ANGGUN RAMA YUDANTHA

Vitreoretinal Division
Ophthalmology Department - Universitas Indonesia
Cipto Mangunkusumo Hospital - Jakarta
The Occlusion

Artery or Vein
Branch or Central
 Central Retinal Artery Occlusion

• First described by Von


Graefe 1859  patient
with endocarditis
• Incidence 1,9/100.000 in
USA
• 80% has bad visual
outcome
• Cilioretina artery
preserves visual acuity
20/50 or better
 Central Retinal Artery Occlusion
• Sign and Symptoms :
• Painless
• Sudden decreased

visual acuity
• Quite eye
• RAPD is present
• Whitening of retina *
AND red spot on the
macula (cherry red
spot) *
• Boxcarring
phenomena or
cattle-trucking).
 Central Retinal Artery Occlusion


LATER...
• several weeks the obstructed vessel may be
recanalized allowing reperfusion of retinal vessels.
• The retinal edema resolves  The optic disk
eventually becomes atrophic.
• Neovascularization of the iris occurs in 16–18% of
eyes with CRAO  IOP examination
 CRAO MANAGEMENT


The management of CRAO divided into:
 Acute
 Attempt to restore ocular perfusion to the CRA.
 Subacute
 Preventing secondary neovascular complications to
the eye.
 Long term
 Preventing other vascular ischaemic events to the eye
or other end organ.
 Acute Management of CRAO


• The aim of the treatment :
▫ to restore the retinal blood supply
as soon as possible
▫ Increase oxygen delivery to the
retina
▫ limit the damage from hypoxia
 Acute Management of CRAO


Dislodge Emboli & increase retinal
perfusion:
 Ocular massage (three mirror lens)
 Reducing IOP: Intravenous acetazolamide and
mannitol, AC paracentesis
 Increase Blood O2 content & dilate retinal arteries
 Use of sublingual ISDN or pentoxifylline
 inhalation of carbogen (mixture of 95 % oxygen and 5 %
carbon dioxide), Hyperbaric oxygen.
 To lysis thrombus: thrombolytic therapy
 Ocular Massage

 Ocular massage includes the compression of the globe
with a three-mirror contact lens for 10 s, to obtain retinal
artery pulsation
 Alternatively, digital massage can be applied over the
globe over the closed eyelids for 15–20 min.
 Ocular massage causes retinal arterial dilatation and
large fluctuations in IOP.
 Ocular massage may mechanically facilitate the
disintegration of a thrombus, or dislodge an impacted
embolus into a more peripheral part of the retinal
circulation
Ocular massage

WARNING:

OCULOCARDIAC REFLEX
 AC Paracentesis

• To decrease IOP suddenly
• Some people perform in clinic (in front of
the slit lamp)  not recommended
(based on true story)
• Done in the clean room or OT with
microscope
• Can decrease IOP to 5 mmHg
 Anterior Chamber Paracentesis

• Patient lay flat


• Topical anesthesia
• Use tuberculin syringe and
27 to 30 G needle
• Aspirate 0.1 – 0.3 mm
• Through limbus with the tip
overlying the iris
Anterior Chamber Paracentesis

WARNING !!!

INFECTION
LENS TOUCHED
 Subacute Management of CRAO


 The reported prevalence on neovascularization after
CRAO varies from 2.5% to 31.6%
 Neovascularization after CRAO tend to occur around 8
weeks (range 2–16 weeks)
 Therefore, review all patients with acute CRAO at
regular intervals as early as 2 weeks, and then monthly
up to 4 months after CRAO.
 If at any stage, a patient develops neovascularisation,
panretinal photocoagulation should be performed
promptly.
 
PRP aims :
• to decrease demand
for oxygen in the
peripheral retina
• to reduce the vascular
endothelial vascular
growth factors that
cause abnormal blood
vessel.
 LONG TERM MANAGEMENT

The optimal management of CRAO needs to address

systemic atherosclerotic risk factors to reduce
secondary ischaemic events.
 Outcome

 Duration of visual impairment
 Presenting visual acuity
 Presentation of cilioretina artery (15% -
30% of population)
 Introduction

 Pathophysiology
 Mechanical (compression)
 Risk Factors
 Similar in BRVO and CRVO
 Site of occlusion : BRVO, Hemispheric RVO, CRVO
 Lamina cribrosa, arteriovenous crossing
 Extention of retinal vessel occlusion
 Ischemia , Non Ischemia
 Management
 Laser , Intravitreal Injection, Surgery
 PATHOPHYSIOLOGY

 Venous occlusion (thrombosis, Virchow’s rule)
 Blood flow stagnation
 Increased capillary & venous pressure
 Retinal hypoxia
 Endothelial cells damage  decreased function of
BRB
 Blood dan angiogenic mediators (VEGF)
extravasation & release

 RISK FACTORS

The Eye Disease Case-Control Study

 Age
 Hypertension
 Hyperlipidaemia (CRVO)
 Diabetes mellitus (CRVO)
 Glaucoma
 Oral contraceptive pill in younger females
 Smoking (BRVO)
 

SITE OF OCCLUSION
 Extention of vessel occlusion

 Presenting Visual Acuity
 The better VA  better outcome
 Relative Afferent Pupillary Defect (RAPD)
 Worse if marked
 Non perfusion area  FA examination
 Large area of non perfusion  ischemia type
 ERG
 b/a wave ratio
 B wave a sensitive index for retina ischemia

PROGNOSTIC FACTORS
 RVO: Milestones in Treatment
Laser
Photocoagulation
Steroids

Anti-VEGF

1977 1995 2004 2007 2009 2010 2011 2012 2013

CVOS1 SCORE2 GENEVA3 HORIZON5

COPERNICUS6
BRAVO
Treatment first used

Trial data first published GALILEO7

CRUISE4

Dashed lines = trials with CRVO and BRVO data (reported separately). RETAIN

SHORE

COMRADE-B
1. The Central Vein Occlusion Study Group. Arch Ophthalmol. 1995;102(10):1425-1433. COMRADE-C
2. Ip MS et al. Arch Ophthalmol. 2009;127(9):1101-1114.
3. Haller JA et al. Ophthalmology. 2010;117(6):1134-1146.
4. Brown DM et al. Ophthalmology. 2010;117(6):1124-1133. BRIGHTER
40
5.
6.
Heier JS et al. Ophthalmology. 2012;119(4):802-809.
Boyer D et al. Ophthalmology. 2012;119(5):1024-1032.
CRYSTAL
7. Holz FG et al. Br J Ophthalmol. 2013;97(3):278-284.
 Branch Vein Occlusion
Study (BVOS)

 a large, multicenter, prospective, randomized, controlled trial
 65% eyes gained > 2 lines of vision when treated with grid
photocoagulation. This was significantly different than the non-
treatment group, in which only 37% eyes experienced the same
gain in visual acuity.

 Conclusion :
 Grid laser should be performed in BRVO of 3 – 18
months duration if VA < 20/40 or FFA reveals ME
 Sector scatter laser in the treatment of
neovascularization if > 5DD of nonperfusion
Branch vein occlusion study group. Am J Ophthalmol 1984; 98:271-82
 Central Vein Occlusion
Study (CVOS)

 a large (n=725), multicenter, prospective, randomized,
controlled trial
 VA < 20/200 : 80% remains unchanged or deteriorated
 VA 20/50 – 20/200 : improved in 19%, remains stable in 44%,
and worse in 33%
 VA 20/40 : retained good acuity
 No benefit to early PRP in nonperfused CRVO
and that PRP should be reserved until
development of iris/angle neovascularization
 No difference in VA between treated and
untreated with grid laser for macular edema
Central vein occlusion study group. Online J Curr Clin Trials 1993 Oct 14; doc no95
 Intravitreal Steroids (SCORE)


Standard care versus COrticosteroid for REtinal
vein occlusion Study
A large, multicenter, prospective, randomized, controlled
trial in 630 cases CRVO/BRVO

Objective :
 To compare standard care with IVTA injection for the treatment of
macular edema secondary to retinal vein occlusion (CRVO and
BRVO)

 SCORE – Design

 Study enrollment :

 Group I : standard care
 Group II : IVTA 4 mg
 Group III : IVTA 1 mg
 Primary outcome :
 improvement by 15 or more letters at 1 year visit
 Secondary outcome :
 changes from baseline in best corrected VA score
 changes in retinal thickness (stereoscopic color
fundus photography and OCT)
 adverse ocular outcomes
 SCORE - Result

 The SCORE-BRVO results (12 months follow-up) : no
statistical difference laser-treated and IVT groups in
regards to VA.

 The SCORE-CRVO trial shows significant improvement in VA

compared to control. At 12 months, 27% of patients treated
with 1 mg IVT and 26% of 4 mg-treated patients gained 15 or
more letters. This were significantly different from the 7% of
control group.

 Due to a higher incidence of elevated IOP and cataract in the 4 mg injection

group, it was recommended that 1 mg IVT was superior to control group.
 Anti VEGF

• The anti-VEGF agents block the VEGF molecules
• Decreasing the abnormal and harmful new blood vessels
formation
• Decreasing the leakage and swelling of the retina.
• Leads to stabilization of vision and even improvement in vision

(Lucentis/Patizra)
PEGABTANI BEVACIZUMA RANIBIZUM AFLIBERC
B B AB EPT
Bervolt Study


Bervolt study

Ranibizumab Studies - BRVO

BRAVO1 RETAIN3 BRIGHTER5
N=397 N=34/66 N=455
Extension of BRAVO and 0.5 mg ranibizumab
0.3 mg and 0.5 mg HORIZON
ranibizumab versus 0.5 mg ranibizumab PRN ± laser versus
sham PRN extension trial laser

2010 2011 2012 2013 2014 2016

HORIZON2 SHORE4 COMRADE-B6

N=304/608 N=115/202 N=244
0.5 mg ranibizumab
0.5 mg ranibizumab 0.5 mg ranibizumab PRN versus
PRN extension trial monthly versus dexamethasone
PRN*

*After 7 monthly ranibizumab injections

1. Campochiaro PA, et al. Ophthalmology 2010;117:1102-12;
2. Heier JS, et al. Ophthalmology 2012;119:802-9;
3. Campochiaro PA, et al. Ophthalmology 2014;121:209-19;
4. Campochiaro PA, et al. Ophthalmology 2014; 1212432-42;
5. Monés J, ESASO November 2014;
6. Hattenbach L-O. World Ophthalmology Congress, Japan, 2014
Ranibizumab Studies - CRVO

CRUISE1

RETAIN3 CRYSTAL5
Extension of CRUISE
Ranibizumab 0.3 mg and HORIZON Ranibizumab 0.5 mg
and 0.5 mg versus PRN
sham ranibizumab 0.5 mg
PRN

2010 2011 2012 2013 2014 2016

HORIZON2 COMRADE-C6
SHORE4
Extension of CRUISE Ranibizumab 0.5 mg
Ranibizumab 0.5 PRN
Ranibizumab 0.5 mg mg monthly versus versus dexamethasone
PRN PRN*

*After 7 monthly ranibizumab injections

1. Campochiaro PA, et al. Ophthalmology 2011;118:2041–9

2. Heier JS, et al. Ophthalmology 2012;119:802–9
3. Campochiaro PA, et al. Ophthalmology 2014;121:209–19
4. Campochiaro PA, et al. Ophthalmology 2014;121:2432–42
5. www.clinicaltrials.gov/ct2/show/NCT01535261
6. www.clinicaltrials.gov/ct2/show/NCT01396083
 Aflibercept

 VIBRANT
 COPERNICUS
 GALILEO
Medication Treatment of RVO

 Choices of drurgs
 Steroid  IOP
 Anti VEGF
 FDA Approval for RVO ME  Ranibizumab (2010)
 Bevacizumab  off label
 Aflibercept  in progress
 As soon as possible
 Loading dose is needed
 Monitoring treatment, drug side effects
 Radial Optic Neurotomy

 Pathogenesis
 The scleral outlet may also a role in the pathogenesis
of CRVO
 Compartment syndromes : neurovascular
compression within a confined space resulting in
tissue ischemia and dysfunction
 Anatomic “bottleneck” at the scleral outlet may
impose a constriction and play a mechanical role in the
pathoetiology of CRVO

Opremcak EM. Radial optic neurotomy for central vein occlusion: pro surgery. Abstracts of 2003 AAO Subspecialty Day. Nov. 14-15, 2003;
Anaheim, CA.

 

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