1. Does early panretinal photocoagulation (PRP) prevent iris neovascularization (INV) in eyes with ischaemic CRVO?2. Does macular grid-pattern laser photocoagulation improve visual acuity in eyes with reduced vision due to macular oedema from CRVO?3. What is the natural history of eyes with CRVO that have little or no evidence of ischaemia (less than 10 disc areas of non-perfusion)?4. Is early PRP more effective than PRP at first identification of INV in preventing further ocular morbidity due to progressive neovascular glaucoma in eyes with ischaemic CRVO ?
The study reported that "prophylactic panretinal photocoagulation does not totally prevent" development of iris/angle neovascularization Prompt regression of iris and angle neovascularization in response to panretinal photocoagulation is more likely to occur in eyes that have not been treated previously prophylactically.
Older age, male sex, and the number of risk factors (systemic vascular risk factors and glaucoma) were correlated with poorer visual outcome. In addition, 34% of eyes with initially perfused CRVO developed ischaemic CRVO during the three-year follow-up (15% converted during the first four months of followup)
“Careful observation with frequent follow-up examinations in the early months (including undilated slit-lamp examination of the iris and gonioscopy) and prompt panretinal photocoagulation of eyes in which 2’clock iris/angle neovascularization develops."
The CVOS found no significant difference in visual outcome between the treatment and observation groups at any follow-up point Although there was a definite decrease in macular edema on fluorescein angiography in the treatment group when compared to the control group, this did not translate to a direct visual improvement
1. Does early panretinal photocoagulation (PRP) prevent iris neovascularization (INV) in eyes with ischaemic CRVO? 2. Does macular grid-pattern laser photocoagulation improve visual acuity in eyes with reduced vision due to macular oedema from CRVO?3. What is the natural history of eyes with CRVO that have little or no evidence of ischaemia (less than 10 disc areas of non-perfusion)?4. Is early PRP more effective than PRP at first identification of INV in preventing further ocular morbidity due to progressive neovascular glaucoma in eyes with ischaemic CRVO ?
Branch Vein Occlusion Study To determine whether scatter argon laser photocoagulation can prevent the development of neovascularization. To determine whether peripheral scatter argon laser photocoagulation can prevent vitreous hemorrhage. To determine whether macular argon laser photocoagulation can improve visual acuity in eyes with macular oedema reducing vision to 20/40 or worse.
The results indicated that argon laser treatment improves sight significantly in patients who already have reduced vision due to a complication of BVO called macular oedema . Laser will significantly reduce the likelihood of vitreous hemorrhage.
The lack of a proven and effective therapy for macular edema secondary to CRVO, the suboptimal outcomes of grid photocoagulation treatment for macular edema secondary to BRVO, and community enthusiasm for intravitrealtriamcinolone provided strong rationale for initiating the Standard Care versus Corticosteroid for Retinal Vein Occlusion (SCORE) Study
Standard Care versus Corticosteroid for Retinal Vein Occlusion (SCORE) Study The SCORE Study, sponsored by the National Eye Institute (NEI), includes two prospective, randomized controlled clinical trials: one among patients with CRVO (the SCORE-CRVO trial) and one among patients with BRVO (the SCORE-BRVO trial).
The trials were designed (1) to determine whether intravitrealtriamcinoloneacetonide at 1-mg and 4-mg doses produces greater visual benefit, with an acceptable safety profile, than standard care for the treatment of vision loss associated with macular edema secondary to retinal vein occlusion, and (2) to compare the efficacy and safety of 1-mg and 4-mg triamcinolone doses.
The SCORE-CRVO trial demonstrated that intravitreal injections of triamcinoloneacetonide were superior to observation for vision loss associated with macular edema secondary to CRVO, and the 1 mg dose of intravitrealtriamcinolone had a safety profile superior to that of the 4 mg dose of intravitrealtriamcinolone and similar to the observation group.
In SCORE-BRVO, which included a BRVO study cohort similar to that of the BVOS, intravitreal injections of triamcinoloneacetonide was not found to be associated with improved visual acuity outcomes compared with grid photocoagulation.
Investigative Group concluded that grid photocoagulation should remain the benchmark against which other treatments are compared in clinical trials for eyes with vision loss associated with macular edema secondary to BRVO
Cruise/Bravo Study Cruise study : CRVO Bravo study : BRVO Two large-scale randomized clinical trials demonstrate that anti-VEGF therapy significantly improves vision in patients with central or branch retinal vein occlusion
Summary of all the completed studies CRVO/BRVO: Investigate for all predisposing factors If any of them are positive they should be kept under control
Summary of all the completed studies CRVO : with iris/angle neovascularisation > 2clock hrs: prompt PRPc. < 2clock hrs wait and watch with macular edema: IntravitrealTriamcinolone 1mg without macular edema : Wait and watch
BRVO: With macular edema: macular grid photocoagulation Without macular edema: wait and watch.
INTRAVITREAL THROMBOLYSIS The rationale for intravitreal administration of tissue plasminogen activator (t-PA) is that it can diffuse across the internal limiting membrane of the retina and enter the retinal circulation through capillaries damaged by Breakdown of the blood-retina barrier following CRVO. The t-PA would then be transported by residual venous flow towards the lamina cribrosa, the presumed site of thrombus, to cause thrombus lysis.
Complications of intravitrealthrombolysis include vitreous haemorrhage and an increase in macular oedema. Drawback ? .
RETINAL VEIN THROMBOLYSIS Retinal vein cannulation allows t-PA to be delivered under direct view into the retinal vein to cause thrombolysis. t-PA is injected early after onset of the vein occlusion, collateral vessels will not yet have developed and the t-PA may then reach the desired site.
0PHTHALMIC ARTERY THROMBOLYSIS To selectively catheterise the ophthalmic artery and infuse a fibrinolytic agent close to the obstruction site.
Femoral artery – internal carotd artery – ophthalmic artery….. Urokinase was then infused over 1 hour. Intravenous heparin for 48 hours, followed by subcutaneous low molecular weight heparin for 1 month (to inhibit coagulation on the thrombus and limit clot extension and recurrence) and oral aspirin for 3 months (to combat risk factors for atherosclerosis and prevent further thrombosis).
ISOVOLEMIC HAEMODILUTION In isovolemichemodilution, venesection is performed at the same time as infusion of a plasma substitute (for example, hydroxyethyl starch, dextran) so that a constant blood volume is maintained. By reducing the haematocrit level, haemodilution causes a reduction in blood viscosity and thus improves retinal blood flow and oxygen supply.
Isovolaemichaemodilution alone has not been shown to prevent neovascular glaucoma or to arrest ischaemia
RADIAL OPTIC NEUROTOMY It is thought that radial optic neurotomy releases pressure in the scleral outlet compartment (the space containing the scleral canal, cribriform plate, optic nerve, central retinal artery and vein). This increases the central retinal vein lumen which in turn increases venous flow and helps clear the thrombus.
The presence of a hypothetical bottleneck at the optic nerve head is not logical given that the difference in diameter between retrolaminar and prelaminar optic nerves could be explained by the presence of a myelin sheath. The theory would also not be able to explain the development of a hemiretinalvein occlusion. The central retinalvein lies temporal to the artery in the optic nerve, enclosed by a common fibrous capsule. Thus, the nasal cut in radial optic neurotomy cannot decompress the vein.
OPTIC NERVE SHEATH DECOMPRESSION The rationale for optic nerve sheath decompression is that optic nerve oedema results in some degree of mechanical venous compression.
Lamina Puncture This is transvitreal optic disc surgery to create a perivascular opening in the lamina cribrosa. This aims to release the postulated constriction of the central retinal vein by the surrounding connective tissue at the level of the lamina cribrosa.
Interventional Methods for BRVO Isovolemichaemodilution Vitrectomy AV crossing sheathotomy Chorioretinalanastomosis
Chorioretinal venous anastomosis Chorioretinalanastomosis allows blood to bypass the occluded vein into the choroidal circulation. By LASER or SURGERY The best results of this procedure have been found in non-ischaemic CRVO
Reasons why some eyes respond to laser by forming anastomosis while others develop a fibrovascular response are unclear. Factors that determine whether or not an anastomosis forms include patient’s age, presence of optic nerve head collaterals, the presence of an underlying choroidal vein near the treatment site, and degree of intravascular pressure elevation in the obstructed vein.
SURGERY :Pars planavitrectomy was followed by slit-like incisions through Bruch’s membrane adjacent to a major branch of a retinal vein in each quadrant. Small pieces of 5/0 madrilene suture were placed over the vein and inserted into these incision sites to maintain its patency and promote the formation of collaterals. LASER :Endolasertreatment was then performed around the incision site followed by panretinal laser photocoagulation.
BRVO - VITRECTOMY The vitreous is postulated to have a role in the pathogenesis of neovascularisation and macular oedema, which may complicate BRVO and its removal may help in the management of these sight threatening complications. An intact vitreoretinal surface provides a scaffold for neovascularisation.Thevitreous allows angiogenic factors from the ischaemic retina to diffuse into it and traction through the vitreous fibres on the Muller cells of the retina predisposes to cystoid macular oedema.
It is postulated that vitrectomy allows access of oxygenated aqueous to the inner retina, thereby improving macular oedema, reducing ischaemia, and improving vision.
BRVO –AV Crossing Sheathotomy Venous compression in BRVO may be relieved by dividing the common adventitial sheath that surrounds retinal arterioles and venules at arteriovenous (A-V) crossing points. As a combined procedure with vitrectomy/vitrectomy and injection of thrombolytic into the occluded vein.
No large scale studies Long term followup difficult Optimal timing of intervention Most promising therapy in near future : vitrectomy with intravenous thrombolysis with t-PA : In CRVO