Branch Retinal Vein Occlusion (BRVO) Treatment & Management

Updated: Sep 28, 2018
  • Author: Lihteh Wu, MD; Chief Editor: Douglas R Lazzaro, MD, FAAO, FACS  more...
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Treatment

Medical Care

Medical treatment of branch retinal vein occlusion (BRVO) is not effective. In the past, anticoagulants, fibrinolytic agents, clofibrate capsules (Atromid-S), and carbogen inhalation have been used but without success.

Hemodilution has been proposed as an alternative treatment of BRVO by lowering the hematocrit and plasma viscosity and by improving retinal perfusion. However, the true benefit of hemodilution has not been established because published reports have used combination therapy in the hemodilution group.

Intravitreal Corticosteroids

Intravitreal injection of triamcinolone has been used to treat macular edema of different etiologies because of its potent antipermeability and anti-inflammatory properties. A few cases of macular edema secondary to BRVO treated with an intravitreal triamcinolone injection have been reported. The exact dose remains unclear. Doses from 4 mg to 25 mg have been reported to be effective. Multiple doses appear to be needed.

In a retrospective uncontrolled case series of 92 eyes, intravitreal injection of 4 mg of triamcinolone improved the mean best corrected visual acuity by 2.5 lines at 12 months of follow-up. It is unclear how many eyes required re-injection since this series combined eyes with central and hemiretinal vein occlusion. [21] Trans-Tenon’s retrobulbar injection of 20 mg of triamcinolone acetonide has been reported to be effective. Interestingly, it appears to be more effective in eyes with a posterior vitreous detachment. [22]

Dexamethasone is a more potent corticosteroid than triamcinolone. Furthermore, intravitreal injections of dexamethasone achieves high intravitreal drug levels without any toxic effects. The main drawback of dexamethasone is its short intraocular half life of 3 hours. A biodegradable intravitreal 0.7 mg of dexamethasone implant (Ozurdex) has been designed and approved in patients with macular edema secondary to RVO. [23]

Clinical experience has shown that the effect of a single intravitreal injection of the dexamethasone intravitreal implant lasts close to 4 months. It may be re-injected and one can expect a similar effect with the exception that the effect does not last as long as the initial injection. [24, 25]

Complications resulting from corticosteroid therapy include cataract formation, elevation of intraocular pressure, infectious endophthalmitis, noninfectious endophthalmitis, and retinal detachment. The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study compared the effects of macular laser photocoagulations with 1 mg and 4 mg of intravitreal triamcinolone in eyes with macular edema secondary to BRVO. At 12 months of follow-up, the visual acuity was similar in the 3 groups. However, the rates of elevated intraocular pressure and cataract formation were much higher in the 4-mg triamcinolone group. [26, 27]

Intravitreal Anti-VEGF

Vascular endothelial growth factor (VEGF) is a potent inductor of vascular permeability and intraocular neovascularization. In humans, the aqueous levels of VEGF and interleukin 6 (IL-6) are correlated with the degree of retinal ischemia and the severity of macular edema in BRVO. Therefore, VEGF inhibition appears to be a promising treatment modality for macular edema.

Bevacizumab is a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms. Several small retrospective and uncontrolled case series suggest that intravitreal bevacizumab at doses up to 2.5 mg are effective in improving visual acuity and reducing central macula thickness in eyes with macular edema secondary to BRVO. These results are often seen within 1 month of injection. However, most of the eyes will require additional injections to maintain the effects of bevacizumab. [28, 29, 30, 31] Other small, uncontrolled prospective studies have confirmed these initial observations. [32, 33, 34, 35, 36]

The optimum dosing and sequence for intravitreal bevacizumab in BRVO is still undetermined. The 2 most commonly used doses of bevacizumab evaluated were 1.25 mg and 2.5 mg. In a small comparative retrospective study, no differences with respect to central macular thickness, best corrected visual acuity, or total number of injections were observed between the 1.25 mg dose and the 2.5 mg dose. [37]

In a small prospective case series, 21 eyes received 3 initial intravitreal injections of 1 mg of intravitreal bevacizumab at monthly intervals and were followed for 12 months. [34] If macular edema persisted, the patient was retreated with up to 2.5 mg of bevacizumab.

In a small prospective pilot study, 1.25 mg of intravitreal bevacizumab was shown to reduce central macular thickness and improve visual acuity more efficiently than macular photocoagulation at 12 months of follow-up. [38]

A recent meta-analysis of the effect of intravitreal bevacizumab on macular edema secondary to BRVO concluded that intravitreal bevacizumab was beneficial in terms of improving visual acuity and reducing macular edema. [39]  See the images below.

Optical coherence tomography (OCT) of a patient wi Optical coherence tomography (OCT) of a patient with macular edema secondary to branch retinal vein occlusion (BRVO) prior to the initiation of anti-VEGF therapy. The visual acuity was 20/150.
Optical coherence tomography (OCT) following 3 mon Optical coherence tomography (OCT) following 3 monthly intravitreal bevacizumab injections (1.25 mg). The visual acuity improved to 20/30.

A multicenter, prospective, phase III trial (BRAVO Study) comparing intravitreal ranibizumab and sham injections demonstrated the value of VEGF inhibition in eyes with macular edema secondary to BRVO. In this study, eyes were randomized to monthly sham injections, 0.3 mg of ranibizumab and 0.5 mg of ranibizumab, for the first 6 months. Eyes were eligible for rescue laser at month 3 if the hemorrhages had sufficiently cleared to allow safe treatment and if the visual acuity remained at 20/40 or less and the central macular thickness was 250 µm or less. [40]

During months 6-12 of the study, eyes were injected as needed, and the sham group was offered 0.5 mg ranibizumab. Again at month 9, eyes that did not responding to intravitreal ranibizumab were allowed laser rescue. At 12 months, eyes gained an average of 12.1, 16.4, and 18.3 letters in the sham, 0.3 mg, and 0.5 mg groups, respectively. Similarly, central foveal thickness decreased with ranibizumab treatment. Sham eyes had gained 7.3 letters at 6 months and had an additional gain of 4.8 letters after intravitreal ranibizumab was instituted. This suggests that timing is important and eyes with macular edema secondary to BRVO should be offered VEGF inhibition upon diagnosis in order to achieve the best possible visual outcome.

During months 13 to 24 (HORIZON Trial), eyes were followed at least every 3 months and were re-injected with 0.5 mg of ranibizumab if macular edema was present. In addition, these eyes were eligible for rescue grid laser therapy if the visual acuity was less than 20/40 and macular edema was still present. A large percentage of eyes received grid macular laser rescue therapy during the first 12 months of the study in all the study arms. After 2 years of follow-up, the visual gains were maintained with continued VEGF suppression. [41]

Thirty-four eyes enrolled in the BRAVO and HORIZON Trials were followed for an average of 49 months (RETAIN Study). Half of these eyes experienced edema resolution, which was defined as an absence of intraretinal fluid for 6 months or longer since the last injection. The mean number of injections in eyes without edema resolution during year 4 of follow-up was 3.2. In eyes with resolution of edema, the mean gain of BCVA was 25.9 letters compared with 17.1 letters in eyes with unresolved edema. This difference was not statistically significant. Close to 80% of eyes obtained a BCVA of 20/40 or greater, regardless of edema resolution. [42]

A 2016 clinical trial, the BRIGHTER Study, has shown that an individualized visual acuity–based regimen of ranibizumab results in good visual acuity gains. [43]

In October 2014, the indication for aflibercept was expanded to include branch retinal vein occlusion (BRVO). The expanded indication is based on the previously approved indication for macular edema following CRVO and the positive results from the double-masked, randomized, controlled phase 3 VIBRANT study of 181 patients with macular edema following BRVO. The VIBRANT study compared intravitreal aflibercept 2 mg once every 4 weeks with macular laser photocoagulation (control).

At 24 weeks, significantly more patients treated with aflibercept gained at least 15 letters in vision (3 lines on an eye chart) from baseline as measured on the early treatment diabetic retinopathy study (ETDRS) chart, the primary endpoint of the study, compared with patients who received control (53% vs 27%; P< 0.01). Patients treated with aflibercept achieved a 17-letter mean improvement over baseline in best-corrected visual acuity (BCVA) compared to a 6.9-letter mean improvement in patients who received control (P< 0.01), a key secondary endpoint. [44]

Multiple clinical trials have shown that timing is an important prognostic factor in eyes with macular edema due to BRVO. In the past, time was given for spontaneous resolution and clearing of intraretinal hemorrhages to allow performance of a "good" fluorescein angiogram. The authors no longer recommend this waiting period. An OCT should be the first diagnostic test; and if macular edema is present, initiation of treatment should be strongly considered. [19, 23, 40]

Retinal nonperfusion is related to intravitreal VEGF levels. Progressive retinal nonperfusion may be responsible for loss of visual gains, particularly in eyes in which macular edema has not resolved and anti-VEGF injections are given sporadically. The authors from this study state that in eyes with macular edema secondary to RVO, the resolution of macular edema should not be the sole treatment objective. The prevention of worsening retinal nonperfusion should be a treatment objective as well. Periodic fluorescein angiograms, preferably wide-angle, should be performed to monitor perfusion status. [45, 46]

Combination Therapy

In a retrospective case control study, 22 eyes underwent subthreshold micropulse laser plus intravitreal ranibizumab, and 24 eyes underwent intravitreal ranibizumab monotherapy. Eyes in the ranibizumab monotherapy group received an initial injection and were then followed monthly with serial OCTs. Eyes were re-injected if macular edema recurred. Eyes in the combination arm received an initial ranibizumab injection followed by subthreshold micropulse laser treatment one month after the initial injection. Thereafter, the patients were monitored monthly and were re-injected if macular edema was observed in the OCTs. At 6 months, the visual results and the central macular thickness results were comparable in both treatment arms. The number of injections in the combination arm (1.9) were significantly fewer than the number of injections in the ranibizumab monotherapy group (2.3). [47]

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Surgical Care

Branch retinal vein occlusions (BRVOs) have a relatively benign course. Nevertheless, certain complications that lead to visual loss may occur. These complications include macular edema and the sequelae from retinal neovascularization (eg, vitreous hemorrhage, tractional retinal detachment, neovascular glaucoma). Several surgical and laser techniques are available to deal with these situations.

Macular grid laser photocoagulation

Macular grid laser photocoagulation was mildly effective in the treatment of macular edema in a small prospective trial, the BVOS.

The current recommendation is to wait 3 months to see if the patient's vision spontaneously improves.

If no improvement occurs and if the hemorrhages have mostly cleared from the macular area, a fluorescein angiogram is obtained. If the angiogram shows leakage in the macular area that is responsible for the decrease in vision, treatment with a macular grid laser is recommended. After 3 years of follow-up care, 63% of laser treated eyes improved by 2 or more lines of vision compared with 36% of control eyes. [19]

Despite macular photocoagulation, eyes gained on average 1.33 lines of vision with respect to baseline. At the 3-year follow-up, 40% of eyes had a visual acuity of less than 20/40 and 12% of eyes had a visual acuity of less than 20/200. [19]

If the fluorescein angiogram reveals macular nonperfusion, laser therapy is not warranted, and observation is recommended. Finkelstein reported that eyes with macular nonperfusion have a good visual prognosis. [48] In his series, the median visual acuity was 20/30.

Macular grid laser photocoagulation remains the criterion standard treatment of eyes with perfused macular edema secondary to BRVO.

Scatter photocoagulation

The BVOS also demonstrated that scatter photocoagulation reduces the prevalence of neovascularization from 40% to 20%.

However, if all eyes with nonperfusion were treated, 60% of patients who would never develop neovascularization would be treated.

If only the eyes that develop neovascularization were treated, the events of vitreous hemorrhage would decrease from 60% to 30%.

Therefore, the recommendation is to wait until neovascularization actually develops before scatter photocoagulation is considered.

The introduction of ultra–wide-field FA imaging has allowed the identification of vascular abnormalities in the retinal periphery.

Laser-induced chorioretinal anastomosis

Bypass of the normal retinal venous drainage channels is attempted by creating a communication between the obstructed vessel and the choroid.

Problems with this technique are the lack of reliability in creating an anastomosis (most groups report a 30-50% success rate) and its complications. Complications from the procedure include tractional retinal detachment and vitreous hemorrhage.

Vitrectomy and arteriovenous decompression

Virtually all cases of BRVO occur at arteriovenous crossings.

Because arterial compression is believed to be the major cause of this condition, some have recommended lifting the artery from the underlying vein to relieve the compression.

Several small, uncontrolled series have shown good results in improving macular edema and macular perfusion. However, others have reported a lack of efficacy of this procedure. Planning of a multicenter controlled trial is currently underway.

Other considerations

Several surgeons have reported resolution of macular edema secondary to BRVO after vitrectomy with or without peeling of the internal limiting membrane.

Vitrectomy and posterior hyaloid separation improved the visual acuity in eyes with macular edema secondary to BRVO. The addition of intravitreal triamcinolone had no additional benefit. [49]

A number of eyes may develop a transient postoperative increase in macular edema following vitrectomy. The edema resolves spontaneously and does not appear to have an effect on visual acuity. [50]

Pars plana vitrectomy techniques with or without scleral buckling may be necessary in eyes with tractional and rhegmatogenous retinal detachments.

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Consultations

Consult a vitreoretinal specialist if complications arise.

In atypical cases where a thrombophilic condition is suspected, consultation with a hematologic specialist is recommended.

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Long-Term Monitoring

After branch retinal vein occlusion (BRVO) is diagnosed, a patient must receive follow-up care to monitor the development of possible complications.

If the patient's visual acuity remains depressed, a good quality fluorescein angiogram can be obtained when most of the hemorrhages have cleared, usually by 3 months. The angiogram guides further therapy.

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