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Apr 11, 2023
RETINAL VEIN OCCLUSION
Dr. Yousaf JamalFCPS Resident
Ophthalmology UnitHayatabad Medical Complex
18/12/10
Apr 11, 2023Retinal Vein OcclusionPage 2
• Introduction of RVO• CRVO
– Demographics– Pathogenesis– Etiology– Management
• Hx, examination, investigation• Treatment
– Trials– Guidelines
• Summary / Take Home Message• MCQs
Contents
Apr 11, 2023Retinal Vein OcclusionPage 3
Introduction
• Common vascular disorder• Second common cause of blindness
after diabetic retinopathy• Cause…obstruction to venous flow• Associated risk factors….multifactorial• Classification
– Site of involvement– Extent of retinal perfusion
Apr 11, 2023Retinal Vein OcclusionPage 4
Demographics
• In Australia, prevalence of RVO…– 0.7% in pts aged 49-60 years to 4.6% in pts
older than 80 years a
• Seasonal variation found…greater than 20,000 patients in the month of January b
a Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol. Oct 1996;114(10):1243-7
b Ho JD, Tsai CY, Liou SW, et al. Seasonal variations in the occurrence of retinal vein occlusion: a five-year nationwide population-based study from Taiwan. Am J Ophthalmol. Apr 2008;145(4):722-728.
Apr 11, 2023Retinal Vein OcclusionPage 5
Common mechanism
Venous blockage
back pressure on capillaries
endothelial junction dysfunction
leakage of fluid & blood(edema / hemorrhages)
• Severe nonperfusion leads to ischemia
Apr 11, 2023Retinal Vein OcclusionPage 6
Predominant associations
• Royal college of ophthalmologists guidelines: Feb. 2009
Patient Group
Hypertension
Hyperlipidemia
Diabetes
Mellitus
No Obvious Cause
Age<50 yrs
25% 35% 03% 40%
Age>50 yrs
64% 34% 4-15% 21%
Asian 64% 50% 29% 10.7%
West Indian
83% 33% 38% 8.3%
Recurrent cases
88% 47% 3% 6%
Apr 11, 2023Retinal Vein OcclusionPage 7
Classification
• Central retinal vein occlusion (CRVO)– Non-ischemic CRVO– Ischemic CRVO
• Branch retinal vein occlusion (BRVO)– Major BRVO– Macular BRVO
• Hemicentral retinal vein occlusion (HCRVO)– Non-ischemic HCRVO– Ischemic HCRVO
Apr 11, 2023Retinal Vein OcclusionPage 8
Central retinal vein occlusion
• Painless loss of vision• Site: occlusion at or posterior to lamina
cribrosa• Two clinical types
– Ischemic CRVO (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’
• Madhusudhana KC, Newsom RS.Central retinal vein occlusion: the therapeutic options. Can J Ophthalmol.Apr 2007;42(2):193-5.
Apr 11, 2023Retinal Vein OcclusionPage 9
Demographics
• Prevalence = 0.1% a - 0.5% b
• 15-year cumulative incidence of CRVO to be 0.5% c
• NI-CRVO more common than I-CRVO• No racial predilection• Men > women• >90% CRVO occurs in > 50 yrs age
a Klein R et al. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study.Trans Am Ophthalmol Soc 2000;98:133– 41.
b Mitchell Pet al. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 1996;114:1243–7.
c Klein R et al. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. Apr 2008;126(4):513-8.
Apr 11, 2023Retinal Vein OcclusionPage 10
Pathogenesis
• Virchow triad:– Loss of vessel wall integrity– Altered blood flow– Hypercoagulable state
• Disturbance leads to thrombus formation & vessel occlusion
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• Klein & Olwin postulated:– Compression of vein by sclerotic central
retinal artery– Occlusion by primary vessel wall disease
(degenerative or inflammatory)– Hemodynamic disturbance
Klein BA, Olwin JH. A survey of the pathogenesis of retinal venous occlusion. Arch Ophthalmol 1956;56:207.
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CRVO resistance to venous flow blood stagnation & ischemiastimulates production of VEGF (vascular endothelial growth factor)
neovascularization capillary leakage
(edema)
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Etiology
• Any factor which directly or indirectly activates virchow triad….
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External compression
– Arteriosclerosis of CRA (HTN, DM, Hyperlipidemia)
– Glaucoma (5 times more likely to have CRVO)– Papilledema– Thyroid eye disease– Orbital space occupying lesions– Cavernous sinus thrombosis– Closed-Head trauma– Retrobulbar injections *
* Morgan et al. ocular complications associated with retrobulbar injections. Ophthalmology 1988;95:660.
Apr 11, 2023Retinal Vein OcclusionPage 17
Disease of vessel wall
– Systemic Vasculitis• TB• AIDS• Syphilis• SLE
– Localized inflammation• Sarcoidosis• Serpiginous choroiditis *
* Bluemenkranz et al. atypical serpiginous choroiditis. Arch ophthalmol 1773;1982:100.
Apr 11, 2023Retinal Vein OcclusionPage 18
Hematological disorders
• Clotting disorders– Activated protein C
resistance– Lupus anticoagulant
deficiency– Anticardiolipin
antibodies– Protein C & Protein S
deficiency– Antithrombin III def– Antiphospholipid
antibodies
• Nephrotic syndrome
• Paraproteinemia– Multiple myeloma– Cryoglobulinemia
• Drugs – Oral contraceptive – Diuretics
• Blood dyscrasia– Lymphoma– Leukemia– Polycythemia vera– Sickle cell disease
Apr 11, 2023Retinal Vein OcclusionPage 19
MANAGEMENT
Apr 11, 2023Retinal Vein OcclusionPage 20
History
• Symptoms– Painless loss of vision (mild to severe)– Usually unilateral
• Past & Personal Hx– HTN, DM, smoking– Hyperlipidemia – Bleeding or clotting disorders– Glaucoma– Oral contraceptive use– Head trauma / retrobulbar inj
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Examination
– VA & BCVA– Pupillary reactions– Congestion of conjunctiva or cornea– Iris…neovessels– AC angle…neovessels– IOP
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• Fundus findings– Retinal hemorrhages in 4 quadrants– Extensive hemorrhages…blood & thunder
appearance– Dilated tortuous veins– Cotton wool spots, macular edema– Optic disc
• Edema / optociliary shunts / atrophy
– Neovessels• NVD / NVE……vitreous hemorrhage
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• Diagnosing CRVO is not difficult• Main task…differentiate btw ischemic &
non-ischemic CRVO• No single criterion is helpful• Various useful tools…
– Visual acuity, pupillary reflex– Ocular neovascularization, Fundus findings– Perimetry, ERG, FFA
Apr 11, 2023Retinal Vein OcclusionPage 25
Non-Ischemic IschemicFrequency 75-80% 20-25%
VA better than 6/60 Worse than 6/60RAPD Slight or nil Marked
VF defect rare CommonFundus Less hemorrhages
& cotton wool spots
Extensive hemorrhages & cotton wool spots
FFA Good perfusion Non-perfusion > 10 DDERG Normal Reduced b-wave
amplitude, reduced b:a ratio
Prognosis 50%...6/60 or better
60%...Rubeosis & NVG
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Complications
• Principle causes of visual morbidity– Macular edema (ME)– Neovascularization (NVI>NVD>NVE) &
Neovascular glaucoma (100 days)– Vitreous hemorrhage– Optic atrophy
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Differential diagnosis
• Ocular ischemic syndrome• Diabetic retinopathy• Papilledema• Radiation retinopathy• Retinopathy due to anemia
Apr 11, 2023Retinal Vein OcclusionPage 31
Ocular Investigations
• ERG– Reduced b-wave amplitude– reduced b:a ratio– b:a ratio < 1 suggests an I-CRVO
• OCT– For macular thickness
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• Fluorescein angiography – Very useful for detecting…
• Capillary nonperfusion• Neovascularization• Macular edema
– Reliable to differentiate btw I-CRVO & NI-CRVO– >10 DD retinal nonperfusion is termed as I-
CRVO*
* The Central Vein Occlusion Study Group A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion: The Central Retinal Vein Occlusion Study Group N Report. Ophthalmology 1995;102: 1434-44.
Apr 11, 2023Retinal Vein OcclusionPage 33
– Limitations• It provides little information in early stages bcz of
extensive hemorrhages• Poor quality of angiograms• Inability to visualize peripheral retina• Interpretation is subjective & hence variable
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• FFA findings– Delayed arteriovenous transit– Macular edema – Staining along the retinal veins– Micro aneurysms, Arteriovenous collaterals– NVD, NVE– Dilated optic nerve head capillaries– Nonperfusion…hypofluorescence
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Systemic investigations
• IT IS THE RESPONSIBILITY OF THE OPHTHALMOLOGICAL TEAM TO ENSURE THAT MEDICAL INVESTIGATION AND TREATMENT IS INITIATED ON DIAGNOSIS OF RETINAL VEIN OCCLUSION.
Royal college of ophthalmologists guidelines: Feb. 2009
Apr 11, 2023Retinal Vein OcclusionPage 40
• It is the responsibility of the diagnosing physician or ophthalmologist to: – Investigate and interpret results. – Refer the patient for appropriate medical advice
with urgency according to the severity of underlying risk factor(s).
– Ensure that specialists in the relevant field should manage the rarer causes of retinal vein occlusion.
– Ensure that initiation of medical management occurs within 2 months of diagnosis
Royal college of ophthalmologists guidelines: Feb. 2009
Apr 11, 2023Retinal Vein OcclusionPage 41
Initial medical investigations
• ALL PATIENTS– FBC & ESR– Renal function tests– Random blood glucose– Lipid profile– Plasma protein
electrophoresis– Thyroid function– ECG
Royal college of ophthalmologists guidelines: Feb. 2009
• ACCORDING TO CLINICAL INDICATION– Thrombophilia screen– Anticardiolipin
antibody– CRP– Serum ACE– Autoantibodies– CXR– Fasting homocystine
levels
Apr 11, 2023Retinal Vein OcclusionPage 42
Natural history of CRVO
• NI-CRVO– Completely resolution…10% a
– ME resolves…30% in 6-15 months b
– About 50%...VA is 6/60 or worse a
– 1/3rd progress to I-CRVO in 6-12 months a
– Neovessels develop…33% in 12-15 months b
a Central Vein Occlusion Study Group. Baseline and early natural history report. Arch Ophthalmol. Aug 1993;111(8):1087-95
b McIntosh RL et al. Natural History of Central Retinal Vein Occlusion: An Evidence-Based Systematic Review. Ophthalmology 2010;117:1113–1123
Apr 11, 2023Retinal Vein OcclusionPage 43
• I-CRVO– >90%...VA is 6/60 or worse a
– ME resolves…73% in 15 months b
– NVG…>60% in 1-2 yrs a
– About 10% develop RVO in same or fellow eye in 2 yrs
• Vitreous hemorrhage…10 % of CRVO by 9 months b
a Central Vein Occlusion Study Group. Baseline and early natural history report. Arch Ophthalmol. Aug 1993;111(8):1087-95
b McIntosh RL et al. Natural History of Central Retinal Vein Occlusion: An Evidence-Based Systematic Review. Ophthalmology 2010;117:1113–1123
Apr 11, 2023Retinal Vein OcclusionPage 44
Treatment
• Systemic treatment a
– Anticoagulants…Heparin, warfarin– Fibrinolytic agents…Streptokinase, tissue
plasminogen activator– Antiplatelets…Aspirin, prostacyclin– Hemodilution
• No favorable effects on natural history b
a Mahmood T. CRVO: current management options. Pak J Ophthalmol 2009. 25(1):56-9.b Mohamed Q et al. interventions for CRVO. an evidence-based systematic review. Ophthalmology. 2007; 114:507-
19
Apr 11, 2023Retinal Vein OcclusionPage 45
• Ocular treatment– Pharmacotherapy– Photocoagulation– New techniques (Surgical)
• Certain clinical trials needs attention
Apr 11, 2023Retinal Vein OcclusionPage 46
Central Vein Occlusion Study (CVOS)
• More than a decade• Purpose
– To determine whether photocoagulation therapy can help prevent iris neovascularization in eyes with CVO and evidence of ischemic retina.
– To assess whether grid-pattern photocoagulation therapy will reduce loss of central visual acuity due to macular edema secondary to CVO.
– To develop new data describing the course and prognosis for eyes with CVO.
Apr 11, 2023Retinal Vein OcclusionPage 47
• Eligible pts were divided in 4 groups:– Group N: Eyes with extensive retinal ischemia
(at least 10 disc areas of nonperfusion) were randomly assigned to receive panretinal photocoagulation or no treatment unless iris neovascularization developed.
– Group M: Eyes with visual loss ascribable to macular edema were randomly assigned to receive grid-pattern photocoagulation or no treatment.
The Central Vein Occlusion Study Group: Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The CVOS Group M Report. Ophthalmol 102: 1425-1433, 1995
Apr 11, 2023Retinal Vein OcclusionPage 48
– Group P: Eyes with relatively perfused retinas were followed to provide information about the natural history of the disease.
– Group I: Indeterminate eyes in which the retina could not be visualized accurately because of hemorrhage were followed in a natural history study.
The Central Vein Occlusion Study Group: Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol 115: 486-491, 1997.
Apr 11, 2023Retinal Vein OcclusionPage 49
• Green argon laser was used for all Tx• Followed for 3 yrs with photographic
images• Visual acuity was primary outcome factor in
macular edema group
• Clarkson JG, Central Vein Occlusion Study Group: Central vein occlusion study: Photographic protocol and early natural history. . Trans Am Ophthalmol Soc 92: 203-215, 1994
The Central Vein Occlusion Study Group: Baseline and early natural history report. Arch Ophthalmol 111: 1087-1095, 1993.
Apr 11, 2023Retinal Vein OcclusionPage 50
• Results– Group M--Macular Edema: Macular grid
photocoagulation was effective in reducing angiographic evidence of macular edema but did not improve visual acuity in eyes with reduced vision due to macular edema from CVO.
– Group I--Indeterminate: Eyes with such extensive Intraretinal hemorrhage that it is not possible to determine the retinal capillary perfusion status act as if they are ischemic or nonperfused
Apr 11, 2023Retinal Vein OcclusionPage 51
– Group N--PRP for Ischemic CVO: Prophylactic PRP did not prevent the development of NVI in eyes with >10 disc areas of retinal capillary nonperfusion confirmed by FFA. Rather, results of this RCT demonstrate that it is safe to wait for the development of early iris neovascularization and then apply PRP
Apr 11, 2023Retinal Vein OcclusionPage 52
SCORE-CRVO study
• Standard care vs. COrticosteroids for REtinal vein occlusion study
• Funded by national eye institute in May 2003
• Multicentered RCT• 271 participants
SCORE study Report # 5. Arch Ophathalmol. 2009;127:1101.
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• Another major study which added to the armamentarium…CRUISE trial
• CRIUSE: Anti-vascular endothelial growth factor (VEGF) therapy vs. placebo in CRVO
• Rationale was…– Ischemic retina releases VEGF which leads to
ME & neovascularization
Campochiaro PA. CRUISE. Retina congress 2009.
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• In June 2010, the FDA approved a new indication for Ranibizumab intravitreal injection…for the treatment of macular edema after retinal vein occlusion.
• FDA approved Ranibizumab after CRUISE & BRAVO trials results.
http://www.medscape.com/viewarticle/724118
Apr 11, 2023Retinal Vein OcclusionPage 72
The Royal College of Ophthalmologists Guidelines
• Published in Feb. 2009.• Macular edema
– Grid laser improves the edema but no improvement in VA… so not recommended
– IVTA produce anatomical & functional improvement but effects are short lived.
– Common dose of IVTA…4mg– Repeated IVTA may not improve vision.*
* Wang L, Song H. Effects of repeated injection of intravitreal triamcinolone on macular oedema in central retinal vein occlusion. Acta Ophthalmol 2008 May 27. [Epub ahead of print] PMID: 18507724.
Apr 11, 2023Retinal Vein OcclusionPage 73
– Posurdex* in 350 or 700 g also improves vision.
– Intravitreal anti-VEGF therapy (CRIUSE) trial was going on but not published at that time.
– However, now its approved by FDA for RVO.
* Clinicaltrials.gov Identifier NCT 00485836/00486018
Apr 11, 2023Retinal Vein OcclusionPage 74
• Anterior segment neovascularization – I-CRVO should be monitored monthly for
new vessels at iris &/or angle– Pan-retinal photocoagulation is advised
when NVI or NVA are visible– If logistically not possible…2-3 months
follow-up is adequate
Apr 11, 2023Retinal Vein OcclusionPage 75
– If regular follow-up not practical…prophylactic treatment is appropriate a
– IVTA…no proven protective effect on anterior neovascularization
– Anti-VEGF can be used as an adjuvant to PRP in pts with anterior segment neovascularization secondary to I-CRVO b
a Laatikainen, L. A prospective follow-up study of panretinal photocagulation in preventing neovascular glaucoma following ischaemic central retinal vein occlusion. Graefe’s Arch Clin Exp Ophthalmol 1983; 220:236-239.
b Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina 2006; 26(3):354-6.
Apr 11, 2023Retinal Vein OcclusionPage 76
• Established neovascular glaucoma– Aim…keep eye pain free.
• Topical steroids• Atropine
– If there’s visual potential• Topical pressure lowering agents• Cycloablation
– Intravitreal and Intracameral anti-VEGF show regression of iris vessels & angle obstruction
Apr 11, 2023Retinal Vein OcclusionPage 77
Experimental treatments
– Chorio-retinal anastomosis– Radial optic neurotomy with PPV a
– Thrombolytic therapies b
• Currently…these are not recommended except as a part of clinical trials
a Arevalo JF et al ;Pan-American Collaborative Retina Study Group. Radial optic neurotomy for central retinal vein occlusion: results of the Pan-American Collaborative Retina Study Group (PACORES). Retina 2008; 28(8):1044-52.
b Murakami T et al. Role of posterior vitreous detachment induced by intravitreal tissue plasminogen activator in macular edema with central retinal vein occlusion. Retina 2007; 27(8):1031-7.
Apr 11, 2023Retinal Vein OcclusionPage 78
Recommendations for further follow-up
• Follow-up after 6 months for ischemia should be every 3 months for 1 year
• Non-ischemic eyes…every 3 months for 6 months.
• Subsequent follow-up will depend on laser Tx & complications.
• Development of disc collaterals +/- resolution of CRVO should lead to discharge from clinical supervision
SUMMARY
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Summary
• CRVO…potentially blinding• Local & systemic risk factors • Young pts need special workup • Many treatment options…difficult to
decide• Guidelines are helpful
Apr 11, 2023Retinal Vein OcclusionPage 81
Take home message
• Emphasis should be on:
– Differentiating ischemic & Nonischemic CRVO
– Exploring the risk factors (local & systemic)– Treating CRVO and Referral to physician for
risk factors– Proper follow-up
Apr 11, 2023Retinal Vein OcclusionPage 82
THANKS
Apr 11, 2023Retinal Vein OcclusionPage 83
MCQs1. A 69-year-old man presents with sudden onset of painless,
DV in right eye of 1 week's duration. BCVA was 20/200 OD and 20/25 OS with no afferent pupillary defect OD. He is diagnosed as CRVO case with diffuse macular edema. FA reveals retinal capillary non-perfusion in less than 10 disc areas and diffuse dye leakage in the fovea. OCT shows large cystic spaces with an increased foveal thickness of 495 μm.
Based on the results of SCORE-CRVO trial, which of the following would be the best option for this patient?
1. Intravitreal injection(s) of 1 mg triamcinolone2. Intravitreal injection(s) of 4 mg triamcinolone3. Intravitreal injection(s) of either 1 mg or 4 mg triamcinolone4. Observation
Apr 11, 2023Retinal Vein OcclusionPage 84
• Ans. 1
Apr 11, 2023Retinal Vein OcclusionPage 85
…Continued case 1…
• How would treatment differ if the patient is treated according to the CRUISE trial?
1. Observation2. Single grid macular laser treatment3. Monthly intravitreal injections of an anti-VEGF agent4. Monthly intravitreal injections of a corticosteroid
Ans. 3
Apr 11, 2023Retinal Vein OcclusionPage 86
…Continued case 1…
• The treating physician opts for intravitreal injection of an anti-VEGF agent.
Assuming an optimal response, what kind of improvement would the average patient expect if treated by monthly intravitreal ranibizumab for 6 months?
1. 1-line gain2. 2-line gain3. 3-line gain4. 4-line gain
Ans. 3
Apr 11, 2023Retinal Vein OcclusionPage 87
…Continued case 1…
• In fact, in this case, vision in the right eye improves from 20/200 to 20/80 at 1 month. FT improves from 495 to 360 µm. There is no noted neovascularization.
Which of the following should be considered if the treating physician follows the CRUISE trial protocol?
1. Observation2. Intravitreal injection of an anti-VEGF agent and
intravitreal injection of a corticosteroid3. Second injection of intravitreal anti-VEGF agent only4. Intravitreal injection of a corticosteroid only5. Macular grid laser
Apr 11, 2023Retinal Vein OcclusionPage 88
Ans. 3
Apr 11, 2023Retinal Vein OcclusionPage 89
…Continued case 1…
• If the same pt is to be treated by following CVOS protocol then what would be the be the Tx
1. Prophylactic PRP2. Macular grid laser3. IVTA4. Observation
Ans. 4
Apr 11, 2023Retinal Vein OcclusionPage 90
…Continued case 1…
• If this pt later develops I-CRVO & have macular edema but no signs of neovascularization. What would be the best option while following CVOS protocol.
1. Immediate PRP2. PRP on next visit3. Macular grid4. IVTA5. Observation
Ans. 5
Apr 11, 2023Retinal Vein OcclusionPage 91
MCQ 2
• Features that may help distinguish CRVO from carotid artery occlusive disease include all of the following except
1. Dilated retinal veins2. Tortuosity of retinal veins3. Retinal artery pressure4. Ophthalmodynamometry
Ans. 1
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MCQ 3
• The most common risk factor for CRVO is1. Diabetes2. Hypertension3. Hyperlipidemia4. Smoking5. Glaucoma
Ans. 2
Apr 11, 2023Retinal Vein OcclusionPage 93
True/false
• Following are true about CRVO1. Hematological disorders are more common in pts <60
yrs age than those above 60 yrs2. Prognosis for younger pt is better than for older pts3. CVOS shows aspirin can prevent recurrence in
affected or involvement of fellow eye4. CVOS show clear benefit of prophylactic laser Tx in
ischemic eyes5. Macular grid laser is useful in presence of ME with VA
6/18
Ans. T, T, F, F, F
Apr 11, 2023Retinal Vein OcclusionPage 94
True/false
• The following conditions may cause central retinal vein occlusion in a young patient:
1. protein C deficiency2. excess protein S3. Antithrombin III deficiency4. atrial fibrillation5. factor V Leiden mutation
Ans. T,F,T,F,T
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Next
• Lecture– Dr. Yousaf Jamal
• Retinal vein occlusion…continued
• Journal club– Dr. Iqbal