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1. CENTRAL RETINAL VEIN OCCLUSION
BY- DR.HARSHIKA

2. INTRODUCTION
• Retinal vein occlusions
RVOs ( BRVO+CRVO+HEMI-
CRVO) are 2nd most
common retinal vascular
diseases ( 1st is Diabetic
Retinopathy )
• Branch retinal vein
occlusions(BRVO) > CRVOs
• BRVO-80%, CRVO-20%

3. CRVO RISK FACTORS
CRVO is multifactorial in origin,in which
Virchow’s traid of abnormalities of
blood flow
vessel walls
blood coagulability
all play a role

4. CRVO SYSTEMIC RISK FACTORS
a) Age- Higher age. 90% of CRVOS are > 50 years old
b) Hypertension- present in 64% of patients with RVO
c) Diabetes Mellitus- present in 10-25% of RVO cases
d) Obesity
e) Cardiovascular diseases
f) Hyperlipidemia -35% cases – cholesterol >6.5 mmol/l

5. • g) Inflammatory Diseases- they cause retinal vasculitis (pts aged < 45 yrs)
• ENDOTHELIAL DAMAGE
• Sarcoidosis
• Behcet’s disease
• Wegener’s granulomatosis
• Goodpastures syndrome
• Other diseases with retinal vasculitis

6. • H) Myeloproliferative disorders ( to be considered in pts < 45 yrs )-
• STASIS OF BLOOD FLOW
• Polycythemia
• Abnormal plasma proteins ( myeloma,waldenstrom macroglobuinaemia )
• Leukemias
• Thrombophilic disorders ( to be considered in pts < 45 yrs)-
• HYPERCOAGULABILITY
• Hyperhomocysteinaemia
• Anti-phospholipid antibody syndrome ( lupus anticoagulant & anti-cardiolipin )

7. • J) Inherited disorders of hypercoagulability
• Factor V Leidin deficiency
• Protein C deficiency
• Protein S deficiency
• k) More unusual associations
• Oral contraceptives
• Chronic renal failure
• Other secondary causes of HTN and DM (e.g.- CUSHINGs SYNDROME)
• Secondary causes of hyperlipidaemia (e.g.- hypothyroidism)

8. CRVO OCULAR RISK FACTORS
a) Glaucoma – CRVO>BRVO ( 5times more likely to have CRVO if glaucoma is present )
b) Retinal vasculitis – Eales disease
c) Carotid cavernous fistula
d) Orbital tumors
e) Disc drusens

9. Ocular risk
factors
Eale’s
disease

10. Carotid
cavernous
fistula

11. RISK FACTORS FOR RVO

12. SITE
• The occlusion of the CRV occurs
at the level of lamina cribrosa or
just behind
• The occlusion occurs due to
formation of a thrombus in the
vein

13. Why at lamina cribrosa?-conditions that
favor occlusion at this place
Narrow lumen of CRV and CRA
in lamina cribrosa-tunnel in LC is
narrow
Common adventitial sheath
envelopes CRA and CRV in lamina
cribrosa. So an atherosclerotic
CRA can compress CRV and cause
turbulence of flow-thrombus
formation if other risk factors
play a part too

14. Green et al Pathogenesis
• Blood flow is turbulent in CRV in LC
• If atherosclerosis + CRA hardens
and presses on CRV-lumen of CRV
further narrows-turbulence
increases
• Turbulence and pressure by CRA
causes endothelial damage of CRV
• Exposure of the collagen of vessel
wall-platelets aggregate and
thrombus formation takes place

16. PATHOLOGY
Ischaemic CRVO-haemorrhagic infarction of the retina-the inner retinal layers
Neovascularization of the iris and angle
Later changes include thickening of the retina and reactive gliosis
Note the intraretinal haemorrhages in various layers of the retina(arrows) and the eosinophilic
proteinaceous exudates in the outer plexiform layer (asterisk) and subretinal space (S)

17. CLINICAL FEATURES-PRESENTATION
Sudden UNILATERAL painless DECREASE of vision
Fairly sudden decrease but not as much as CRAO
Decrease of vision varies from just blurring of vision to severe loss of vision
No redness,pain or watering in fresh cases in most cases
Very few patients may have mild redness and photophobia on the initial few days or few weeks
If a patient presents with pain and severe redness it is due to NVG a complication of CRVO-LATE
Asymptomatic –routine examination may reveal old CRVO

18. SIGNS
Decreased V/A, RAPD,Fundus findings
Degree/severity of the clinical features depend upon the type of CRVO

19. Classification of CRVO
Ischaemic (non-perfused or haemorrhagic )-20%
Non-ischaemic (perfused)-80%
Indeterminate group where the definite classification
in to ischaemic or non-ischaemic is not possible

20. Why classification is important?
To predict the risk of neovascularization and NVG
To give visual prognosis
Decision as to appropriate follow-up intervals
Treatment to initiate in cases of CRVO with macular oedema

21. CLINICAL EXAMINATION
V/A-HM to 6/9 depending upon ischaemic or non-ischaemic
Extremely important to record the presenting BCVA
RAPD+,strongly positive in ischaemic cases
SLE Biomicroscopy-rarely circumciliary congestion,AC clear or few cells,iris-look for
NVI in undilated eye
Gonioscopy to rule out NVA
IOP-usually low in initial phase in non-glaucoma patients,important to rule out
glaucoma in both eyes

22. CRVO-FUNDUS
Findings vary according to ,whether it is ischaemic or non-ischaemic
Fundus findings like haemorrhages,cotton-wool spots are less marked in non-ischaemic
Media –usually clear – rarely there may be vitreous haemorrhage in fresh cases of CRVO
Disc – may be normal (NI) or hyperemic,swollen,covered and surrounded by haemorrhages
and cotton-wool spots(I)
Disc cup may or may not be obliterated
Venous pulsations are absent

23. Obliterated cup,borders
blurred,hyperemic,haemorrhages and cotton-
wool spots on the disc & surrounding

24. Retinal findings in CRVO
VEINS-markedly dilated,tortuous and dark colored-blood flow is slow
RETINAL HAEMORRHAGES- most important and obvious sign
All shapes of haemorrhages seen
Superficial haemorrhages +++,confluent,some large haemorrhages covering the underlying retina,dot and
blot haemorrhages
Haemorrhages more in the posterior pole covering macula
Sometimes haemorrhages break in to subhyaloid space and vitreous
BLOOD AND THUNDER APPEARANCE OR TOMATO KETCHUP APPEARANCE
COTTON-WOOL SPOTS are common and are scattered

25. Veins-dilated,tortuous,dark,cotton wool
spots

26. Confluent Haemorrhages

27. Retinal Oedema

28. Ischaemic CRVO

29. FUNDUS
Microaneuryms are not seen in acute stage
MACULA
May appear normal in non-ischaemic or few haemorrhages
Haemorrhages +++ in ischaemic
Edema –diffuse or cystoid
Subretinal fluid may be +
Visual loss occurs because of macular edema ,ischaemia,capillary non-perfusion,overlying
haemorrhages(either retinal or vitreal) or a combination of all these

30. LE macular edema

31. Course of CRVO
Haemorrhages ,cotton-wool spots,venous dilatation and tortuousity-
gradually disappear over many months
Few flame-shaped haemorrhages and dot haemorrhages ,cotton wool
spots- may remain for years

32. Opticociliary shunt vessels
• Optico ciliary shunt vessels may develop in
about 50% of patients on the disc surface- 3
to 14 months
• These are collateral vessels between the
obstructed disc capillaries and the
unobstructed choroidal or pial capillaries
• SIGNIFICANCE-These retinochoroidal
collateral veins,may protect against anterior
segment neovascularization but may not be
associated with a better visual prognosis

33. Opticociliary shunt vessels
These are differentiated from NVD by
Not discrete vessels,they are like bag of worms,larger
FFA-no leak

34. CRVO-late changes
Sheathing of veins around the disc
The disc-nearly normal/some blurring
of the margins/sometimes optic
atrophy is present
Rarely NVD

35. INVESTIGATIONS
Systemic –BP and systemic evaluation
Lab – CBC,ESR,peripheral smear,BS,lipid profile
OCT
FFA
ERG
Visual field – perimetry
In most patients who are older with known risk factors
OCT,FFA,BP,CBC,ESR,BS are enough

36. However in younger patients(<50 years) with no systemic known risk
factors more extensive investigations are needed to assess the possible
etiology
Rule out sarcoidosis,Behcet’s disease and other collagen vascular disorders (
x-ray chest,ACE,HLA typing,systemic work up)
Plasma homocystein levels
Anti phospholipid levels
Protein C, PROTEIN S levels,Factor V Leiden factor levels
Rule out hyperviscosity syndromes-leukemias,macroglobulinemia etc.
Rule out oral contraceptives in females

37. FFA in Ischaemic CRVO
Dye fills up delayed in venous tree and
capillary networks
Blockage of fluorescence due to retinal
haemorrhages
Extensive leaking of fluorescein into the
retina – in macular area
FAZ may be enlarged
Capillary non-perfusion in mid-periphery
>10 DD may be masked by haemorrhages
Late-phase photographs show patchy
extravascular areas of fluorescence and
staining of the retinal veins

38. FFA in Non-ischaemic CRVO
A prolonged venous transit time
Mild staining of the walls of veins,and
varying degrees macular leakage may be
present(including cystoid macular edema)
Capillary nonperfusionis not a prominent
feature
If present<10DD areas in mid-periphery
Also it is difficult to interpret FFA in fresh
cases because of blocking of fluroscein by
haemorrhages

39. FUNDUS AUTOFLUORESCENCE
Perivenular hypoautofluorescence with fern-like appearance in patients with recent-onset CRVO

40. OCT
Extremely useful non-invasive technique to
examine the macula
Useful in initial assessment and for follow-up
during treatment
May be normal in non-ischaemic
Macular edema – spongy,cystoid,SRF
Late cases may show atrophy of
retina,RPE,PTMH,FTMH OR ERM

41. Other investigations
• ERG-reduced b wave
amplitudes in ischaemic cases
• ERG- B/A ratio 60% of the
normal both scotopic and
photopic
• Perimetry-in ischaemic cases
contracted visual fields and
central field defects

42. Complications of CRVO
Neovascular glaucoma
Macular edema
Vitreous haemorrhage
Optic atrophy

43. Ischaemic VS Non-ischaemic CRVO
Factor Ischaemic CRVO Non-Ischaemic CRVO
Age Older age (68 yrs) Younger by 5 yrs (63 yrs)
V/A Poor initial vision
90% have VA<3/60
Better initial vision
>60% have VA>6/60
RAPD Strong RAPD Absent or mild
Disc Swollen Not swollen or mild
Retinal haemorrhages,CWS ++++ ++
Macula Haemorrhages,edema++ Less marked or normal

44. Factor Ischaemic CRVO Non-Ischaemic CRVO
Visual Field Reduced VF with central
scotoma
Normal or less reduced
ERG Reduced B wave Normal or borderline
FFA Drop out areas >10DD,leakage
in macular areas,staining of
veins
Less drop out areas
<10DD,less marked
leakage
NVI/NVA More common Less common
NVG Common upto 25% Less common <10%
Prognosis for VA Not good Good

45. TREATMENT OF CRVO
AIMS OF TREATMENT:
Reverse the obstruction in the
CRVO
Establish collaterals to by pass
the obstruction
Prevent the complications-
NVG
Treat the complications-
macular edema and NVG

46. 1.) SYSTEMIC THERAPY –
Systemic anticoagulation
Haemodilution
Systemic immunosuppression
2.) PHOTOCOAGULATION-
Panretinal photocoagulation(PRP)
Choriretinal venous anastomosis
3.) PHARMACOTHERAPY-
Intravitreal triamcinolone acetonide/other corticosteroids
Intravitreal anti-VEGF agents (e.g.-Bevacizumab)
Pharmacotherapies combined with PRP

47. 4.) SURGICAL THERAPY-
Pars plana vitrectomy (PPV) with R-TPA injection in to the vein
PPV with removal of posterior hyaloid and/or internal limiting membrane
PPV with radial optic neurotomy/laminar puncture
PPV with retinal endovascular surgery
PPV with chorioretinal venous anastomosis

48. Treatment of CRVO
None of the studies have been shown to be effective in
REVERSING THE OBSTRUCTION
IMPROVING VISION IN ISCHAEMIC CRVO

49. A. Reverse the CRVO
• Thrombolysis by recombinant tissue
plasminogen activator r-TPA given iv and
intavitreally
• r-TPA was also injected into the CRV itself
after PPV
• Haemodilution (heparin,erythrocytopherisis)
• PPV with optic radial neurotomy
• DON’T STOP ANTI-COAGULANTS IF THEY ARE
ALREADY ON IT
• ANTI-COAGULANTS CAN BE HARMFUL FOR
CRVO

50. B. Establish collaterals to relieve the obstruction
• Using Argon Laser-nasal to the
disc cause a break in the
Bruch’smembrane and then
cause a small hole in the vein
near the area of Bruch’s
membrane break. Chorioretinal
venous anastomoses develop-
thus retinal circulation bypasses
the CRV. However,it is
recommended for non-
ischaemic type only.

51. C. Prevent complications
The most important complication is NVG
CVOS study showed that to prevent NVG- apply PRPC only if any NVA or two
clock hours of NVI develop and not before that

52. D. Treat Complications
1. Macular oedema-
It is an important cause of reduction in VA in CRVO and BRVO
Macular oedema in ischaemic cases is not amenable to treatment
But there are many options to treat in non-ischaemic cases
Role of macular grid photocoagulation in CVO related macuar oedema
Not effective- proved by randomized study of 155 cases of CVO
CVOS STUDY

53. Treatment
modalities
for macular
edema
1.) INTRAVITREAL STERIOD INJECTION AND IMPLANTS
Triamcinolone -SCORE STUDY
Dexamethasone depot-Ozurdex implant -GENEVA
TRIAL
Fluocinolone implant-ILUVIEN implant
2.) INTRAVITREAL ANTI-VEGF INJECTION
Bevacizumab(Avastin)
Ranimizumab(Lucentis) -CRUISE STUDY
Afibercept (Eyelea)-COPERNICUS STUDY
3.)PPV with ILM PEELING FOR RESISTANT EDEMA

54. Intravitreal TA steroid injection
Cheap,lasts for 3 months
The SCORE (Standard care vs Corticosteroid for Retinal vein occlusion)study
showed that
Intravitreal injection of 1 mg or 4 mg
Gain of 15 letters or more of vision occurred in 27% in injection group
against 7% only in observation
It is better to use 1 mg dose than 4 mg for its safety profile

55. ADVANTAGES –
Cheap
Easy treatment
DISADVANTAGES are side effects-
Effect lasts for 3 months so repeat injections are needed
Raised IOP in 35% needing medications and surgery
Cataract (90%)
Endophthalmitis
Are sparingly used now after the availability of anti-VEGF drugs

56. Intravitreal steroids-depot injections
New intravitreal slow release
biodegradable device with
dexamethasone-ozurdex-0.7mg
Advantage-effect lasts for 3-6
months
IOP,cataract concerns remain
however but are less marked
than triamcinolone injection

57. GENEVA TRIAL FOR OZURDEX IMPLANT

58. ANTI-VEGF INJECTIONS
1.25 mg
0.5mg 2mg

59. BEVACIZUMAB (Epstein et al)
Monthly injections for
6 months ,increased
VA by 16 letters-3
lines
Delayed treatment
especially in older
individuals yielded
poorer results

60. RANIBIZUMAB (CRUISE TRIAL)
Ranibizumab 0.3mg and 0.6mg or sham injections were used in 3 groups of
patients (130 patients in each group)
All CRVO were perfused
Gain of>15 letters 47-50% in ranibizumab vs 33% in sham group at the end
of 12 months
Mean change in VA was 13-14 letters in lucentis group vs 7 letters in sham
group

62. AFLIBERCEPT OR EYELEA
A new drug that traps VEGF
VEGF receptor fusion protein-DECOY-that binds all forms of VEGF-A,along
with placental growth factor(PIGF),another member of the VEGF family was
also believed to be implicated in the development of wet age related macular
degeneration(AMD)
It is supposed to have more affinity for VEGF than the natural receptors of
VEGF

65. Which anti-VEGF is better?
Avastin,ranibizumab and aflibercept were shown to be equally effective in ME associated with
non-ischaemic CRVO

66. Anti-VEGF
DISADVANTAGES-
Need to be given every month for 3 months—then sos
First year as many as 10 injections
Recurrence of edema is common
Regular follow-ups are needed
Systemic side-effects are a concern
Cost of ranibizumab and eyelea/aflibercept are
prohibitive
Endophthalmitis and RD are rare but do occur
ADVANTAGES-
Improves VA
Decreases ME
Reduce chances of NVA and NVI
Easy treatment
Whether is prevents conversion to ischaemic
type is not known

67. Anti-VEGF
V/S
Intravitreal
steroid
implant
Both are effective for macular edema associated
with CRVO
Steroid implant-effect lasts for 3 months so cost
effective and systemic side effects are not known
but IOP and cataract are concern
Anti-VEGF- no cataract or IOP spikes and very
effective in improvement of VA but more repeated
injections and cost are concern
A meta analysis favored –anti-VEGF’s over steroid
implants

68. D. Treat
Complications
2.Neovascular Glaucoma
PRPC
Anti-glaucoma medications
Atropine, steroid drops
Anti-VEGF injection
Shunt surgery
Cyclo-destructive procedures

69. D/D CRVO
Ocular ischaemic syndrome
Hyperviscosity retinopathy
Diabetic retinopathy
Papilledema

70. THANK YOU !