In many ways, phenotypically if not genotypically, retinal venous occlusive disease shares certain features with diabetic retinopathy and is the second most common cause of macular edema.1 In terms of prevalence, it is a major public health problem, with about 130,000 cases per year in the United States, and more than twice as many in other industrialized nations.2

ROLE OF THROMBOSIS
The traditional teaching is that venous thrombosis is the cause of retinal venous occlusion, and there is support for this statement from histopathologic studies as well as intuitively.3 It is thought that the endothelium becomes damaged in response to hemodynamic stress. When the collagen under the endothelium is exposed, platelets adhere, and thrombi form, occluding the lumen.

What is also clear but has not been as well appreciated until the last 4 or 5 years, is that inflammation may play a role in the etiology. Chan, Green, and colleagues showed that in 29 eyes, inflammatory cells were adjacent to the thrombus in about 48% of the cases.4

In terms of the natural history, the severity of the occlusion and the presenting visual acuity typically determine final vision. The principal complications of branch retinal vein occlusion (BRVO) are macular edema, retinal capillary loss, and neovascularization. Although iris neovascularization rarely occurs with BRVO, it is common in central retinal vein occlusion (CRVO).

When evaluating the natural history of CRVO, it is important to pay attention to presenting visual acuity. Patients who present with 20/40 or better vision at their initial visit tend to do well. About two-thirds or more will retain 20/40 or better, whereas only a small fraction of patients who present with poor vision, 20/200 or worse, have a good outcome.5 So it behooves us to be aggressive with patients who present with poor vision and to be cautious with those who present with good vision.

EVOLUTION OF THERAPIES
Previously, therapies focused solely on complications, principally macular edema and neovascularization. Newer therapies now focus on the primary process of the occlusion or the inflammation. Some of the seminal studies on BRVO from the 1980s showed that laser photocoagulation was an effective form of therapy.6 Patients who had grid laser for macular edema were about twice as likely to achieve two lines of vision improvement and twice as likely to achieve 20/40 or better vision as those who received no treatment. Obviously, this study did not look at macular edema treated by steroids, because that treatment did not exist at that time.

A significant complication of BRVO is the development of retinal neovascularization or vitreous hemor-rhage. Patients who had neovascularization and then received laser therapy had a reduced chance of bleeding compared to the control patients.7

Interestingly, using the laser, you could reduce by half the number of patients who went on to develop neovascularization or vitreous hemorrhage, although this did not result in a difference in the final visual acuity. Although laser was not recommended in the comment section of that article, many clinicians apply laser when retinal neovascularization develops to reduce the chance of vitreous hemorrhage.8

Figure 1 shows a young patient whom I treated. You can see bleeding from an area of neovascularization. We applied scatter laser photocoagulation to areas of capillary nonperfusion, and the hemorrhage resolved, the neovascularization regressed, and patient had good visual acuity.

The Central Retinal Vein Occlusion Study (CVOS) Group found average visual acuity stayed about the same in the laser group pre- and post-treatment, as it did in the control group.9 There was no visual benefit, even though the macular edema did improve on fluorescein angiography. This is one of the first studies that showed a fundamental disconnect between vision and related surrogate measures, such as fluorescein angiographic macular edema or OCT thickness.

ANOMALIES EXIST
Whenever you mine old, well-done studies, such as the CVOS, you may find data anomalies. One might assume intuitively that if laser works well for iris neovascularization, it would work even better if you treated earlier. This was not the case. Eyes that had more than a certain amount of capillary nonperfusion on fluorescein angiography and treated with scatter photocoagulation had less iris or angle neovascularization than eyes not treated with scatter laser. However, scatter laser did not reduce the risk of neovascular glaucoma in these eyes compared with eyes receiving scatter laser after iris or angle neovascularization developed.10 As a result, the conventional wisdom and the standard of care based on this large trial is that we should not treat ischemic CRVOs without iris neovascularization with scatter photocoagulation.

CONCLUSION
Retinal vein occlusion remains a common cause of vision loss and macular edema that may benefit from laser photocoagulation in addition to newer pharmacotherapies. ■

1. Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol. 1997;115:486-491.
2. Klein R, Klein BE, Moss SE. Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 2008;98:133-141.
3. Klein BA. Occlusion of the central retinal vein; clinical importance of certain histopathologic observations. Am J Ophthalmol. 1953;36:316-324.
4. Green WR, Chan CC, Hutchins GM, Terry JM. Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Trans Am Ophthalmol Soc. 1981;79:371-422.
5. Central Vein Occlusion Study Group. Central vein occlusion study of photocoagulation therapy: baseline findings. Online J Curr Clin Trials. 1993;Oct 14:doc No. 95.
6. Finkelstein D. Argon laser photocoagulation for macular edema in branch vein occlusion. Ophthalmology. 1986; 93:975-977.
7. Branch Vein Occlusion Study Group: Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion: a randomized clinical trial. Arch Ophthalmol. 1986; 104:34-41.
8. Jain A, Blumenkranz MS, Paulus Y, et al. Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol. 2008;126:78-85.
9. The Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. M report. Ophthalmology. 1995;102:1425-1433.
10. The Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. N report. Ophthalmology. 1995; 102:1434-1444.