hemorrhages and is severely
edematous.
• In late stages:
• Marked sheathing around veins &collaterals is seen
around the disc.
• Neovascularisation may be seen at the disc (NVD) or
in the periphery (NVE).
• Macula: shows marked pigmentary changes and
chronic cystoid oedema.
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36. Complications
• Rubeosis iridis
• Neovascular glaucoma (NVG) (occur in more than 50 percent cases within 3
months (so also called as 90 days glaucoma).
• A few cases develop vitreous hemorrhage & proliferative
retinopathy.
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37. Natural history of CRVO
• NI-CRVO
– Completelyresolution…10% a
– ME resolves…30%in6-15 monthsb
– About50%...VAis6/60 orworse a
– 1/3rd progressto I-CRVO in6-12 monthsa
– Neovesselsdevelop…33%in12-15 months b
a. Central Vein Occlusion Study Group. Baseline and early natural history report. Arch Ophthalmol. Aug 1993;111(8):1087-95
b. McIntoshRL etal.NaturalHistoryofCentralRetinalVeinOcclusion:AnEvidence-BasedSystematicReview.Ophthalmology
2010;117:1113–1123
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38. Treatment
• Panretinal photocoagulation (PRP) or cryo-application, if the
media is hazy, may be required to prevent neovascular
glaucoma in patients with idespread capillary occlusion.
Photocoagulation should be carried out when most of the
intraretinal blood is absorbed, which usually takes about 3-4
months.
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39. (2) Branch retinal vein occlusion (BRVO)
• It is more common than the central retinal vein
occlusion.
• It may occur at the following sites: main branch at the
disc margin causing hemispheric occlusion, major
branch vein away from the disc,
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40. 1. AT A-V crossing causing quadrantic occlusion and
small macular or peripheral branch occlusion.
2. In BRVO oedema and haemorrhages are limited to
the area drained by the affected vein Vision is
affected only when the macular area is involved.
3. 2nd ry glaucoma occurs rarely in these cases.
4. Chronic macular oedema and neovascularisation
may occur as complications of BRVO in about 1/3
cases.
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41. Treatment
• Grid photocoagulation may be required in
patients with chronic macular oedema. In
patients with neovascularisation, scatter
photocoagulation should be carried out.
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53. • Systemictreatment a
– Anticoagulants…Heparin, warfarin
– Fibrinolyticagents…Streptokinase,tissue
plasminogen activator
– Antiplatelets…Aspirin, prostacyclin
– Hemodilution
• Nofavorableeffectsonnaturalhistory b
a MahmoodT. CRVO: currentmanagementoptions.PakJOphthalmol2009.25(1):56-9.
b Mohamed Q etal. interventionsfor CRVO. an evidence-basedsystematic review. Ophthalmology. 2007; 114:507-19
Treatment
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54. Medical treatment:
• In hypercoagulopathy – anticoagulant may be given, (no
role in prevention and management in most cases). So
generally not indicated
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55. Laser treatment:
BRVO study for macular edema:
• Argon laser photocoagulation (grid pattern) may reduce visual
loss from macular edema
Results in thinning of retina (outer retina)
Reducing oxygen consumption and increasing choroidal
delivery of oxygen to the inner retina
Produces auto regulatory constriction of the retinal vasculature in
the leaking area
decreases the edema
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56. • Wait 3 – 6 months before considering laser therapy.
• If the vision is reduced to 20/40 or worse, wait 3 – 6
months for sufficient clearing if retinal hemorrhage to
permit high quality FAand then evaluate for macular
edema and macular ischemia
• If perfused macular edema accounts for the vision loss
and vision continues to be 20/40 or worse without
spontaneous improvement consider grid macular
photocoagulation
• If macular ischemia accounts for the visual loss no laser
treatment is recommended.
General guideline from BRVOS for Macular edema
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57. •For grid treatment – argon blue green wavelength is
used
•Krypton red and argon green are absorbed less than
blue green by the xanthophyll pigment of the inner
retina that is present in increased concentration close
to the foveal center.
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58. BRVOS for new vascularization
• Prophylactically scatter laser photocoagulation can lessen
subsequent neovascularization complications
• If neovascularization already exists that laser can lessen
subsequent vitreous hemorrhage
• But it is recommended that laser be applied
only after neovascularization is observed
• BRVOS – strongly suggests that laser after development of
neovascularization is as effective in preventing vitreous
hemorrhage as is laser before the development of
neovascularization
• After laser vitreous hemorrhage incidence reduced from 60 %
to 30%
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59. Steroidtreatment
SCORE study (standard care vs corticosteroid for retinal vein
occlusion study)
• Effective and safety of intravitreal triamcinolone acetate for
the treatment of macular edema
• IVTA not recommended as 1st line therapy for macular edema in
BRVO. However can be considered if laser or anti VEGF are
ineffective
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60. GENEVA study (Global evaluation of implantable dexamethasone in
retinal vein occlusion with macular edema in BRVO and CRVO.
• Dexa implant is an alternative treatment to macular grid laser
in the appropriate patient (i.e. no glaucoma and
pseudophakic)
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61. Anti VEGF
retinal
ischemia
secretion of
VEGF
increased
vascular
permeability
vasodilatation
migration of
endothelial cells
and
neovascularization
Increased vascular
permeability
and vasodilatation
leads to retinal
edema
BRAVO (Branch retinal vein occlusion study)
• Efficacy and safety of ranibizumab in the treatment of macular edema from BRVO
• Study shows ranibizumab is superior to traditional laser for the treatment of
macular edema
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62. Current recommendation
Macular edema from BRVO
Monthly injection of 0.5mg
Ranibizumab If treatment fails after 3 months
Traditional grid macular laser
If capillary non perfusion
explains vision loss then
laser is not indicated)
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64. Surgical management
Vitrectomy with or without sheathotomy
• Removal of the compressive factor by sectioning the
adventitial sheath may be effective
• Due to risk of intraoperative complications and availability of
less invasive alternatives this is not indicated as 1st line
treatment
• Vitreous surgery: in non clearing vitreous hemorrhage,
epiretinal membranes or TRD with macular involvement
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66. Epidemiology
• M:F – equal
• More above 65 years old
• Prevalence in population based study: 0.1 – 0.4%
• Usually U/L disease but may develop RVO in fellow eye in 1 %
patient within 1 year and estimated 7 % of patient within 5
years
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67. Associations and risk factors with CRVO:
• Systemic vascular disease: DM, HTN, carotid insufficiency
• Ocular disease: POAG, ischemic optic neuropathy,
pseudotumor cerebri, tilted optic disc, optic nerve head
drusens
• Hematological alterations: hyperviscocity syndromes
(polycythemia vera, lymphoma, leukemia, sickle cell disease),
anemia, elevated plasma homocysteine, factor XII def,
antiphosphilipid antibody syndrome, protein c and s
deficiency.
• Inflammatory/autoimmune vasculitis: SLE
• Medications: oral contraceptions, diuretics, Hep B vaccine
• Infectious vasculitis: HIV, syphilis, herpes zoster, sarcoidosis
• Others: after retrobulbar block, dehydration, pregnancy
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68. Clinical features
• Sudden painless loss of
vision
• Hemorrhage radiate from the
optic nerve head are variable
in quantity and may result in
the classic “blood and
thunder” appearance
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69. • Cilioretinal artery occlusion can occur in association with CRVO
Together these occlusion have been hypothesized to constitute a
distinct clinical entity arising from a sudden increase in the
intraluminal capillary pressure due to CRVO
Inducing relative occlusion of the cilioretinal artery whose
perfusion pressure is lower than the central retinal artery
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70. CVOS
• VA at the time of presentation was variable but an
important prognostic indicator of final visual outcome
• Of those initial VA 20/40 or better – majority maintain VA
• Intermediate VA (20/50 to 20/200) – variable outcome
• Poor VA at onset (20/200 or less) – 20% chance of
improvement
• In CVOS – worse VA correlated with development of
NVI/NVA
• NVA may be present without NVI in 12%.
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71. Perfusion status
• CVOS classified perfusion status of CRVO – perfused, non
perfused or indeterminate based on FA characters
Perfused CRVO (non ischemic/incomplete/partial)
• Demonstrates less than 10 disc areas of retinal capillary
nonperfusion on FA
• These eyes typically have less intraretinal hemorrhage and
better initial VA
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72. Non perfused CRVO (ischemic/hemorrhagic/complete)
• Demonstrates 10 or more disc areas of retinal capillary
nonperfusion on FA
• Greater degree of intraretinal hemorrhage, macular and disc
edema and worse VA at onset
Indeterminate:
• When there is sufficient intraretinal hemorrhage to
prevent angiographic determination of perfusion
status.
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73. Other examination features that may help in determining the
perfusion status in the acute phase of CRVO include:
• Baseline VA
• RAPD
• Electro-retinography (negative wave form is seen)
• Goldmann perimetry
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74. CVOS classification of initial perfusion status of the
CRVO was important for determining the natural history
of the disease
• Poor VA and larger areas of non perfusion – Increased risk of
NVI/NVA
• Perfused – 10% chance of NVI/NVA
• Non perfused or indeterminate: 35% chance of NVI/NVA
• At 3 years – 45% chance of developing neovascular
glaucoma after onset of ischemic CRVO
• Overall – 34% of initially perfused eyes converted to non
perfused after 3 years.
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76. Within the retrolaminar portion of optic nerve
Central retinal artery and vein are aligned parallel to each
other in common tissue sheath
CRA and vein are naturally compressed as they cross the rigid
shieve like openings in the lamina cribrosa but typically gives
off branching collaterals vessels just piercing the lamina
These vessels may compress from mechanical stretching of
lamina as with increase in IOP which may cause a post bowing
of the lamina and subsequent impingement on the vein
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77. • Furthermore, local factors may predispose to occlusion of
veins, including compression by an atherosclerotic central
retinal artery or primary occlusion of the central retinal vein
from inflammation
• Hemodynamic alterations: produce stagnant flow and
subsequent thrombus formation in the CRV including
diminished blood flow, increased blood viscocity and an altered
lumen wall (Virchow’s triad)
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78. • In experimental trial – occlusion of both retrolaminar CRA and
vein posterior to lamina and prior to the branching of collateral
channels from the main trunk was required to produce
ischemic CRVO
• It is hypothesized that a non ischemic CRVO may be due to
occlusion of the CRV at a site further posterior, allowing normal
collateral channels to provide alternatives routes of venous
drainage
• Neovascularization of the anterior and posterior segment and
severity of macular edema are modulated by growth factors
released from ischemic retina.
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79. Treatment
• Treatment of CRVO is directed at treating the sequelae of
CRVO particularly macular edema and neovascularization
Treatment of systemic medical conditions
if any:
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80. Treatment of macularedema
• CVOS – grid laser photocoagulation not recommended
Corticosteroid therapy
• Maintain anti-inflammatory effects with modulation of production
of cytokines and growth factors including VEGF
• Also thought to stabilize BRB with reduction of vascular
permeability
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81. Score
• Showed significant improvement in VA with intravitreal
triamcinolone compared to observation
• The limited duration of the response to IVTA therapy has
prompted the development of sustained release steroids
(intravitreal fluocinolone acetonide)
• But with sustained release all phakic pt developed visually
significant cataracts and 92% developed increase IOP
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82. Intra vitreal Anti VEGFtherapy
VEGF
cause capillary endothelium cell proliferation
Progressive vascular closure and non perfusion in
CRVO
• Anti VEGF – enhance blood flow, lower intravenous
pressure and normalize venous diameter and tortuosity.
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83. Treatment of ocularneovascularization
Laser photocoagulation:
• CVOS recommends PRP be delivered promptly after the
development of NVI/NVA but not prophylactically in eyes with
nonperfused CRVO
• In 90% cases, NVI/NVA resolve in 1 to 2 months
after PRP Persistent neovascularization after PRP
Close observation
Additional PRP may be applied to halt its progression.
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84. • Patient with NVD/NVE without NVI/NVA should be treated with
PRP to prevent anterior segment neovascularization
Medical therapy
• Topical/systemic anti glaucoma agents to reduce IOP
• Topical steroids to reduce inflammation
• Cycloplegics to prevent from posterior synechiae
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85. Alternative treatment
Chorioretinal venous anastomosis:
• In eyes with perfused CRVO – investigators have bypassed the
occluded central retinal vein by creating a chorioretinal
anastomosis between nasal branch retinal vein and choroidal
circulation.
Tissue plasminogen activator:
• Thrombolytic agents in suspected thrombus in the central retinal
vein
• TPA converts plasminogen to plasmin which destabilize
intravascular thrombi
• Can be administered systemic, intravitreal and by
endovascular cannulation of retinal vessels
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86. Surgical treatment
Vitrectomy
• PPV may be useful to address complication of CRVO and
even to attempt to alter the natural course of the disease
Indicated:
• Non clearing vitreous hemorrhage
• Removal of epiretinal membranes and fibrovascular proliferation
if present and placement of complete endolaser PRP at the
time of PRP
• In eyes with extensive anterior segment neovascularization and
neovascular glaucoma, PPV and endolaser may be combined
with pars plana placement of a glaucoma drainage device to
avoid anterior chamber hemorrhage at the time of tube
placement
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87. • Potential role for PPV with peeling of ILM has also been
investigated for treatment of CME secondary to CRVO
Radial optic neurotomy:
• Combined with PPV with radial optic neurotomy (RON) involving
transvitreal incision of the nasal scleral ring to release pressure
on the central retinal vein at the level of scleral outlet
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88. Generalguideline for CRVO
• Treat any associated intraocular neovascularization with PRP
• Treat associated macular edema, if visually significant, with an
intra vitreal Anti VEGF or steroids
• VA loss from macular edema does not improve with grid laser
• Lower IOP if elevated
• Treat underlying medical conditions
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89. References
• Ryan’s 5th edition
• Myron yanoff 4th edition
• American academy of Ophthalmology-sec 12,
2013,2014
• Kanski’s clinical ophthalmology 8th edition
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90. CentralVeinOcclusionStudy (CVOS)
• Morethana decade
• Purpose
– To determine whether photocoagulation therapy
can help prevent iris neovascularization in eyes
withCVO andevidenceof ischemicretina.
– Toassesswhethergrid-patternphotocoagulation
therapywillreducelossof centralvisualacuitydue
tomacularedemasecondarytoCVO.
– Todevelopnewdatadescribingthecourseand
prognosisforeyeswithCVO.
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91. •
Eligibleptsweredividedin4groups:
– Group N: Eyeswithextensiveretinalischemia
(atleast10discareasof nonperfusion)were
randomlyassignedtoreceive panretinal
photocoagulationornotreatmentunlessiris
neovascularizationdeveloped.
– Group M: Eyeswithvisuallossascribable to
macularedemawererandomlyassignedto
receivegrid-patternphotocoagulationorno
treatment.
TheCentralVeinOcclusionStudyGroup: Evaluationofgridpatternphotocoagulationformacularedemaincentralvein
occlusion.The CVOS Group M Report. Ophthalmol102: 1425-1433, 1995
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92. – Group P: Eyeswith
relativelyperfused retinas
• werefollowedtoprovideinformationaboutthe natural
historyofthedisease.
• – Group I: Indeterminateeyesinwhichtheretina
couldnotbevisualizedaccuratelybecauseof
hemorrhagewerefollowedinanaturalhistory study.
TheCentralVeinOcclusionStudyGroup: Naturalhistoryandclinicalmanagementofcentralretinalveinocclusion.Arch
Ophthalmol115: 486-491, 1997.
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93. • GreenargonlaserwasusedforallTx
• Followedfor3yrswithphotographic images
• Visualacuitywasprimaryoutcomefactorin
macularedemagroup
• ClarksonJG, Central Vein Occlusion Study Group: Central vein occlusion study: Photographic protocol and early natural history. .
TransAmOphthalmolSoc92:203-215, 1994
TheCentralVeinOcclusionStudyGroup: Baselineandearlynaturalhistoryreport.ArchOphthalmol111:1087-1095, 1993.
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94. • Results
– Group M-- MacularEdema:Maculargrid
photocoagulationwaseffectiveinreducing
angiographicevidenceof macularedemabutdid
notimprovevisualacuityineyeswithreduced
visionduetomacularedemafromCVO.
– Group I-- Indeterminate:Eyeswithsuch
extensiveIntraretinalhemorrhagethatitisnot
possibletodeterminetheretinalcapillary
perfusionstatusactasif theyareischemicor
nonperfused
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