This document discusses retinal vein occlusion, specifically branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). It covers the epidemiology, risk factors, pathogenesis, clinical presentation, treatment options including laser photocoagulation, corticosteroids and anti-VEGF drugs, and complications such as macular edema and neovascularization. Key points include that BRVO most commonly affects the superotemporal quadrant and that perfusion status on fluorescein angiography helps determine prognosis for CRVO.

1. Retinal vein occlusion
Sumit Singh Maharjan

2. Classification
Branch retinal vein occlusion
Central retinal vein occlusion

3. Branch Retinal vein occlusion (BRVO)
Epidemiology:
• Beaver Dam study- 15 years cumulative incidence 2-3% with 78%
being BRVO.
• M:F – equal
• 60-70 years

4. Risk factors and Associations:
• HTN
• Arteriosclerosis
• DM
• Smoking
• Hyperlipidemia
• Glaucoma
• Ocular inflammatory disease
• Antiphospholipid antibodies
• Elevated homocysteine levels
• Low serum folate levels
• Shorter axial length
• High HDL
• Light to moderate alcohol
consumption

5. Pathogenesis:
• Lumen of the vein may be compressed up to 33% at the crossing site
• Vitreous may also play a role in compression of susceptible AV
crossing sites

6. Some have postulated:
Turbulent blood flow at crossing site
Focal swelling of endothelium and deeper vein wall tissue
Venous obstruction
Other reports:
Actual venous thrombus formation at the point of occlusion

7. Venous obstruction
Elevation of venous pressure
Overload the collateral draining capacity
Macular edema and ischemia
Unrelieved venous pressure can result in rupture of vein wall with
intraretinal hemorrhage

8. Vision loss from RVO is due to:
• Macular ischemia
• Macular edema
• Complications from neovascular disease

9. Clinical features
Symptoms:
• Sudden painless loss of vision
• Visual field defect
• Subclinical presentation may occur if tributaries distal to macula or
nasal vein involved
• Sometimes floaters- from a vitreous hemorrhage

10. Signs:
BRVOS defined ischemic BRVO as those with greater than a total of 5
disc diameters of non perfused on FA.

11. Location of venous blockage determines the distribution of the
intraretinal hemorrhage
• If the venous obstruction at optic disc – 2 quadrants of fundus
involved
• If the obstruction is peripheral to disc – 1 quadrant or less may be
involved
• If the venous blockage is peripheral to tributary veins draining macula
– there may be no macular involvement and no decrease in vision

12. • The most common location for BRVO is in the superotemporal
quadrant (63%)
• Over time the intraretinal hemorrhage may completely resolve.
• Without characteristic segmental distribution of intraretinal
hemorrhage, it will be difficult to diagnose, but segmental
distribution of retinal vascular abnormalities that occurred during the
acute phase persists and be apparent on FA.

13. • In chronic phase of the disease, after intra retinal hemorrhage
absorption the diagnosis may depend on detecting segmental
distribution of retinal vascular abnormalities that include capillary
non perfusion, dilatation of capillaries, micro-aneurysms,
telangiectatic vessels and collateral vessel formation.

14. Complications:
1. Macular edema
2. Macular ischemia
3. Sequelae of neovascularization
• BRVOS – 31-41% pt with ischemic BRVO developed neovascularization
compared to 11% of pt with non ischemic.
• Among those 31-41%, 60% developed periodic vitreous hemorrhage
• Retinal neovascularization typically develops at 6-12 months but may
occur later
• NVI/ NVA develops in 1% eyes in BRVO.

15. D/D:
• Hypertensive retinopathy
• Diabetes retinopathy
• Radiation retinopathy
• Macular telangiectasia
• Retinal angiomatous proliferation

16. Clinical evaluation
1. Clinical examination
2. FA:
• To help verify the diagnosis and evaluate for complications
• Only technique that will accurately define the capillary abnormalities
in BRVO
3. wide field angiography
4. OCT: most important imaging modality in the treatment of patient
with BRVO and macular edema
• Non invasive and rapid method of quantitatively measuring macular
edema

17. Characteristic findings in FA:
• Varying amount of capillary nonperfusion, blockage from intraretinal
hemorrhage, microaneurysms, dilatation of capillaries, telangiectatic
vessels and collateral vessel formation are encountered.
• In chronic cases, only FA can determine old BRVO

18. Prognosis
• IF FA demonstrates – macular leakage and edema with cystoid
involvement of fovea but no capillary nonperfusion – then 1/3rd
resolve vision and if duration > 1 year then decrease chance of regain
of vision.
• When macular edema is present within 6 months of BRVO no or little
leakage in FA – vision regains normally

19. Work up
Diagnostic workup should be done in young patient for:
• HTN
• DM
• H/O contraception use
• H/O drug use that promote hypercoaguloble state
• Infectious disease: lyme, HIV, syphilis
• Inflammatory disease

20. In suspected inflammatory or coagulopathy
• CBC
• PT/INR
• Lipid profile
• S. homocysteine
• Anticardiolipin
• Antinuclear antibodies
• In B/L or numerous BRVO – look for infections or inflammations or
hypercoagulopathy

21. Treatment
Medical treatment:
• In hypercoagulopathy – anticoagulant may be given, (no role in
prevention and management in most cases). So generally not
indicated

22. Laser treatment:
BRVO study for macular edema:
• Argon laser photocoagulation (grid pattern) may reduce visual loss
from macular edema
Results in thinning of retina (outer retina)
Reducing oxygen consumption and increasing choroidal delivery of
oxygen to the inner retina
Produces auto regulatory constriction of the retinal vasculature in the
leaking area
decreases the edema

23. • For grid treatment – argon blue green wavelength is used
• Krypton red and argon green are absorbed less than blue green by the
xanthophyll pigment of the inner retina that is present in increased
concentration close to the foveal center.

24. General guidelines from BRVOS for macular
edema
• Wait 3 – 6 months before considering laser therapy
• If the vision is reduced to 20/40 or worse, wait 3 – 6 months for
sufficient clearing if retinal hemorrhage to permit high quality FA and
then evaluate for macular edema and macular ischemia
• If perfused macular edema accounts for the vision loss and vision
continues to be 20/40 or worse without spontaneous improvement
consider grid macular photocoagulation
• If macular ischemia accounts for the visual loss no laser treatment is
recommended.

25. BRVOS for neovascularization
• Prophylactically scatter laser photocoagulation can lessen subsequent
neovascularization complications
• If neovascularization already exists that laser can lessen subsequent
vitreous hemorrhage
• But it is recommended that laser be applied only after
neovascularization is observed
• BRVOS – strongly suggests that laser after development of
neovascularization is as effective in preventing vitreous hemorrhage
as is laser before the development of neovascularization
• After laser vitreous hemorrhage incidence reduced from 60 % to 30%

26. Steroid treatment
SCORE study (standard care vs corticosteroid for retinal vein occlusion
study)
• Effective and safety of intravitreal triamcinolone acetate for the
treatment of macular edema
• IVTA not recommended as 1st line therapy for macular edema in
BRVO. However can be considered if laser or anti VEGF are ineffective

27. GENEVA study (Global evaluation of implantable dexamethasone in
retinal vein occlusion with macular edema in BRVO and CRVO.
• Dexa implant is an alternative treatment to macular grid laser in the
appropriate patient (i.e. no glaucoma and pseudophakic)

28. Anti VEGF
• In patient of BRVO, retinal ischemia leads to secretion of VEGF which
leads to increased vascular permeability, vasodilatation, migration of
endothelial cells and neovascularization
• Increased vascular permeability and vasodilatation leads to retinal
edema
BRAVO (Branch retinal vein occlusion study)
• Efficacy and safety of ranibizumab in the treatment of macular edema
from BRVO
• Study shows ranibizumab is superior to traditional laser for the
treatment of macular edema

29. Current recommendation
Macular edema from BRVO
Monthly injection of 0.5mg ranibizumab
If treatment fails after 3 months
Traditional grid macular laser
(If capillary non perfusion explains vision loss then laser is not
indicated)

30. Experimental treatment
FAVOR study
• Intravitreal implant of fluocinolone acetonide

31. Surgical management
Vitrectomy with or without sheathotomy
• Removal of the compressive factor by sectioning the adventitial
sheath may be effective
• Due to risk of intraoperative complications and availability of less
invasive alternatives this is not indicated as 1st line treatment
• Vitreous surgery: in non clearing vitreous hemorrhage, epiretinal
membranes or TRD with macular involvement

32. Central retinal vein occlusion (CRVO)

33. Epidemiology
• M:F – equal
• More above 65 years old
• Prevalence in population based study: 0.1 – 0.4%
• Usually U/L disease but may develop RVO in fellow eye in 1 % patient
within 1 year and estimated 7 % of patient within 5 years

34. Associations and risk factors with CRVO:
• Systemic vascular disease: DM, HTN, carotid insufficiency
• Ocular disease: POAG, ischemic optic neuropathy, pseudotumor
cerebri, tilted optic disc, optic nerve head drusens
• Hematological alterations: hyperviscocity syndromes (polycythemia
vera, lymphoma, leukemia, sickle cell disease), anemia, elevated
plasma homocysteine, factor XII def, antiphosphilipid antibody
syndrome, protein c and s deficiency.
• Inflammatory/autoimmune vasculitis: SLE
• Medications: oral contraceptions, diuretics, Hep B vaccine
• Infectious vasculitis: HIV, syphilis, herpes zoster, sarcoidosis
• Others: after retrobulbar block, dehydration, pregnancy

35. Clinical features
• Sudden painless loss of vision
• Hemorrhage radiate from the
optic nerve head are variable in
quantity and may result in the
classic “blood and thunder”
appearance

36. • Cilioretinal artery occlusion can occur in association with CRVO
Together these occlusion have been hypothesized to constitute a
distinct clinical entity arising from a sudden increase in the intraluminal
capillary pressure due to CRVO
Inducing relative occlusion of the cilioretinal artery whose perfusion
pressure is lower than the central retinal artery

38. CVOS
• VA at the time of presentation was variable but an important
prognostic indicator of final visual outcome
• Of those initial VA 20/40 or better – majority maintain VA
• Intermediate VA (20/50 to 20/200) – variable outcome
• Poor VA at onset (20/200 or less) – 20% chance of improvement
• In CVOS – worse VA correlated with development of NVI/NVA
• NVA may be present without NVI in 12%.

39. Perfusion status
• CVOS classified perfusion status of CRVO – perfused, non perfused or
indeterminate based on FA characters
Perfused CRVO (non ischemic/incomplete/partial)
• Demonstrates less than 10 disc areas of retinal capillary nonperfusion
on FA
• These eyes typically have less intraretinal hemorrhage and better
initial VA

40. Non perfused CRVO (ischemic/hemorrhagic/complete)
• Demonstrates 10 or more disc areas of retinal capillary nonperfusion
on FA
• Greater degree of intraretinal hemorrhage, macular and disc edema
and worse VA at onset
Indeterminate:
• When there is sufficient intraretinal hemorrhage to prevent
angiographic determination of perfusion status.

41. Other examination features that may help in determining the perfusion
status in the acute phase of CRVO include:
• Baseline VA
• RAPD
• Electro-retinography (negative wave form is seen)
• Goldmann perimetry

42. CVOS classification of initial perfusion status of the CRVO was
important for determining the natural history of the disease
• Poor VA and larger areas of non perfusion – Increased risk of NVI/NVA
• Perfused – 10% chance of NVI/NVA
• Non perfused or indeterminate: 35% chance of NVI/NVA
• At 3 years – 45% chance of developing neovascular glaucoma after
onset of ischemic CRVO
• Overall – 34% of initially perfused eyes converted to non perfused
after 3 years.

43. Pathogenesis
• Pathophysiology not clearly understood

44. Within the retrolaminar portion of optic nerve
Central retinal artery and vein are aligned parallel to each other in
common tissue sheath
CRA and vein are naturally compressed as they cross the rigid shieve
like openings in the lamina cribrosa but typically gives off branching
collaterals vessels just piercing the lamina
These vessels may compress from mechanical stretching of lamina as
with increase in IOP which may cause a post bowing of the lamina and
subsequent impingement on the vein

45. • Furthermore, local factors may predispose to occlusion of veins,
including compression by an atherosclerotic central retinal artery or
primary occlusion of the central retinal vein from inflammation
• Hemodynamic alterations: produce stagnant flow and subsequent
thrombus formation in the CRV including diminished blood flow,
increased blood viscocity and an altered lumen wall (Virchow’s triad)

46. • In experimental trial – occlusion of both retrolaminar CRA and vein
posterior to lamina and prior to the branching of collateral channels
from the main trunk was required to produce ischemic CRVO
• It is hypothesized that a non ischemic CRVO may be due to occlusion
of the CRV at a site further posterior, allowing normal collateral
channels to provide alternatives routes of venous drainage
• Neovascularization of the anterior and posterior segment and severity
of macular edema are modulated by growth factors released from
ischemic retina.

47. Treatment
• Treatment of CRVO is directed at treating the sequelae of CRVO
particularly macular edema and neovascularization
Treatment of systemic medical conditions if any:

48. Treatment of macular edema
• CVOS – grid laser photocoagulation not recommended
Corticosteroid therapy
• Maintain anti-inflammatory effects with modulation of production of
cytokines and growth factors including VEGF
• Also thought to stabilize BRB with reduction of vascular permeability

49. Score
• Showed significant improvement in VA with intravitreal triamcinolone
compared to observation
• The limited duration of the response to IVTA therapy has prompted
the development of sustained release steroids (intravitreal
fluocinolone acetonide)
• But with sustained release all phakic pt developed visually significant
cataracts and 92% developed increase IOP

50. Intra vitreal Anti VEGF therapy
VEGF
cause capillary endothelium cell proliferation
Progressive vascular closure and non perfusion in CRVO
• Anti VEGF – enhance blood flow, lower intravenous pressure and
normalize venous diameter and tortuosity.

51. Treatment of ocular neovascularization
Laser photocoagulation:
• CVOS recommends PRP be delivered promptly after the development
of NVI/NVA but not prophylactically in eyes with nonperfused CRVO
• In 90% cases, NVI/NVA resolve in 1 to 2 months after PRP
Persistent neovascularization after PRP
Close observation
Additional PRP may be applied to halt its progression.

52. • Patient with NVD/NVE without NVI/NVA should be treated with PRP
to prevent anterior segment neovascularization
Medical therapy
• Topical/systemic anti glaucoma agents to reduce IOP
• Topical steroids to reduce inflammation
• Cycloplegics to prevent from posterior synechiae

53. Alternative treatment
Chorioretinal venous anastomosis:
• In eyes with perfused CRVO – investigators have bypassed the
occluded central retinal vein by creating a chorioretinal anastomosis
between nasal branch retinal vein and choroidal circulation.
Tissue plasminogen activator:
• Thrombolytic agents in suspected thrombus in the central retinal vein
• TPA converts plasminogen to plasmin which destabilize intravascular
thrombi
• Can be administered systemic, intravitreal and by endovascular
cannulation of retinal vessels

54. Surgical treatment
Vitrectomy
• PPV may be useful to address complication of CRVO and even to
attempt to alter the natural course of the disease
Indicated:
• Non clearing vitreous hemorrhage
• Removal of epiretinal membranes and fibrovascular proliferation if
present and placement of complete endolaser PRP at the time of PRP
• In eyes with extensive anterior segment neovascularization and
neovascular glaucoma, PPV and endolaser may be combined with
pars plana placement of a glaucoma drainage device to avoid anterior
chamber hemorrhage at the time of tube placement

55. • Potential role for PPV with peeling of ILM has also been investigated
for treatment of CME secondary to CRVO
Radial optic neurotomy:
• Combined with PPV with radial optic neurotomy (RON) involving
transvitreal incision of the nasal scleral ring to release pressure on the
central retinal vein at the level of scleral outlet

56. General guideline for CRVO
• Treat any associated intraocular neovascularization with PRP
• Treat associated macular edema, if visually significant, with an intra
vitreal Anti VEGF or steroids
• VA loss from macular edema does not improve with grid laser
• Lower IOP if elevated
• Treat underlying medical conditions

57. References
• Ryan’s 5th edition
• Myron yanoff 4th edition
• American academy of Ophthalmology-sec 12, 2013,2014
• Kanski’s clinical ophthalmology 8th edition