Fluorescein angiography

To help verify the diagnosis and evaluate for complications, FA should be obtained to delineate the retinal vascular characteristics that may have prognostic significance: macular leakage and edema, macular ischemia, and large segments of capillary nonperfusion that may portend eventual neovascularization. FA is the only technique that will accurately define the capillary abnormalities in BRVO; it is therefore particularly important that high-quality angiography be obtained (Fig. 53.3).

Fig. 53.3 Fluorescein angiogram of branch retinal vein occlusion. (A) Blocked fluorescence from intraretinal hemorrhage is common in acute branch retinal vein occlusion. Note the telangiectatic vessels forming collaterals across the horizontal raphe. The hemorrhages obscure underlying areas of capillary nonperfusion and edema. (B) Six months later, the hemorrhages have cleared, revealing small patches of nonperfusion and macular edema.

The characteristic finding on FA is delayed filling of the occluded retinal vein. Varying amounts of capillary nonperfusion, blockage from intraretinal hemorrhages, microaneurysms, telangiectatic collateral vessels, and dye extravasation from macular edema or retinal neovascularization are other features encountered. In chronic cases, when the hemorrhages have resolved, microvascular changes on FA may provide the only clues of a previous BRVO.

When FA demonstrates macular leakage and edema with cystoid involvement of the fovea, but no capillary nonperfusion, it is presumed that the macular edema is the cause of vision loss. Under these circumstances, about one-third of patients will spontaneously regain some vision. However, patients who have had decreased vision for over 1 year as a result of macular edema are much less likely to regain vision spontaneously. When macular edema is present ophthalmoscopically within the first 6 months after a BRVO and there is little or no leakage on FA, macular ischemia may be the cause of the macular edema. In such circumstances, the edema almost always spontaneously resorbs in the first year after the occlusion, often with return of vision.²⁷

Unfortunately, acute BRVOs with dense intraretinal hemorrhages may make FA interpretation challenging due to blockage of fluorescence by the hemorrhages. Thus, it is advisable to obtain FA only after the intraretinal hemorrhages have cleared significantly from the macula. Other diagnostic tests, such as OCT, can be obtained in the acute phase to aid in the diagnosis of macular edema.

Wide-field angiography

Wide-field angiography is not a commonly used imaging modality for patients with BRVO, but a recent study supports its utility. Ultrawide-field FA using the Optos C200MA revealed a correlation between nonperfusion in the peripheral retina with macular edema and retinal neovascularization.²⁸ Future studies to determine if laser photocoagulation of the nonperfused peripheral retina decreases macular edema and neovascularization may alter the therapeutic paradigm. In patients with recalcitrant macular edema or retinal neovascularization, wide-field angiography may reveal peripheral areas of nonperfusion helping to guide targeted laser photocoagulation.

Optical coherence tomography

OCT has arguably become the most important imaging modality in the treatment of patients with BRVO and macular edema. OCT offers a noninvasive and rapid method of quantitatively measuring macular edema. OCT is frequently used to monitor the response to treatment of macular edema and has been used in place of FA in some treatment trials for BRVO. Unlike FA, intraretinal hemorrhages have a minimal effect on the interpretation of OCT, making this imaging modality helpful, even in the acute setting with foveal hemorrhage. The characteristic findings of BRVO on OCT are cystoid edema, intraretinal hyperreflectivity from hemorrhages, shadowing from edema and hemorrhages, and occasionally subretinal fluid^29,30 (Fig. 53.4A). In chronic cases, photoreceptor inner-segment–outer-segment junction abnormalities from long-standing macular ischemia and macular edema may also be seen (Fig. 53.4B).

Fig. 53.4 Spectral-domain optical coherence tomography of an eye with a branch retinal vein occlusion (BRVO). (A) Raster scan of the BRVO in Figure 53.1 reveals cystoid macular edema, intraretinal fluid, and shadowing (between the arrowheads). Intraretinal heme (arrow) appears hyperreflective and produces a shadow on optical coherence tomography. (B) Raster scan of a chronic BRVO with inner-segment–outer-segment abnormalities and a large cyst.

Young patient

BRVO typically occurs in patients beyond their sixth decade of life. When they present in younger patients, an underlying predisposing condition may be suspected. In this younger patient population, a detailed history should be taken, including the use of oral contraception in females, or the use of other medications that can promote a hypercoagulable state or thromboembolism. Workup should be performed in consultation with an internist. Systemic blood pressure should be checked and the patient should be screened for diabetes. In suspected cases, infectious causes such as Lyme disease, syphilis, or human immunodeficiency virus should be screened. In young patients with other systemic findings suggestive of inflammatory disease or coagulopathy, workup should include a complete blood count, prothrombin time/partial thromboplastin time/international normalized ratio, lipid panel, serum homocysteine, anticardiolipin antibodies, antinuclear antibodies with lupus anticoagulant, protein C/S, and activated protein C resistance (factor V Leiden).^10,11,31

In young patients without systemic symptoms suggestive of a coagulopathy, careful consideration should be given in consultation with an internist prior to initiating an exhaustive systemic workup unless a vision-disabling complication has occurred. It is unclear whether the risks involved with lifelong anticoagulation are justified.

Older patient

In patients older than 60, additional workup is not necessary since the majority of these cases are idiopathic or due to hypertension or atherosclerosis.

Bilateral or numerous BRVO patients

In bilateral cases or in cases with a history of multiple BRVOs, searching for an infectious or inflammatory disorder or hypercoagulopathy may be warranted. There are numerous case reports of patients with bilateral vein occlusions and systemic inflammatory disorders or hypercoagulopathies; however the vast majority can be attributed to systemic hypertension.^32–37 The workup should proceed in the manner described for young patients.

Branch Vein Occlusion Study for macular edema

The collaborative Branch Vein Occlusion Study (BVOS),³⁸ a multicenter randomized clinical trial supported by the National Eye Institute, reported that argon laser photocoagulation may reduce visual loss from macular edema for those eyes that meet study eligibility criteria and are treated according to that protocol. Important eligibility criteria included fluorescein-proven perfused macular edema involving the foveal center, absorption of intraretinal hemorrhage from the foveal center, recent BRVO (usually 3–18 months’ duration), no diabetic retinopathy, and vision reduced to 20/40 or worse after best refraction.

In the BVOS,³⁸ argon laser photocoagulation was applied in a grid pattern throughout the leaking area demonstrated by FA (Fig. 53.5). Coagulation extended no closer to the fovea than the edge of the capillary-free zone and no further into the periphery than the major vascular arcade. Recommended treatment parameters included a duration of 0.1 second, a 100-µm diameter spot size, and a power setting sufficient to produce a “medium” white burn. FA was repeated 2–4 months after the treatment, and additional photocoagulation was applied to residual areas of leakage if reduced visual acuity persisted. Improvement in visual acuity was assessed in several ways.³⁸ When improvement was defined as reading two or more Snellen lines (beyond baseline) at two consecutive visits, treated eyes showed visual improvement more often than untreated eyes. After 3 years of follow-up, 63% of treated eyes gained two or more lines of vision, compared to 36% of untreated eyes. The average gain in visual acuity for treated eyes was one more Snellen line than in untreated eyes.

Fig. 53.5 Grid macular laser for macular edema. (A) Fluorescein angiogram, late phase, demonstrating macular edema with foveal involvement. (B) Immediate posttreatment fundus photograph showing grid pattern of laser photocoagulation.

Before laser photocoagulation is performed, it is important to obtain high-quality FAs of the macula; the FA must demonstrate that the macular edema involves the center of the fovea and that there is not a large amount of capillary nonperfusion adjacent to the capillary-free zone that could explain the visual loss. In addition, it is important to follow patients for a length of time sufficient to ascertain that macular edema is not resolving spontaneously. During this period of follow-up, it should be demonstrated that there is clearing of intraretinal hemorrhage and that there is no hemorrhage in the center of the fovea that could account for a spontaneously reversible cause of visual loss. In the application of the grid photocoagulation, laser absorption occurs at the level of the pigment epithelium; photocoagulation is not applied to close the leaking and dilated capillary vasculature directly and immediately. Although it is not understood how the laser treatment may act in lessening edema, it is interesting to note that preliminary experimental studies in the normal primate have shown a decrease in capillary diameter when this form of therapy is used and when laser absorption occurs at the level of the pigment epithelium.³⁹ One explanation for the effect of grid pattern photocoagulation is that it results in a thinning of the retina (in particular the outer retina), reducing oxygen consumption and increasing choroidal delivery of oxygen to the inner retina, producing a consequent autoregulatory constriction of the retinal vasculature in the leaking area and thereby decreasing the edema.

In the application of grid pattern laser photocoagulation, it is crucial to obtain good definition of landmarks so that the center of the fovea can be identified and avoided. Since landmarks frequently may be obscured in the macula after BRVO, such cases can be managed more effectively and safely by treating well peripheral to the capillary-free zone in the first sitting. When the patient returns in 2 months for follow-up evaluation, a repeat FA may identify more clearly the amount of further treatment that needs to be applied closer to the edge of the capillary-free zone, because the pigmentation of the previous treatment is then visible. Consequently, treatment in this next sitting may be advanced closer to the edge of the capillary-free zone, if that is deemed necessary because of persistent foveal edema and vision loss. The placement of grid laser treatment in this repetitively staged fashion may be safer and appears to be just as effective as a single treatment. It has never been established that macular edema must be treated quickly or that long-standing edema produces irreversible macular damage in the first 2–3 years.

For the grid treatment used in the BVOS, the argon blue-green wavelength was employed.³⁸ This is the only wavelength that has been proven effective and it is unknown whether argon green and krypton red photocoagulation are equally effective. In other diseases, when laser treatment is applied inside the capillary-free zone, it is recognized that krypton red and argon green laser photocoagulation are absorbed less than blue-green by the xanthophyll pigment of the inner retina that is present in increasing concentrations close to the foveal center. However, because the grid treatment never comes closer to the fovea than the capillary-free zone, the BVOS did not encounter any problems with the argon blue-green laser in this region; consequently, this laser continues to be recommended.

The summary recommendations for management of acute branch vein occlusion from the BVOS emphasize waiting at least 3–6 months before considering laser therapy. If the vision is reduced to 20/40 or worse, wait 3–6 months for sufficient clearing of retinal hemorrhage to permit high-quality FA and then evaluate for macular edema and macular ischemia. If perfused macular edema accounts for the visual loss, and vision continues to be 20/40 or worse without spontaneous improvement, consider grid macular photocoagulation. However, this conclusion needs to be balanced against the improvements in vision seen with recent anti-vascular endothelial growth factor (VEGF) agents. If macular ischemia accounts for the visual loss, no laser treatment is recommended to improve vision.