This document provides information on central retinal vein occlusion (CRVO), including its prevalence, risk factors, pathogenesis, clinical presentation, investigations, complications, and differences between ischemic and non-ischemic CRVO. Some key points are: CRVO affects around 0.8 in 1000 people over 30 years old and is more common in older patients and those with hypertension, diabetes, or cardiovascular disease. It occurs when a thrombus forms in the central retinal vein, often at the level of the lamina cribrosa. Presentation includes sudden unilateral vision loss. Fundus findings include dilated, tortuous veins and retinal hemorrhages. Classification as ischemic or non-ischemic determines risk of neovascularization and visual prognosis.

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 PREVALENCE & INCIDENCE
 Prevalence- CRVO was 0.8/1000 and BRVO was 4.4/1000 population aged 30 years and above
(5.2/1000)
 Incidence- RVO 16 per 10,000/year in persons aged 50 years and above – CRVO is
3/10000,BRVO is 13/10000 per year

4. 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

5. 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

6. 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

7. H) Myeloproliferative disorders ( to be considered in pts < 45 yrs )-
STASIS OF BLOOD FLOW
Polycythemia
Abnormal plasma proteins ( myeloma,waldenstrom macroglobuinaemia )
Leukiamias
i) Thrombophilic disorders ( to be considered in pts < 45 yrs)-
HYPERCOAGULABILITY
 Hyperhomocysteinaemia
Anti-phospholipid antibodies ( lupus anticoagulant & anti-cardiolipin )

8. 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)

9. 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

10. Ocular risk factors Eale’s disease

11. Carotid cavernous fistula

12. RISK FACTORS FOR RVO

13. PATHOGENESIS
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

14. 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

15. 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

18. Damage to retina and vision depend upon
1. Rapidity of development of CRVO
2. Degree of occlusion-mild,moderate or severe
3. Availability of collateral pathways

19. PATHOLOGY
Ischaemic CRVO-haemorrhagic infarction of the retina-the inner retinal layers
Neovascularization of the iris and angle
Less frequently – NVD NVE rare
Later changes include thickening of the retina and reactive gliosis

20. HISTOPATHOLOGY
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)

21. 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

22. SIGNS
Decreased V/A, RAPD,Fundus findings
Degree/severity of the clinical features depend upon the type of CRVO
Two types are recognized-ischaemic and non-ischaemic

23. 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

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

25. CLINICAL EXAMINATION
V/A-HM to 20/30 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

26. 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 or hyperemic,swollen,covered and surrounded by haemorrhages and
cotton-wool spots
Disc cup may or may not be obliterated
Venous pulsations are absent

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

28. 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

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

30. Confluent Haemorrhages

31. Retinal Oedema

32. Ischaemic CRVO

33. All shapes of haemorrhages seen

34. 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

35. RE CRVO macular edema with
haemorrhages

36. LE macular edema

37. 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
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
Blood flows from high pressure retinal circulation to low pressure choroidal circulation

38. Opticociliary shunt vessels
They are differentiated from NVD by
Not discrete vessels,they are like bag of worms,larger
FFA-no leak
These retinochoroidal collateral veins,may protect against anterior segment neovascularization
but may not be associated with a better visual prognosis

39. 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

40. Chronic changes-MACULA
Macular cysts and macular edema
Macular hole- PTMH or full thickness
Pigment clumping or stippling or atrophy in macula
Persistent macular haemorrhages,even years after the occlusion may +
Hard exudates with irregular circinate configuration around the macula and become more
prominent months later
Occasionally an epiretinal membrane

41. 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

42. 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

43. 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

44. FFA in Non-ischaemic CRVO
A prolonged venous transit time
Mild staining og 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

45. FFA in ischaemic VS non-ischaemic CRVO
The amount of non-perfusion or ischaemia is determined by inspecting the fluorescein
angiogram-MIDPERIPHERY
In ischaemic cases drop out areas measure >10 DD or more and in non-ischaemic they measure
<10 DD.
Also it is difficult to interpret FFA in fresh cases because of blocking of fluroscein by
haemorrhages

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

47. Further course
Some eyes with non-ischamic CRVO convert to ischaemic type upto 34%-----half of them within
4 months rest upto 3 years
?progression of the vein occlusion or ? Progressive retinal capillary nonperfusion is unknown
Conversion is higher for older patients
Macular edema is most important cause of DOV in those who are not converting into ischaemic
type
Pigmentary changes in macula can be late changes

48. 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

49. 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

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

51. OCULAR RISK FACTORS FOR NVI/NVA
Poor initial visual acuity(P<0.001)
Amount of non-perfusion seen by fluorescein angiogram(P<0.001)
VENOUS TORTUOSITY(P=0.02)
Extensive retinal haemorrhages(P=0.07)
Duration less than 1 month(P=0.08)
CVOS STUDY 726 EYES

52. Neovascularization in CRVO
Iris (NVI) and angle- NVA
NVD rare,NVE is extremely uncommon
NVA can develop from 2 weeks to years after
CRVO-so follow up every 2 weeks initially
Most occur within 3-6 months
NVI/NVA seen in 35% (61/176) of
ischaemic/indeterminate CRVO and
10%(56/538) in non-ischaemic CRVO
Not all cases of NVI/NVA are NVG
CVOS STUDY-726 EYES

53. Incidence of NVG
Incidence varies
2% in CRVO study and 23% in some other studies
Do gonioscopy every 2 weeks in ischaemic cases
CVOS STUDY-726 EYES

54. 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

55. Factor Ischaemic CRVO Non-Ischaemic CRVO
Visual Field Reduced VF with central scotoma Normal or less reduced
ERG Reduced B wave Noraml 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

56. Which signs and tests best detect/predict
ischaemic CRVO ?
RAPD
ERG
RAPD+ERG-predicted ischemic in 97% of cases
Perimetry – next most reliable
Visual acuity
FFA
Fundus appearance –least reliable

57. Few odd facts
Fellow eye in a patient with CRVO has 5% risk of developing CRVO in 3 years
Bilateral simultaneous CRVO is known to occur mainly in patients with systemic illnesses with
predisposition to CRVO
CRVO can occur with cilioretinal artery occlusion or with CRAO

58. 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

59. 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)
Pharmacitherapies combined with PRP

60. 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

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

62. 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)
Anticoagulants-aspirin and antiplatelet drugs
PPV with optic radial neurotomy
DON’T STOP ANTI-COAGULANTS IF THEY ARE
ALREADY ON IT
ANTI-COAGULANTS CAN BE HARMFUL FOR
CRVO

63. B. Establish collaterals to relieve the
obstruction
By LASER- use argon laser to cause a break in the Bruch’smembrane and then cause a small
hole in the vein near the area of Bruch’s membrane break. Anastomoses develop-thus retinal
circulation by passes the CRV. However,it is recommended for non-ischaemic type only.

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

65. D. Treat Complications
1.Treatment of NVG-
PRPC
Anti-glaucoma medications
Atropine, steroid drops
Anti-VEGF injection
Shunt surgery
Cyclo-destructive procedures

66. 2. 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
CVO STUDY

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

68. 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

69. 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

70. 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

71. GENEVA TRIAL

72. ANTI-VEGF INJECTIONS

73. 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

74. 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

77. 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

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

81. 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 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

82. 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

83. THANK YOU !