Retinal Vein Occlusion
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Disease Entity
Vascular Occlusions
Disease
Retinal vein occlusion (Branch Retinal Vein Occlusion (BRVO), Central Retinal Vein Occlusion (CRVO)) are vascular occlusions of either the branch or central retinal vein resulting in potential vision changes and long term sequelae.
Etiology
Both CRVO and BRVO are related to occlusion of the retinal vein, however the cause of the occlusion differs based on location.
- Central Retinal Vein Occlusion (CRVO) occurs when a thrombus occludes the central retinal vein near the lamina cribrosa (Green, 1981)[1]
- Branch Retinal Vein Occlusion (BRVO) occurs when a thrombus occurs at the arteriovenous crossing point secondary to atherosclerosis of the retinal artery causing compression of the retinal vein. (Frangieh, 1982)[2]
Risk Factors
Despite similarities, the risk factors differ between CRVO and BRVO.
CRVO (The Eye Disease Case-Control Study Group, 1996)[3]
- Hypertension
- Open angle glaucoma
- Diabetes mellitus
BRVO (The Eye Disease Case-Control Study Group, 1993)[4]
- Hypertension
- Cardiovascular disease
- Open angle glaucoma
- High body mass index (not diabetes mellitus)
General Pathology
Please see the specific EyeWiki Articles [Central Retinal Vein Occlusion (CRVO), Branch Retinal Vein Occlusion (BRVO)] for more details.
- CRVO – A thrombus forms at the central retinal vein near the lamina cribrosa (Green, 1981)[1]
- BRVO – Arterial compression of the vein at the arteriovenous crossing causes turbulence which may lead to endothelial cell damage and thrombus formation (Frangieh, 1982)[2]
Pathophysiology
Retinal vein occlusions can cause macular edema, retinal ischemia, neovascular complications such as glaucoma, vitreous hemorrhage and retinal traction.
Primary prevention
Optimal management of associated risk factors.
Diagnosis
Diagnosis is based upon the retinal examination findings of intraretinal hemorrhages, dilated veins, and often cotton wool spots that has been described as a "blood and thunder appearance" for CRVO. Macular edema may also be present.
History
Patients often present with acute vision loss. They may have a history of cardiovascular disease, diabetes mellitus and/or hypertension.
Physical examination
Clinicians should consider performing an undilated slit lamp anterior segment examination with gonioscopy to look for neovascularization of the angle prior to a dilated fundus examination with ophthalmoscopy. In addition, fluorescein angiography and optical coherence tomography (OCT) may supplement clinical decision making. Fluorescein angiography is useful for determining the degree of ischemia present. OCT is useful for monitoring macular edema.
Signs
Retinal vein occlusions demonstrate variable degrees of intraretinal hemorrhage, cotton wool spots, macular edema, subretinal fluid, collateral vessels (chronic), iris and retinal neovascularization, dilated and tortuous veins, and sclerotic vessels with atrophy when chronic.
Symptoms
Common: Central or peripheral monocular vision loss. Less common: Transient visual obscurations or asymptomatic
Clinical diagnosis
Since the differential diagnosis is limited, retinal vein occlusions are often diagnosed with history and physical examination alone.
Diagnostic procedures
Fluorescein angiography may be used to determine the degree of retinal ischemia and diagnose macular edema. This may be important for prognostic reasons and to predict the development of neovascular sequelae. Optical coherence tomography may be used to diagnose macular edema and gauge response to treatment.
Laboratory test
In older patients with cardiovascular risk factors, no laboratory tests are needed. In atypical cases such as younger patients and bilateral or recurrent retinal vein occlusions, laboratory tests such as a complete blood count, blood pressure, fasting serum glucose, serum protein electrophoresis, homocysteine, serum viscosity, and thrombophilic screening (factor V Leiden mutation, protein C or S deficiency, antithrombin III deficiency, antiphospholipid antibodies) may be considered. Electrolytes, urea and creatinine may be obtained to rule out renal hypertension. Thyroid profile may also be helpful as thyroid disease occurs with a higher prevalence in retinal vein occlusion patients. ECG to rule out left ventricular hypertrophy.
Special tests
- Carotid duplex to rule out ocular ischemic syndrome
- Chest X-ray- tuberculosis, sarcoidosis, left ventricular hypertrophy
- Serum ACE - sarcoidosis
- Treponemal serology- syphillis
- C Reactive protein
- Thrombophilia screening
Differential diagnosis
- Ocular ischemic syndrome
- Diabetic retinopathy
- Human immunodeficiency virus (HIV) retinopathy
- Hypertensive retinopathy
- Retinopathy related to blood dyscrasias
Management
General treatment
No treatment is available to reverse retinal vein occlusions. However, the iris/retinal neovascularization or macular edema may be managed with anti-vascular endothelial growth factor (VEGF) or corticosteroid injections. Macular edema in BRVO may also be managed with grid laser photocoagulation. Please refer to the EyeWiki BRVO and CRVO pages for detailed discussions of treatment options.
Medical therapy
Medical therapy can limit complications from retinal vein occlusions. Anti-VEGF intraocular injections can induce regression of iris neovascularization (Ciftci, 2009)[5] and decrease macular edema (Spaide, 2009; Kondo, 2009)[6][7]. In addition, the SCORE study demonstrated the benefit of triamcinolone acetonide for macular edema secondary to central retinal vein occlusions (vs. sham) (Ip, 2009)[8] but did not demonstrate benefit for branch retinal vein occlusions (vs. focal laser) (Scott, 2009)[9].
The first-line therapy for macular edema with either CRVO or BRVO is currently anti-VEGF injections . Both ranibizumab (BRAVO and CRUISE)[10][11][12][13] and aflibercept (GALILEO/COPERNICUS; VIBRANT) [14][15][16] have been shown to be efficacious in the treatment of macular edema. Significant gains in visual acuity have been demonstrated along with improvement in macular edema with therapy. Both drugs are recommended to be used monthly for the first 6 treatments and then as needed. Bevacizumab is also used off-label to treat macular edema and neovascularization in CRVO and BRVO.
Steroid implants, such as the dexamethasone implant (OZURDEX) [17] have also been FDA-approved to treat macular edema in CRVO and BRVO. It is generally used as a second-line therapy or for eyes with chronic edema that is poorly responsive to anti-VEGF injections.
The SCORE2 Study compared aflibercept with bevacizumab for macular edema due to CRVO using a non-inferiority trial design. The primary endpoint was at 6 months. Bevacizumab was non-inferior to aflibercept with respect to visual acuity and OCT thickness. [18] After 6 months, good responders were divided into monthly and treat and extend (TAE) regimens using the original assigned drugs. No significant difference was seen between monthly and TAE for each drug. There were fewer treatments given for the TAE arms as compared to monthly. [19] Poor responders at 6 months were assigned a different treatment: aflibercept eyes were assigned to dexamethasone implant and bevacizumab eyes were assigned to aflibercept. The numbers of poor responders were too small in both groups to make a definitive recommendation. However, visual acuity improved in both groups after switching.
Medical follow up
Ischemic retinal vein occlusions can cause iris or retinal neovascularization in addition to macular edema and should be monitored with an undilated iris and angle examination followed by a dilated fundus examination on a periodic basis. CRVO eyes should be examined monthly for 6 months. The risk is highest for development of rubeosis within the first 90 days and decreases through 6 months. This risk may be delayed if the patient is receiving anti-VEGF injections. Therefore, patients with ischemic retinal vein occlusions who later discontinue anti-VEGF therapy need to be watched closely. In general, fluorescein angiography should be delayed until retinal hemorrhages clear to allow for good visualization of the choriocapillaris.
Laser Surgery
The Central Retinal Vein Occlusion Study supported panretinal photocoagulation for iris neovascularization after it occurs. (CVO Study Group N Report, 1995)[20] It did not support grid photocoagulation for macular edema. (CVO Study Group M Report, 1995)[21] The Branch Vein Occlusion Study supported the use of grid laser photocoagulation of edematous area. (BVO Study Group, 1984)[22] In addition, The BVO Study Group recommended sectoral panretinal photocoagulation for the development of retinal neovascularization. (BVO Study Group, 1986)[23]
Surgical follow up
Complications
Complications associated with intravitreal injections include infection, hemorrhage, retinal detachment, cataract, and both infectious and sterile uveitis; however, these complications remain relatively rare. Triamcinolone acetonide and dexamethasone implant can also cause a steroid-induced glaucoma.
Prognosis
The prognosis is highly variable depending on the location of the retinal vein occlusion, degree of ischemia, and development of sequelae. Please see EyeWiki BRVO and CRVO pages for more in depth information.
Additional Resources
- Boyd K, Vemulakonda GA. Branch Retinal Vein Occlusion (BRVO). American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/branch-retinal-vein-occlusion-brvo-list. Accessed January 06, 2023.
- Gregori NZ, Vemulakonda GA. Central Retinal Vein Occlusion. American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/diseases/central-retinal-vein-occlusion-list. Accessed January 06, 2023.
- Porter D, Vemulakonda GA. Blood Pressure. American Academy of Ophthalmology. EyeSmart/Eye health. https://www.aao.org/eye-health/anatomy/blood-pressure-list. Accessed January 06, 2023.
References
- ↑ 1.0 1.1 Green WR, Chan CC, Hutchins GM, Terry JM. Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Retina. 1:27-55, 1981.
- ↑ 2.0 2.1 Frangieh GT, Green WR, Barraquer-Sommers E, et al. Histopathologic study of nine branch retinal vein occlusions. Archives of Ophthalmology. 100:1132-40, 1982.
- ↑ The Eye Disease Case-Control Study Group. Risk factors for central retinal vein occlusion. Archives of Ophthalmology. 114(5):545-54, 1996.
- ↑ The Eye Disease Case-Control Study Group. Risk Factors for branch retinal vein occlusion. American Journal of Ophthalmology. 116(3):286-96,1993.
- ↑ Ciftci S, Sakalar YB, Unlu K, et al. Intravitreal bevacizumab combined with panretinal photocoagulation in the treatment of open angle neovascular glaucoma. European Journal of Ophthalmology. 19(6):1028-33, 2009.
- ↑ Spaide RF, Chang LK, Klancnik JM, et al. Prospective study of intravitreal ranibizumab as a treatment for decreased visual acuity secondary to central retinal vein occlusion. American Journal of Ophthalmology. 147(2):298-306, 2009.
- ↑ Kondo M, Kondo N, Ito Y, et al. Intravitreal injection of bevacizumab for macular edema secondary to branch retinal vein occlusion. Retina. 29:1242-48, 2009.
- ↑ Ip MS, Scott IU, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Archives of Ophthalmology. 127(9):1101-14, 2009.
- ↑ Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Archives of Ophthalmology. 127(9):1115-28, 2009.
- ↑ Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG; BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1102-1112.e1.
- ↑ Varma R, Bressler NM, Suñer I, Lee P, Dolan CM, Ward J, Colman S, Rubio RG; BRAVO and CRUISE Study Groups. Improved vision-related function after ranibizumab for macular edema after retinal vein occlusion: results from the BRAVO and CRUISE trials. Ophthalmology. 2012 Oct;119(10):2108-18.
- ↑ Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012 Apr;119(4):802-9.
- ↑ Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1.
- ↑ Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol. 2013 Mar;155(3):429-437.e7.
- ↑ Heier JS, Clark WL, Boyer DS, Brown DM, Vitti R, Berliner AJ, Kazmi H, Ma Y, Stemper B, Zeitz O, Sandbrink R, Haller JA. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014 Jul;121(7):1414-1420.e1.
- ↑ Campochiaro PA, Clark WL, Boyer DS, Heier JS, Brown DM, Vitti R, Kazmi H, Berliner AJ, Erickson K, Chu KW, Soo Y, Cheng Y, Haller JA. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology. 2015 Mar;122(3):538-44
- ↑ Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, Whitcup SM; Ozurdex GENEVA Study Group, Li J. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology. 2011 Dec;118(12):2453-60.
- ↑ Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Awh CC, Kunimoto DY, Marcus DM, Wroblewski JJ, King J; SCORE2 Investigator Group. Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical Trial JAMA 2017;317(20):2072-2087.
- ↑ Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Altaweel M, Berinstein DM; SCORE2 Investigator Group. Comparison of Monthly vs Treat-and-Extend Regimens for Individuals With Macular Edema Who Respond Well to Anti–Vascular Endothelial Growth Factor Medications Secondary Outcomes From the SCORE2 Randomized Clinical Trial. JAMA Ophthalmol. 2018;136(4):337-345.
- ↑ The Central Vein Occlusion Study Group: A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion: the CVOS Group N Report, Ophthlamology 102:1434-44, 1995.
- ↑ The Central Vein Occlusion Study Group: Evaluation of grid-pattern photocoagulation for macular edema in central vein occlusion: the CVOS Group M Report. Ophthalmology 102:1425-33, 1995.
- ↑ Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. American Journal of Ophthalmology. 98:271-82, 1984.
- ↑ Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. Archives of Ophthalmology. 104:34-41, 1986.
