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Pathogenesis, Risk Factors, Investigations and Management of Retinal Vein Occlusion (RVO
- 1. (RVO)
- 2. PATHOGENESIS • Age related local and systemic factors • BRVO • Arteriosclerotic thickening of branch retinal artery, compresses the venule at crossing points (shares common adventitia) • Endothelial loss, turbulent flow, thrombus formation • CRVO • Thrombosis of CRV at or posterior to the lamina cribrosa • Atherosclerotic changes in central retinal artery, compressing the vein at crossing points (common sheath) Venous occlusion >> Elevated venous and capillary pressure >> Stagnation of flow >> Retinal hypoxia >> Damage to capillary endothelium >> Extravasation of blood >> Liberation of VEGF
- 3. RISK FACTORS • Age • >50% cases are >65 yrs • Hypertension • In 70% of RVO over 50 years • In 25% of younger • Most prevalent in BRVO • Hyperlipidaemia • In 33% (any age) • DM • In 15% over 50 years • More in Asia, Blacks • Uncommon in young • Glaucoma / OHT • Higher risk of CRVO (x5.3)/ BRVO (x2.5) – (EDCC) • Hypercoagulabilty • OCP • Shouldn’t be taken after RVO • Smoking • ?? Not proven • Dehydration • Myeloproliferative disorders • Myeloma, polycythemia • Thrombophilia • Hyperhomocysteinaemia • Antiphosholipid Xd • Factor V Leiden mutation • Inflammation • Behcet, Sarcoidosis, Wegner • Orbital disease • Renal failure • SLE • Carotid occlusive disease • Sleep apnoea
- 4. BRVO CRVO Age Age HTN HTN Smoking Open angle glaucoma Glaucoma DM Hypercoagulable state Hyperlipidaemia Hypercoagulability
- 5. ROUTINE INVESTIGATIONS • Blood pressure • ESR • FBC • Random / Fasting glucose • Lipid profile • Plasma protein electrophoresis • Multiple myeloma • BU, SE, S.Cr • Thyroid function tests • ECG
- 6. Selected Investigations • In patients with… • Under 50 years • Bilateral RVO • Previous thrombosis • Common Ix negative • CXR • Sarcoidosis • TB • Left ventricular hypertrophy (HTN) • CRP • Plasma homocysteine (hyper) • Thrombophilia screening • Thrombine time • Prothrombin time • APPT • Protein C, S • Factor V Leiden mutation • Lupus anticoagulant • Anticardiolipin antibody • Autoantibodies • Rheumatoid factor • ANA • Ds-DNA • ANCA • ACE levels • VDRL • Carotid duplex
- 8. SYMPTOMS • If central macula involved – painless blurred vision and metamorphopsia • Visual acuity • Variable • 50% untreated eyes retain 6/12 or better • 25% 6/60 or worse • Causes of visual decline: • Macular oedema (90%) • Macular ischaemia • Haemorrhage over fovea • Vitreous haemorrhage (4%) • ERM/ VMT • Serous RD (20%) • TRD, RRD, TRD+RRD
- 9. Examination • NVI/ NVG • Less common (2% at 3 years) than CRVO • Dilatation and tortuosity of affected venous segment, flame shaped/ dot-blot hemorrhages • ST BRVO most common (63%) • Site of occlusion at arteriovenous crossing point • Acute features resolve within 6 – 12 months • Venous sheathing, sclerosis • Collateral vessels • Near areas of capillary non perfusion after weeks-months • Poorly functioning to normal VEIN • Tortuous / looping channels • May cross the horizontal raphe (sup and inf arcades) • Better prognosis • Ablation should be avoided in laser
- 10. • Retinal neovascularization • In 8% by 3 years • Risk high if > 5 disc area of non perfusion (33%) • NVD << NVE (2x risk) • Typically within 6-12 months • Long term visual loss is due to, • Cystoid macular oedema • Hard exudates • Pigmentary maculopathy • Subretinal fibrosis • Epiretinal membrane • Recurrent VH, Tractional RD, RRD – rare
- 11. • Branch Vein Occlusion Study (BVOS) • Incidence of NVE/ NVD was 36% in eyes with extensive retinal ischaemia (at least 5 disc D) • Vitreous haemorrhages in 60 – 90% if laser photocoagulation was not performed Risk of RVO (CRVO/BRVO) in the fellow eye is 10% in 3 years
- 12. INVESTIGATIONS • FFA • Peripheral / macula ischaemia • Capillary non perfusion • Staining of vessel walls • Vessel ‘pruning’ (small branches failing to fill) • Haemorrhage • Oedema • Collateral vessels • Delayed venous filling • OCT • Quantifies macula oedema
- 13. MANAGEMENT • Systemic assessment and referrals • Observation • If VA 6/9 or better • FFA • At 3 months (allows bleeding to settle) • If VA 6/12 or worse • May not be required now with AntiVEGF • In dubious NV • Sector PRP • In NVE or NVD (some wait for VH) • Can be combined with anti-VEGF 4 weekly • Urgent in NVI • Intravitreal anti-VEGF • For macular oedema
- 14. • Intravitreal dexamethasone implant • Can be repeated after 4-6 months • A/E- cataract, glaucoma • Alone or with laser • Intravitreal triamcinolone • As effective as laser for ME • Periocular steroids – less effective • Macular laser • If VA is 6/12 or worse after 6 months, due to ME • Now as an adjunct to anti-VEGF • Micropulse laser – onset of action slower • Review • If no intervention – 3 months >> 6 months >> upto 2 years • To detect neovasculariation
- 15. • Branch Vein Occlusion Study (BVOS) • Laser treatment for macular oedema is more likely to have 20/40 or better VA in 3 years (60% vs 34%) • Scatter photocoagulaltion to the non perfused retina reduced the risk of VH from 60% to 30% • Ischaemia alone was not an indication for treatment provided proper follow up • BRAVO • 0.5/ 0.3mg IV Ranibizumab monthly vs sham • VA – 3 line gain in 60% vs sham (30%) in 6 months • HORIZON – VA maintained thereafter with reduced inj. nos • VIBRANT • Aflibercept (VEGF-Trap) had similar results • CRAVE • No difference between all 3 ant-VEGF agents • SCORE • IV Triamcinolone comparable with macular grid laser • More likely to develop cataract / high IOP
- 16. • BERVOLT • Retrospective Bevaciumab study for both BRVO/ CRVO • Bevacizumab is an alternative to other anti-VEGF • RELATE • No short term clinically significant benefit between 2mg vs 0.5mg Ranibizumab • BRIGHTER • Ranibizumab with or without laser is better than laser alone • GENEVA • Both CRVO/ BRVO • Dexamethasone (0.7mg) implant vs sham • CDVA better at 3 months but no difference at 6 months
- 17. TREATMENT ALGORITHM 1. SYSTEMIC RISK FACTORS 2. OPHTHALMIC MANAGEMENT • BASELINE • VA better than 6/12 – observe for 3 months • VA 6/12 or worse + ME + Haemorrhages not masking fovea • FFA – foveal intergrity • No macular ischaemia – observe for 3 months • Mild – moderate macular ischaemia – Ranibizumab/ Ozurdex • Severe macular ischaemia – observe for NV • VA 6/12 or worse + ME + haemorrhages masking macula • Monthly Ranibizumab for 3 months/ Ozurdex • FFA at 3 months • If severe macular ischaemia – no treatment beneficial
- 18. • AT 3 MONTHS FOLLOW UP • Consider modified grid laser if persistent ME, no/ minimal macular ischaemia • VA 6/9 or better – observe or continue antiVEGF/ Ozurdex (see CRVO) • FURTHER FOLLOW UP • 3 monthly intervals for 18 months • If recurrence consider reinitiating treatment • IF NV • Sector PRP +/- IVB • Follow up 3 monthly until 2 years
- 19. DDs OF BRVO • Hypertensive retinopathy • Diabetic retinopathy • Radiation retinopathy • Macular telangiectasia • RAP • ARMD • Ocular contusion/ retinal trauma
- 21. IMPENDING (PARTIAL) CRVO • In younger patients • Prognosis is usually good • A proportion will deteriorate to ischaemic CRVO • Transient blurring of vision worse on waking • Mild retinal venous dilatation and tortuosity, few dot/blot haemorrrhages • Mild macular oedema • Rx – not established • Correcting predisposing systemic conditions • Avoiding dehydration • Lowering IOP
- 22. NON ISCHAEMIC CRVO • More common than ischaemic • 1/3rd develop ischaemic CRVO within months • CVOS - 16% in 4 months; 34% in 3 years • Sudden painless monocular fall in vision • VA variable (6/36 – 6/60) • If not ischaemic vision recovers to near normal in 50% • No/ Mild RAPD • Fundal signs in all 4 quadrants • Macula and disc oedema common but mild • Perivenular (patchy) ischaemic retinal whitening (PIRW) – an early sign
- 23. • Mild visual field changes • Acute signs resolves over 6 – 12 months • Later findings • Venous tortuosity, telangiectasia, microaneurysms • Sheathing and sclerosis • Epiretinal gliosis • Macular pigmentary and atrophic changes • Peripheral and optic disc collaterals • Main cause of poor vision – chronic macular oedema / secondary atrophy Disc collaterals – markedly decreased risk of NV
- 24. • FAF • In acute RVO – fern like perivenular hypoautofluorescence (masking by oedema) • Corresponds to PIRW • FFA • Delayed AV transit time • Masking by haemorrhage • Good capillary perfusion (minimal areas of non perfusion) • Late leakage • OCT – for macular oedema
- 25. ISCHAEMIC CRVO • Visual morbidity mainly due to • Macular ischaemia • NVG • Sudden and severe monocular painless visual impairment • VA usually CF or worse • RAPD present • NVI in 50% - usually in 3 months (100 day glaucoma) • Gonioscopy – angle neovascularization
- 26. • Severe tortuosity and engorgement of all branches • CWS prominent • Optic disc swelling and hyperaemia • Acute signs resolve in 9-12 months • Later signs • Atrophic retinal and RPE changes • RPE hyperplasia • ERM • Chronic CMO • Subretinal fibrosis (rare) • Retinal NV – 5% (less common than BRVO) • Optic disc collaterals common
- 27. • FFA • Marked delay in arteriovenous transit time • Masking by retinal haemorrhage • Capillary non perfusion • Vessel wall staining and leaking • >10 disc D non perfusion – risk of NV • OCT – quantifies CMO • ERG – depressed
- 28. Features of i-CRVO 1. BCVA – CF or less (<6/60) 2. RAPD 3. VF – dense central scotoma + peripheral constriction 4. Fundus • Marked venous dilatation • Extensive 4 – Q haemorrhages • Retina oedema • Numerous CWS 5. FFA - >10 disc D of non perfusion 6. ERG – b:a amplitude ration is decreased
- 29. HEMIRETINAL VEIN OCCLUSION • ?variant of CRVO • Cacn be ischaemic/ non ischaemic • Less common • Extensive retinal ischaemia leads to NVI • Mx as CRVO • Macular oedema • Mx as BRVO • Altitudinal visual field defect • NVI commoner than BRVO, less than CRVO • NVD common than CRVO/ BRVO
- 30. MANAGEMENT • Systemic assessment • Macula oedema • If VA < 6/9 or significant central thickening (>250um) • Unlikely to benefit if 6/120 or worse • Intravitreal anti-VEGF • Monthly for 6 months • 2-3 line gain • Intravitreal dexamethasone implant (GENEVA) • Can be repeated in 6 months • Good outcome if within 90 days of CMO • Intravitreal triamcinolone (SCORE) • Laser photocoagulation • No visual benefit (except in young ??) • New – chrioretinal anastomosis, vitrectomy + radical optic neurotomy, local rtPA infusion
- 31. • Neovascularization • Urgent PRP in NVI / NVA • Intravitreal anti-VEGF every 6 weeks (as an adjunct) • Mx of NVG… • VH – vitrectomy and endolaser • Review • Ischaemic – monthly x 6months >>> 2 years • Non ischaemic – initially after 3 months > SOS > 2 years • Need gonioscopy each visit Risk of CRVO in the fellow eye is 1% per year
- 32. • Central Vein Occlusion Study (CVOS) • Grid pattern laser for macular oedema does NOT improve VA; not recommended • Prophylactic PRP did not result in statistically significant decrease in iris neovascularization • PRP performed at the first sign of NVI • CRUISE • 0.5/ 0.3mg IV Ranibizumab monthly vs sham • VA – 3 line gain in 50% vs sham (15%) in 6 months • COPERNICUS / GALILEO • Aflibercept (VEGF-Trap) had similar results • SCORE 2 • Bevacizumab non inferior to Aflibercept • CRAVE • No difference between all 3 ant-VEGF agents
- 33. • SCORE • IV Triamcinolone better than observation • More likely to develop cataract / high IOP • GENEVA • Both CRVO/ BRVO • Dexamethasone (0.7mg) implant vs sham • CDVA better at 3 months but no difference at 6 months • COMRADE • Dexamethasone (0.7mg) implant vs monthly Ranibizumab • At 3 months efficacy similar • At 6 months ranibizumab better
- 34. Systemic management • Control of risk factors • Avoid smoking • Antiplatelet therapy – not prescribed unless systemically indicated (not recommended) • Hormone replacement – controversial • OCP – should be discontinued • Avoid dehydration
- 35. TREATMENT ALGORITHM RCOPHTH 1. SYSTEMIC MANAGEMENT 2. OPHTHALMIC MANAGEMENT • BASELINE • BCVA • Colour fundus photography • Fluorescein angiography – for ischaemia • OCT – for macular oedema • IOP • Gonioscopy – for NVA
- 36. • NO NV WITH MACULA OEDEMA • VA 6/96 or better – antiVEGF or Ozurdex • VA less than 6/96 – can offer Rx; should watch for NV • VA better than 6/12 – can observe +/- • Ranibizumab / Aflbercept – in young/ Hx of glaucoma • Monthly until maximum VA (stable for 3 months) • Cessation if no response after 6 injections • Ozurdex – in recent cardiovascular events • Retreatment 4 – 6 monthly • Can switch agents if no response (no trials!) • At followup – (monthly) • VA, macular thickness, IOP, NVA/NVI
- 37. • NVA/ NVI WITH OPEN ANGLES • Urgent PRP • R/v at 2 weeks • PRP + IVB if NVA/ NVI persist • NVA/ NVI WITH CLOSED ANGLES AND HIGH IOP • Urgent PRP + cyclodiode/ tube shunt surgery • If IOP normalises can consider IVB • If IOP high – add topical and medical Rx Prophylactic laser in i-CRVO with no NV considered in poor followup patients Guarded prognosis should be explained
- 38. DDs of CRVO • Hyperviscosity retinopathy • Bilateral • Usually related to dysproteinemia (Waldenstom macroglobulinaemia, multiple myeloma, blood dyscrasias - polycythemia) • Ix - FBC, protein electrophoresis, blood viscosity • Ocular ischaemic syndrome • Haemorrhages are limited to the deeper layers • Absent vascular tortuosity Causes of TOTUOSITY • Congenital • Hyperviscosity • Anaemic • Hypertensive
- 39. Clinical Sign OIS CRVO Diabetic Retinopathy Retinal Veins Dilated but not tortuous Dilated and tortuous Dilated and beaded Age 50's to 80's Variable 50's to 80's Hemorrhages (location) dot and blot (mid- periphery) and in deeper retinal layers Flame shaped (all quadrants) in nerve fiber layer Dot and blot (posterior pole and mid- periphery) Microaneurysms (Location) Common (mid-periphery) Uncommon Common (Posterior pole) Other Microvascular abnormalities Macular telangectasias, retina AV communications, capillary dropout opto-ciliary shunts, capillary dropouts intraretinal microvascular abnormalities, capillary dropout Hard exudates No Rare Common Optic Disc Normal Edema (common) Rarely diabetic papillopathy Central retinal artery perfusion pressure Decreased Normal Normal Fluorescein Angiography A-V transit time Prolonged Prolonged Usually normal Retinal Vessel Staining Arteries>Veins Veins>Arteries Usually absent Macular edema Rare Common Common Choroidal filling Delayed, patchy Normal Usually normal Microaneurysm mid peripheral usually at posterior pole usually at posterior pole Optic disc hyperfluorescence may be present Usually present absent except papillopathy or new vessels at the disc or optic neuropathy
- 40. PAPILLOPHLEBITIS • Poorly defined condition • Affects individuals under the age of 50 years • May have HTN and DM • May be a variant of CRVO • Diagnostic overlap with diabetic papillopathy • Mild - moderate visual loss • No RAPD • Good prognosis • Disc oedema + haemorrhages +/- CMO • Maybe bilateral – have to exclude raised ICP • Investigate as for young CRVO • Rx – antiVEGF/ steroids