- Intravitreal triamcinolone (IVT)
- Osardex (intravitreal seroid implant)
- Anti-VEGF drugs...Avastin/lucentis..patients
- A mild then later a much more severe central retinal vein occlusion
- CSME = clinically significant macular oedema.
Retinal vein occlusion: notes for professionals
For older patients
- 20% RVO recur if cause not addressed
- blood pressure <140/80 in clinic
- FBC, ESR or CRP, lipids, U & Es, Creatinine, eGFR, HbA1c, TSH
- an ECG will identify a large heart....this would need treatment to lower blood pressure
- homocysteine, atherosclerotic and thrombophilic. For an accurate homocysteine level, send sample straight to lab, include b12 and folate. If the result if still elevated the patient needs folic acid and other cvs risk factors addresing.
- ? obstructive sleep apnea Arch 2010
- Polycythaemia...need HCT < 45% NEJM 2013
- ( HTMHFR homozygous O14)
- lupus anticoagulant
- Retina 19 ".. test for antithrombin III activity; activated partial thromboplastin time; fibrinogen; protein C activity; protein C antigen; protein S (total & free); plasminogen activity; Factor V Leiden, lupus anticoagulant, homocysteine levels, and cryoglobulins.
- Additional targeted workup was based on a case-by-case basis such as neurovascular imaging or uveitis workup. A similar hypercoagulable workup was performed for two patients (both in their early 50s at presentation) and was unrevealing. Of the 36 younger patients with CRVO, 10 had a negative workup and five had either no documented workup or were lost to follow-up. Of note, 10 of these 15 patients without identified nontraditional risk factors did have the traditional risk factors of hypertension, diabetes, hyperlipidemia, smoking, and/or glaucoma. The following nontraditional risk factors were identified in the remaining 21 patients. Four women were either on hormonal oral contraceptives or had a hormone-secreting intrauterine device, whereas two additional women developed CRVO in the immediate postpartum period. A review of the workup of all younger patients revealed that one patient had an incomplete carotid artery occlusion, whereas another had complete vertebral artery occlusion. Two patients were diagnosed with a coagulopathy, one of whom had a methylenetetrahydrofolate reductase mutation that increases homocysteine levels, and one with a nonspecific coagulopathy reported by the primary care physician. Two patients were identified during workup to be heterozygous for Factor V Leiden. Two patients regularly engaged in very intense exercise and had a CRVO onset shortly after such exercise, one of whom developed a subsequent CRVO in the fellow eye approximately 1 year later with workup negative while still exercising heavily. Diagnoses identified in only one patient each include sarcoidosis, systemic lupus erythematosus, undifferentiated connective tissue disorder, autoimmune hepatitis, and Behçet disease. In addition, one patient with cystic fibrosis developed CRVO shortly after cardiac catheterization, and another developed CRVO while on sorafenib (tyrosine kinase inhibitor) for bronchiolitis obliterans."
- add thrombophilia screen, especially if patient has had other venous-thromboembolic disease
- this includes factor V leiden, antithrombin 111, protein C & S
- BP, lipids, increased body mass Retina 2010
- lupus anticoagulant and antiphospholipid antibody
- Retina 2011
- thrombophilia unlikely Retina15
- JAMA 18 A new treatment not readily available
- older patients have more ischaemic eyes and are more likely to need laser
- eyes at risk
- afferent pupil defect
- vision 6/36-6/60 or worse
- lots of retinal ischaemia
- those with deteriorating vision..this indicates increasing ischaemia see
- BRVO very unlikely to develop rubeosis, CRVO much more
(hemispherical RVO in between)
- older patients > 30 disc areas of ischaemia
- treat risk factors as above to protect the other eye etc
- laser 3000 burns 0.02 seconds x 3+ sessions or so if significant ischaemia
(argon laser...heavier burns than diabetes settings)
- where time allows (seldom in the UK) review each month to laser when rubeosis evident (iris or angle). This is controversial...about 50% of ophthalmologists like to laser before rubeosis, including DK, that is lasering all severely ischaemic eyes.
- consider indirect laser
- CRVO: some patients will need laser for NVD and NVE, not just NVG. Patients with BRVO and hemispherical RVO may need grid laser for CSME especially if oedema substantial, but there is little prospect of improving sight. This is on the basis that increasing/severe CSME may cause even more visual loss.
- to detect eyes whish may become rubeotic examine the minor arterial circle of the iris with the slit lamp, see
- look for peripheral ischaemia Retina 2011; risk of rubeosis Retina 2012
If available and there is considerable CSME, anti-VEGF will be more effective.
My current technique (modified from PubMed)
- area centralis lens, reasonably high magnification
- 50 µ
- 0.01 seconds
- grid pattern...laser...2 spaces ...burn
- ~80 mw, more if there is oedema (~130mw)
- first 2 laser sessions no FFA
- if oedema remains, anti-VEGF
- if CSME recent, consider IVT or IVA
- these are the same settings used for a macular grid for diabetes
Always laser more than 1 disc diameter from the fovea, further away if the surgeon is inexperienced or the patient is moving.
Laser in green, slow repeat, move away from fovea with small subthreshold burns. If the burn is visible, turn the power a little lower. Laser between vessels as shown. If there is no vessel, 'imagine' one, as a line between 2 two landmarks. The strategy is aimed at avoiding the fovea at all costs. Always know where you are. Anti-VEGF more effective.
- If there is lots of retinal ischaemia, retinal new vessels can develop
- this can follow a severe branch retinal occlusion
- more likely to follow a central retinal vein occlusion..the more severer forms
- if the new vessels grow they are likely to bleed and then cause a retinal detachment
- I would prefer to laser to prevent these....any eye with lots of retinal ischaemia
- use the PRP settings as for diabetes as here
- small burns cause less field defect
- Subthreshold laser may help BJO 2011
Rubeosis really needs combination treatment
- Anti-VEGF injection to stop the rubeosis (and this may need to be repeated [regular treatment is not needed]) Anti-VEGF is probably first choice treatment for rubeotic glaucoma, if available
- cyclodiode laser to lower the pressure (and this may need to be repeated)
- Once the pressure is down and the retinal view clear, PRP argon laser.
- 1500-2000mw, 1500-2000ms, higher settings for NVG than in a seeing eye
- good peribulbar anaesthesia....this is very painful without
- 40 spots, 10 each quadrant, clean plate first, try to avoid pops
- test laser first on black paper as laser 'wire' fibres become damaged and power can drop off
- transilluminate for ciliary processes (especially young patients and myopes)
- after laser, maxidex qid, atropine 1% bd, also ibuprofen 600mg bd
(note contraindications to ibuprofen), stop anti-glaucoma therapy
- see 2-3 weeks
- retreat if necessary. (In practice only very few patients need 3 treatments, and none more.)
- aim of treatment is to keep a comfortable eye, not really to treat the pressure
- laser of the ischaemic none-perfused retina (when the eye is treated with anti-VEGF injections) is not needed Retina 2013
If your clinic is getting a lot of patients with NVG, increase prevention such as treating risk factors and more laser as above. There is a lot of controversy in the timing of laser in severe CRVO. Some people laser more (and think they prevent more NVG) others laser less (and think they get no more NVG).
Treat incipient RVO actively to prevent progression, lower eye pressure if borderline
The other eye may be at risk Retina15
See This can be identified by FFA features:
- delayed and patchy filling
- venous tortusosity and beading
- mid-peripheral blot haemorrhages
- more often bilateral, one eye may have good vision
Incidence is 2/1000 over 5 years. Risk factors include
- blood pressure
- abnormalities of FBC, ESR or viscosity , total protein, immunoglobulins, fasting blood sugar
- smoking (controversial)
- Dodson reports a direct relationship between RVO and platelet glycoprotein genetic differences. This is in the GpIa/IIa complex, which initiates platelet adhesion at the start of a thrombosis. Strangely, it is not related to DVTs. It seems to synergistically with other factors.
- high homocysteine and here Many patients have high homocysteine levels. There may be a genetic cause of this, but levels can be lowered (and vascular occlusions generally be prevented) by a healthy diet with 9 (men) 7 (women) portions of vegetables/fruit/day. See how to lower levels.
- factor 12 deficiency
- other genes see
- Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study : age, blood pressure, and obesity are related.
- 15 year study, Klein . Analysis suggest migraine increases risk of branch rvo, diabetes central, and so on. The burden of RVO Eye 11
- Prevalence/associations India Retina 2013
For younger patients
- the 'pill', which should be stopped
- HRT, which should be stopped
- Protein C or S abnormalities (anticoagulants needed), factor V leiden
- APL syndrome (antiphospholipid antibody) (need anticoagulation)
- ask about mouth ulcers...if present and recurrent consider Behcets
- genetic differences as above
- shorter eyes are also linked to RVO's short axial length
- artery & vein are in close contact, in the optic nerve or in a sheath in the retina
- artery presses on vein
- endothelium is damaged also (a separate mechanism)
- thrombin forms
- thrombin & occlusion extends
- inflammation in vessel wall
- angiogenesis of occluded vessel
- (vein bursts and retinal haemorrhages evident)
- multiple vascular channels develop
- microaneurysms develop
- vein re-canalises, but retina damaged around
- healthy cells produce HIF (hypoxic inducing factor), but this is rapidly broken down
- in hypoxia, it is not broken down, and stimulates cells to make VEGF
- Studies confirm the concentration of AC VEGF is directly proportional to the risk of rubeosis.
- serous detachments..look for peripharal abnormalities Retina 12
- inflammation after the rvo JAMA 13
- collaterals are not related to better visual outcome Retina 14
We have nearly stopped using this treatment and prefer intravitreal steroid implants, Avastin & laser, see. IVT was considered as a new treatment for the macular oedema that occurs with retinal vein occlusion, see. IVT may improve the sight, but the effect may not last long. There are risks, see , 10% patients developed severe glaucoma.
- Complications are discussed here, but the standard dose is 2mg
- A recent paper suggests the IVT is best given early for best results (Oh 07)
- Cheng 2009: triamcinolone no benefit versus Avastin and more adverse events
- Moschos...benefit is temporary
- For branch retinal vein occlusions this SCORE report suggests 1mg intravitreal triamcinolone & grid laser is no more effective than grid laser alone, but the 1 mg dose was safer than the 4 mg dose. Laser is best, Score 6
- For central retinal vein occlusions in this SCORE report IVT repeated at regular intervals, improves vision by 25%
- For central rvo, comparing IVT to IVA (triamcinolone to Avastin) IVT reduces oedema more but causes more side effects (glaucoma) Tao 2010
- does not influence shunt vessels Retina 2013
- These are now our standard treatment for an ischaemic RVOs
- These can be helpful intravitreal steroid implants.
- branch and central RVO Oph 2011
- Osardex and Avastin Retina 2012
- Branch retinal vein occlusion, it helps, not for CRVO Eye 2013
- Anti-VEGF probably best for mild occlusions
- see. We would certainly prefer intravitreal steroid implants or less so IVT.
Anti-VEGF in RVO
- inject as needed Ophth 14; Eylea Eye16
- now standard treatment
- start early...much more effective
- wil need retreatment
- PRP laser also if lots of retinal ischaemia
- stop treatment if poor response
- treatment plan Eye 16 , here modified here considerably
|Complete responder||fluid on oct|
|partial response||poor response|
? extend interval between injections
|consider PRP laser; look for ischaemic areas clinically or with FFA|
- also sector PRP laser also if lots of retinal ischaemia
- stop treatment if poor response
Case 1 (cases presented at Congress) bus driver
- 57 y bus driver
- hand movements..svere CRVO, very ischaemic
- anti-VEGF and and PRP laser..but will not get enough sight back to drive bus
- afro-carribean, hyertensive, diabetes, longstanding macular oedema from retinal vein occlusion, no response to anti-VEGF
- brvo, cmo, osardex, vision improved, repeated osardex, cataract, phaco, removed, CMO still, prp sector, do you continue osardex?
- 66y patient,, small brvo, cmo, lucentis reduced oedema, stayded dry, patient discharged or virtual clinic?
- severe cme, dry with lucentis, recurred, patient had MI
- patient pregnant, no injections, new vessels developed, had PRP laser, delived baby, then avastin
Notes about anti-VEGF
- Very helpful. Osardex probably preferable if there is a lot of ischaemia
- branch retinal vein occlusion (BRAVO) , but has to be given repeatedly. PACRSG 2009
- central retinal vein occlusion (CRUISE). Avastin helps in CRVO Retina 2011(central).
- BJO 2011 Lucentis helps
- VEGF trap BJO 2013
- AJO 14 anti-VEGF versus laser brvo
This situation is not uncommon: a patient presents with reasonable vision and and central rvo with haemorrhages. But 4 months later, the sight becomes much worse and the haemorrhages (and ischaemia) increases (laser etc is needed).
Recent suggestions indicate such a patient might have had a second vein occlusion. Such a patient illustrated here. We cannot explain the 'second' occlusion; the high viscosity (ESR) may be relevant.
CF vision; lots of haemorrhages, more macular oedema
6/12 vision, scattered retinal haemorrhages
|Male, 86y, minor rvo July. in November much worse. BP ok, high CRP & ESR (ESR 35) enlarge|