Fig. 15.4 Fundus images of a 54-year-old hypertensive man with an ischemic HCRVO and ME of the left eye. The VA was 20/125. He underwent radial optic neurotomy, with improvement in ME, but no improvement in VA. (a) Baseline color fundus photograph showing intraretinal hemorrhages and many cotton wool spots in the inferior hemiretina. (b) One month after radial optic neurotomy, the ME has decreased clinically, and the cotton wool spots may

be smaller, but the VA has not improved. The black arrow denotes the scar from the radial optic neurotomy. (c) Frame from the mid-phase FA shows that the venous return is still delayed in the inferior hemiretina (compare the blue arrow to the green arrow). The radial optic neurotomy scar is hypofluorescent (red arrow). Capillary nonperfusion is evident (the yellow oval)

anti-VEGF therapy, the enthusiasm for RON in the treatment of RON has waned.

15.2.4Retinal Endovascular Surgery with Intravenous Injection of Tissue Plasminogen Activator

Retinal endovascular surgery (REVS) involves pars plana vitrectomy followed by piercing of a branch retinal vein near the optic disc with an angled glass microcannula and injection of at least 1–5 ml of recombinant TPA, 200 mg/ml.61

The goal of the therapy is to displace and lyse thrombus in the central retinal vein. In a series of 28 patients with either nonischemic or ischemic CRVO treated in this fashion, 54% achieved at least three lines of VA improvement at 3 months follow-up. Vitreous hemorrhage occurred after surgery in seven patients (25%).62 Whether the rate of complications makes this approach unjustified has been a matter of controversy.24,60 When applied to eyes with ischemic CRVO, all of which had failed to improve with previous isovolemic hemodilution, VA did not improve at 1 year follow-up, arteriovenous transit time did not improve, the rate of development of

neovascular glaucoma was not reduced compared to historical control series, and the number of additional surgical procedures required was high.14 Small series have suggested that the technique can reduce macular thickening and improve BCVA, but prospective, randomized, controlled clinical trials comparing the treatment to the natural history of the disease are lacking. Color flow mapping with spectral Doppler ultrasound of three patients undergoing REVS with TPA injection did not show improvement in central venous blood flow.10 It is hypothesized that the poor results with this method reflect inability of mechanical flushing to dislodge the clot and inability of the TPA as given to dissolve the thrombus.14

One criticism of the previously published technique of endovascular thrombolysis is that it relies on bolus injection of TPA. Elsewhere in the body, the minimum time needed for thrombolysis to occur is 30 min.54 To overcome these criticisms, instruments have been developed and tested in a dog model of retinal vein occlusion that allow prolonged infusion of TPA for thrombolysis.54 These techniques have not been used in human CRVO to date. Another criticism is that endovascular TPE will most likely bypass the central retinal vein thrombus as it travels around it via collateral vessels.

15.2.5Intravitreal Injection of Tissue Plasminogen Activator

Tissue plasminogen activator has been injected intravitreally for CRVO on the assumption that it diffuses across the internal limiting membrane and crosses the disrupted blood – retina barrier to enter the retinal venous circulation in concentrations sufficient to speed lysis of a thrombus in the CRV.49 IVI of tissue plasminogen activator in dosages of 50–110 mg has been used in an attempt to lyse the central venous thrombus with variable anecdotal success but no control groups allowing a valid estimation of efficacy.19,20,33,49 In a rabbit model, TPA half-life

in the vitreous cavity was 4–6 h without a fibrin clot and 10–12 h in the presence of a fibrin clot.29 Uncontrolled case series have led to anecdotal impressions of greater improvement than expected from natural history, but the technique is not widely used, nor are controlled clinical trials being conducted to test the efficacy of this treatment approach. A rat model of CRVO suggested that intravitreal TPA toxicity is exacerbated in the presence of ischemia.65 Because of case reports of pigmentary changes of the retinal pigment epithelium, serous retinal detachment, and reduced ERG amplitudes after injection of 100 mg of intravitreal TPA and after two injections of 50 mg of TPA, it was suggested that doses of less than 50 mg be used in future attempts to treat CRVO by this technique.65 A hypothetical difficulty with this treatment is the variable maturity of clots at the time of presentation. Tissue plasminogen activator is most effective for fresh thrombus.35

Bleeding is the major side effect of TPA, but in the doses used in the eye, systemic bleeding is not a problem.36 Intraocular hemorrhage can be a problem, however, as can an increase in ME associated with its use.19,20,33,49

15.2.6Intravitreal Tissue Plasminogen Activator and Triamcinolone

In a pilot interventional case series of 20 patients with CRVO and ME naïve to IVIs, a mixture of triamcinolone 4 mg and TPA 25 micrograms was injected intravitreally.66 Reinjections were given at follow-up visits if macular thickness exceeded 400 m. Best corrected VA improved ³3 lines at 1, 3, 6, and 12 months in 65%, 55%, 55%, and 53%, respectively. Mean OCT measured macular thickness decreased from 1,072 to 455, 450, 480, and 409 m, respectively. The patients received a mean of 2.5 ± SD 1.1 injections over 12 months of fol- low-up. Intraocular pressure rose in 20% and cataracts worsened in 15% of eyes. A randomized clinical trial would be needed to be able to

assess clinical efficacy of this technique, but it has not been done.66

15.2.7Systemic Acetazolamide for Central Retinal Vein Occlusion with ME

mean follow-up of 12.4 months was reported, but in the absence of a control group, such a small number of cases reported, and given the invasiveness of the surgical procedure, there has been little enthusiasm to explore this treatment approach further.

Sporadic success has been claimed for this therapy at the price of a high rate of systemic side effects.26 This treatment has not been tested in a controlled trial and is little used.26

15.2.8Combined Central Retinal Vein Occlusion and Central Retinal Artery Occlusion

For eyes with a combined central retinal artery occlusion and CRVO, intra-arterial urokinase infused into the ostia of the ophthalmic artery for 1 h followed by intravenous heparin for 48 h has been suggested to be effective in an uncontrolled case series.44,57,58 No controlled studies have been done to test whether this modality is efficacious. In addition to no proof of efficacy, vitreous hemorrhage and recurrence of CRVO after heparin is stopped and a need to begin treatment soon after symptoms develop are disadvantages of this treatment.49

15.2.9Optic Nerve Sheath Decompression

On the assumption that reduction in optic disc edema could reduce venous compression at the level of the optic disc, optic nerve sheath decompression has been attempted in an uncontrolled case series as a treatment for worsening CRVO with optic disc edema.12 VA improvement at a

15.2.10Section of the Posterior Scleral Ring

An external ocular operation consisting of sectioning the posterior scleral ring to decompress the central retinal vein was attempted in 44 patients with CRVO in an uncontrolled case series.2 Forty eight percent of eyes had unchanged VA, 39% had an improved VA, and 14% a decrease in VA. The study was uncontrolled, the length of follow-up was not given, and the definitions of improved and decreased visual outcome were not given.2 Given these shortcomings and the invasiveness of the procedure, it has not been adopted.

15.2.11Infusion of High Molecular Weight Dextran

Inpatient infusion of high molecular weight dextran has been given for CRVO under the assumption that it might be beneficial by reducing erythrocytic aggregation, reducing whole blood viscosity, osmotically drawing extracellular fluid back into the vessels (edema reduction), and reducing thrombus propoagation.46 In the short term, nine cases of CRVO had improved vision and two cases were unchanged. No adverse side effects were noted.46 The study was uncontrolled, the length of follow-up was not given, and the definitions of improved and unchanged visual outcome were not given.46 Given these shortcomings, and the requirement for inpatient treatment, it has not been adopted.