Branch Retinal Vein Occlusion

Author: Lihteh Wu, MD, Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica

Coauthor(s): Diego Mena, Associate Surgeon, Instituto de Cirugia Ocular

Lihteh Wu, MD, is a member of the following medical societies: American Academy of Ophthalmology, and Association for Research in Vision and Ophthalmology

Editor(s): Vytautas A Pakainis, MD, Chief of Ophthalmology, Dorn Veterans Administration Medical Center, Professor of Ophthalmology, Ophthalmology, University of South Carolina School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Regional Eye Center, Affiliated With Freeman Hospital and St John's Hospital, Joplin, Missouri; and Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

INTRODUCTION

Background: Much confusion exists in the literature because central and branch retinal vein occlusions (BRVOs) often are grouped and studied together. The natural history and complication rate for each entity differ. The treatments and their results vary from one condition to the other. This article deals exclusively with BRVO. Hemiretinal vein occlusions are probably variants of central retinal vein occlusions, and as such, they are not included in this discussion.

Pathophysiology: Hypertensive, atherosclerotic, inflammatory, or thrombophilic conditions may lead to retinal endothelial vascular damage. In eyes with an anatomic predisposition, intravascular thrombus formation may occur. Eyes with arteriovenous crossings appear to be at risk for BRVO. In these eyes, the artery is anterior to the vein in most cases. The artery and the vein share a common adventitial sheath.

Arterial compression of the vein is believed to be the main cause of BRVO. Compression of the vein may lead to turbulent flow in the vein. The turbulent flow in combination with the preexisting endothelial vascular damage from the different conditions creates a local environment favorable to intravascular thrombus formation. Up to two thirds of BRVOs occur in the supertemporal quadrant. This rate may be related to the increased number of arteriovenous crossings in this quadrant with respect to the rest. In addition, nasal BRVO often are asymptomatic; therefore, patients with this type of BRVO do not seek ophthalmic evaluation.

Frequency:

  • In the US: Retinal vein occlusions (branch and central) are the second most common retinal vascular diseases after diabetic retinopathy.
  • Internationally: In a population-based study from Australia, the Blue Mountains Eye Study, the prevalence of BRVO in the population older than 48 years was 1.1%.

Race: No racial predilection for the disease is apparent.

Sex: No predilection for either sex is apparent.

Age: The patients who are affected are usually in their fifth or sixth decade of life.

CLINICAL

History:

  • The Eye Disease Case-Control Study reported the following findings:
  • Systemic hypertension is a risk factor for BRVO.
  • Diabetes mellitus and open-angle glaucoma are not risk factors for BRVO.
  • Moderate alcohol consumption reduces the risk of BRVO.
  • Patients often complain of a sudden painless decrease of vision in the affected eye.
  • Some may complain of a scotoma.

Physical:

  • In 1877, Leber first described the condition ophthalmoscopically. During the acute phase, intraretinal hemorrhages (usually flame shaped), retinal edema, and cotton-wool spots are seen in the distribution of a retinal vessel. The horizontal raphe is respected.
  • During the chronic stage, hemorrhages may be absent. Macular edema may be the only sign present. Telangiectatic vessels that extend across the horizontal raphe usually can be demonstrated angiographically.
  • In certain eyes with large areas of nonperfusion, retinal neovascularization may be seen.
  • Vitreous hemorrhage with tractional retinal detachments may ensue.
  • Further traction may create retinal breaks, creating combined rhegmatogenous and tractional retinal detachments.
  • Neovascular glaucoma and neovascularization at the disc are rare events with BRVO.

Causes:

  • Most cases of BRVO are due to idiopathic factors. Usually, patients have an anatomic predisposing factor, such as an arteriovenous crossing where the artery compresses the vein. This compression leads to clot formation and subsequent BRVO.
  • Inflammatory conditions that affect the retinal veins may cause local damage that predisposes the individual to intravascular clot formation with subsequent BRVO. Some of the inflammatory conditions reported in the literature are the following:
  • Sarcoidosis
  • Lyme disease
  • Serpiginous choroiditis
  • Thrombophilic conditions, such as the following, may also be involved:
  • Protein S deficiency
  • Protein C deficiency
  • Resistance to activated protein C (factor V Leiden)
  • Antithrombin III deficiency
  • Antiphospholipid antibody syndrome
  • Lupus erythematosus
  • Gammopathies

DIFFERENTIALS

Hypertension
Macular Edema, Diabetic
Retinopathy, Diabetic, Background
Retinopathy, Diabetic, Proliferative

WORKUP

Lab Studies:

  • The authors of the Branch Vein Occlusion Study (BVOS) has recommended against extensive testing in patients with typical BRVO.
  • Certain laboratory studies may be useful in atypical cases, ie, those in young patients, bilateral cases, or those in patients with a personal or family history for thromboembolism. Determinations of following may be helpful:
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
  • Protein C, protein S, factor V Leiden, and antithrombin III
  • Homocysteine
  • Antinuclear antibody (ANA), lupus anticoagulant, and anticardiolipin
  • Serum protein electrophoresis (SPEP) results

Imaging Studies:

  • Fluorescein angiography
  • A fluorescein angiogram is obtained as soon as the hemorrhages have cleared if the patient's vision is still depressed. The test is usually done 3 months after the event.
  • The purpose is to determine the cause of visual loss (eg, macular edema or macular ischemia). If the visual loss is secondary to macular edema, laser photocoagulation in a grid pattern may be of benefit. Conversely, if macular ischemia is responsible for the loss of vision, laser photocoagulation should not be offered to the patient.
  • Optical coherence tomography: Given its ability to measure retinal thickness in a quantitative fashion, optical coherence tomography (OCT) is a useful adjunct in the follow-up of patients with macular edema secondary to BRVO.

Histologic Findings: Histopathologic studies confirm the importance of arteriovenous crossings in the pathogenesis of this condition. Inner retinal ischemic atrophic areas have been described distal to the occlusion site. Variable degrees of arteriolar sclerosis have been reported. An intravascular fresh or recanalized thrombus is often found at the site of venous occlusion.

TREATMENT

Medical Care: Medical treatment is not effective in this condition. In the past, anticoagulants, fibrinolytic agents, clofibrate capsules (Atromid-S), and carbogen inhalation have been used but without success.

More recently, intravitreal injection of triamcinolone has gained popularity among vitreoretinal specialists. Because of its potent antipermeability and anti-inflammatory properties, intravitreal triamcinolone has recently been used to treat macular edema of different etiologies. 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 to 25 mg have been reported to be effective. Complications resulting from this treatment include cataract formation, elevation of intraocular pressure, infectious endophthalmitis, noninfectious endophthalmitis, and retinal detachment. Further study is warranted to define what role, if any, intravitreal triamcinolone has in the management of macular edema secondary to BRVO.

Surgical Care: BRVO 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 effective in the treatment of macular edema in a large prospective BVOS trial.
  • 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 improve by 2 or more lines of vision compared with 36% of control eyes.
  • 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. The median visual acuity in his series was 20/30.
  • 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.
  • 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.
  • Several surgeons have reported resolution of macular edema secondary to BRVO after vitrectomy with or without peeling of the internal limiting membrane.
  • Pars plana vitrectomy techniques with or without scleral buckling may be necessary in eyes with tractional and rhegmatogenous retinal detachments.
  • Retinal vein cannulation is an experimental technique that some have advocated. If one can safely cannulate the obstructed vessel, one can deliver clot-busting medications, such as tissue plasminogen activator, and thus improve flow in the vessel.

Consultations:

  • Consult a vitreoretinal specialist if complications arise.
  • In atypical cases where a thrombophilic condition is suspected, consultation with a hematologic specialist is recommended.

MEDICATION

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Intravitreal corticosteroids-- Have potent anti-inflammatory and antipermeability properties.

Drug NameTriamcinolone (Kenalog-40) -- Through its antipermeability properties secondary to its anti-VEGF effects, strengthens blood retinal barrier and prevents its disruption.

Adult Dose4 mg is most common dose because it is easy to aliquot and inject 0.1 cc from commercially available 40 mg/mL vial; apart from convenience of dosing, no studies support this dose over any other dose

Pediatric DoseNot established

ContraindicationsDocumented hypersensitivity; fungal, viral, and bacterial skin infections

InteractionsNone reported

PregnancyC - Safety for use during pregnancy has not been established.

PrecautionsComplications include progression of nuclear sclerosis, increased intraocular pressure, retinal detachments, sterile endophthalmitis, and infective endophthalmitis; after 4-6 wk of topical corticosteroid use, 5% of eyes develop elevated intraocular pressure >16 mm Hg, and 30% develop intraocular pressure elevation of 6-15 mm Hg; unclear how long it takes for intraocular pressure to rise following initial intravitreal injection; unknown what effect initial dose, frequency of reinjection, or cumulative corticosteroid dose has on intraocular pressure; all reported studies show that 4-mg dose and 25-mg dose appear to have similar effect on intraocular pressure; most treated eyes respond to topical antiglaucoma medication but few may require filtering procedures; cataract formation appears to be associated with rise in intraocular pressure (most cataracts develop slowly; posterior subcapsular cataracts appear to be more common); to avoid endophthalmitis, use one vial per eye and sterile technique (endophthalmitis occurs in approximately 0.1% of injections)

FOLLOW-UP

Further Outpatient Care:

  • After the condition is diagnosed, a patient must receive follow-up care to monitor the development of possible complications.
  • If 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.

Complications:

  • Macular edema
  • Retinal neovascularization
  • Vitreous hemorrhage
  • Tractional retinal detachment
  • Rubeosis iridis
  • Epiretinal membrane

Prognosis:

  • An analysis of several series indicates that 53% of eyes obtain 20/40 or better visual acuity, 25% have a visual acuity between 20/50 and 20/100, and 22% have a visual acuity of 20/200 or worse.
  • The more distal the occlusion is from the optic disc, the better the visual prognosis.

Patient Education:

  • Instruct patients with BRVO to seek attention if further visual loss occurs during follow-up.

MISCELLANEOUS

Medical/Legal Pitfalls:

  • Early recognition may reduce sequelae.