Central Retinal Vein Occlusion vs. Branch Retinal Vein Occlusion: A Comparative Overview

Isaamuddin Alvi

Introduction

Retinal vein occlusion (RVO) is the second most common vascular disease of the retina after diabetic retinopathy, with a growing global burden. In 2008, an estimated 16.4 million people were affected worldwide, increasing to 28.06 million by 2013. Of these cases, 23.38 million involved branch retinal vein occlusion (BRVO), while 4.67 million were due to central retinal vein occlusion (CRVO) (1).

RVO occurs when the retinal veins become blocked, leading to fluid accumulation, haemorrhages, and potential vision impairment. It is broadly classified into central and branch occlusions, each with distinct clinical features and implications (2). Understanding these differences is essential for timely diagnosis and effective treatment. This article explores their causes, risk factors, symptoms, diagnostic methods, treatment options, and prognoses.

Risk Factors

Both CRVO and BRVO share several risk factors, including hypertension, diabetes mellitus, hyperlipidaemia, glaucoma, blood clotting disorders, smoking, and advanced age. However, there are some distinctions between the two conditions. CRVO is more commonly associated with systemic circulatory disorders and hypercoagulability disorders, which make individuals more prone to blood clots. It may also be related to optic nerve head crowding. On the other hand, BRVO is often associated with localised vascular abnormalities within the retina and can be caused by arteriovenous compression, where a thickened artery compresses an adjacent vein (3).

Pathophysiology

Visual loss in retinal vein occlusion (RVO) is primarily driven by macular oedema, making its pathogenesis crucial for understanding treatment mechanisms. When a retinal vein becomes blocked, blood flow is partially obstructed, increasing pressure within the vessel (4). This elevated pressure leads to fluid leakage into the retinal tissue, following Starling’s law, resulting in macular oedema (5). The accumulation of fluid and proteins within the retina increases oncotic pressure, further exacerbating the oedema, impairing capillary circulation, and causing ischaemia. Notably, even in non-ischaemic RVO cases, some degree of retinal ischaemia is usually present (6).

There is evidence to suggest that inflammation plays a role in the progression of RVO. Studies have shown elevated levels of inflammatory cytokines—such as interleukin (IL)-6 and IL-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF)—in the vitreous and aqueous humour of RVO patients, particularly those with central retinal vein occlusion (CRVO) (7). VEGF, which is produced in response to tissue hypoxia, is a key factor contributing to increased vascular permeability, neovascularisation, and macular oedema. Research in animal models has demonstrated that sustained exposure to VEGF leads to retinal vessel dilation, breakdown of the blood-retinal barrier, and new vessel formation (8).

The sudden ischaemia seen in BRVO and especially CRVO is believed to trigger excessive VEGF production, primarily from retinal pigment epithelial cells, endothelial cells, and Müller cells. Elevated VEGF levels correlate closely with the severity of macular oedema and the extent of retinal ischaemia. Furthermore, VEGF has been linked to iris neovascularisation and increased vascular permeability in ischaemic CRVO cases. Even if venous obstruction resolves, macular oedema can persist due to a self-sustaining cycle of VEGF-induced vascular permeability, capillary damage, and further ischaemia, reinforcing chronic fluid accumulation and retinal dysfunction (4).

Understanding this cycle provides insight into why anti-VEGF therapies have become a cornerstone of RVO treatment, aiming to reduce macular oedema and prevent long-term vision loss.

Clinical Presentation

CRVO typically presents as a sudden, painless reduction of vision in one eye. Patients may experience blurred or dimmed vision, central scotoma, and, in severe cases, neovascular complications that lead to increased intraocular pressure and possible glaucoma. In contrast, BRVO often results in partial vision loss that typically affects one quadrant of the visual field. Blurred or distorted vision may fluctuate, and the symptoms are usually less severe than those seen in CRVO and can present as an asymptomatic incidental finding. However, BRVO can still cause macular oedema, which may impair vision (9).

FeatureCRVOBRVO
Affected AreaAll Quadrants of RetinaSegment of the retina
Visual Loss SeveritySevereMild to moderate
Main CauseSystemic FactorsLocal Vascular Abnormalities
Treatment ApproachMore aggressive, includes anti-VEGF and steroidsOften resolves spontaneously, may require focal laser

Clinical Examination

Diagnosing CRVO and BRVO involves a comprehensive eye examination, including fundoscopic evaluation, optical coherence tomography (OCT), and fluorescein angiography. A fundoscopic examination of CRVO reveals diffuse retinal haemorrhages in all quadrants of the retina, whereas BRVO shows haemorrhages confined to a segment of the retina following a blocked branch vein (10). OCT is used to detect macular oedema and measure retinal thickness (11), while fluorescein angiography highlights blood flow patterns and identifies the extent of vessel blockage (12).

Treatment

The management of both CRVO and BRVO focuses on addressing the underlying systemic conditions and mitigating vision loss. General treatment strategies include controlling hypertension, diabetes, and hyperlipidaemia, as well as adopting lifestyle modifications such as a healthy diet, regular exercise, and smoking cessation (13,14). For CRVO, treatment options include anti-VEGF injections such as ranibizumab, aflibercept, or bevacizumab to reduce macular oedema. Intravitreal steroids, such as the Ozurdex dexamethasone implant, may also be used to control inflammation thereby treating macula oedema (15). In cases of neovascular complications, pan-retinal photocoagulation laser can be performed to reduce ischaemic drive and further neovascularisation, while neovascular glaucoma management may require surgical interventions or laser destruction of the ciliary body (16).

BRVO is typically managed with anti-VEGF injections to improve vision and reduce macular swelling. Focal laser therapy may be considered in cases of persistent macular oedema, while mild cases may be monitored closely as some resolve spontaneously. Since BRVO has a better visual prognosis than CRVO, the need for aggressive intervention is usually lower (17).

Prognosis

The long-term prognosis of CRVO and BRVO varies significantly. CRVO carries a higher risk of permanent vision loss due to widespread retinal involvement and an increased chance of complications such as neovascular glaucoma. Regular monitoring and intervention are often required to preserve vision. In contrast, BRVO has a better visual recovery potential, particularly with early treatment. Some cases may experience spontaneous resolution, and the risk of severe complications is lower than in CRVO. Nevertheless, long-term follow-up is essential to ensure that macular oedema or other complications do not develop over time (18).

Conclusion

In summary, CRVO and BRVO are two forms of retinal vein occlusion with distinct characteristics. CRVO affects the entire retina, leading to more profound vision loss and a higher risk of complications, whereas BRVO involves only a segment of the retina, resulting in milder symptoms and a better visual prognosis. Early diagnosis and treatment are crucial in managing both conditions effectively. Individuals at risk should undergo regular eye examinations, manage systemic health conditions, and adopt a healthy lifestyle to minimise the likelihood of retinal vein occlusion. Understanding these differences allows for timely intervention and better outcomes, ensuring optimal visual health.

References

  1. Song P, Xu Y, Zha M, Zhang Y, Rudan I. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors. Journal of global health. 2019 Jun;9(1).
  2. Romano F, Lamanna F, Gabrielle PH, Teo KY, Parodi MB, Iacono P, Fraser-Bell S, Cornish EE, Nassisi M, Viola F, Agarwal A. Update on retinal vein occlusion. The Asia-Pacific Journal of Ophthalmology. 2023 Mar 1;12(2):196-210.
  3. Ørskov M, Vorum H, Bjerregaard Larsen T, Vestergaard N, Lip GY, Bek T, Skjøth F. A review of risk factors for retinal vein occlusions. Expert Review of Cardiovascular Therapy. 2022 Sep 2;20(9):761-72.
  4. Lendzioszek M, Bryl A, Poppe E, Zorena K, Mrugacz M. Retinal Vein Occlusion–Background Knowledge and Foreground Knowledge Prospects—A Review. Journal of Clinical Medicine. 2024 Jul 5;13(13):3950.
  5. Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, Martin JF, Hykin PG. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Archives of ophthalmology. 2002 Dec 1;120(12):1644-50.
  6. Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, Quinlan E, Zimmer-Galler I, Haller JA, Solomon SD, Sung JU. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Molecular Therapy. 2008 Apr 1;16(4):791-9.
  7. Funk M, Kriechbaum K, Prager F, Benesch T, Georgopoulos M, Zlabinger GJ, Schmidt-Erfurth U. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Investigative ophthalmology & visual science. 2009 Mar 1;50(3):1025-32.
  8. Ozaki H, Hayashi H, Vinores SA, Moromizato Y, Campochiaro PA, Oshima K. Intravitreal sustained release of VEGF causes retinal neovascularization in rabbits and breakdown of the blood–retinal barrier in rabbits and primates. Experimental eye research. 1997 Apr 1;64(4):505-17.
  9. Rogers SL, McIntosh RL, Lim L, Mitchell P, Cheung N, Kowalski JW, Nguyen HP, Wang JJ, Wong TY. Natural history of branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010 Jun 1;117(6):1094-101.
  10. Ho M, Liu DT, Lam DS, Jonas JB. Retinal vein occlusions, from basics to the latest treatment. Retina. 2016 Mar 1;36(3):432-48.
  11. Kang JW, Yoo R, Jo YH, Kim HC. Correlation of microvascular structures on optical coherence tomography angiography with visual acuity in retinal vein occlusion. Retina. 2017 Sep 1;37(9):1700-9.
  12. Thomas AS, Thomas MK, Finn AP, Fekrat S. Use of the ischemic index on widefield fluorescein angiography to characterize a central retinal vein occlusion as ischemic or nonischemic. Retina. 2019 Jun 1;39(6):1033-8.
  13. O’Mahoney PR, Wong DT, Ray JG. Retinal vein occlusion and traditional risk factors for atherosclerosis. Archives of Ophthalmology. 2008 May 1;126(5):692-9.
  14. Lendzioszek M, Mrugacz M, Bryl A, Poppe E, Zorena K. Prevention and Treatment of Retinal Vein Occlusion: The Role of Diet—A Review. Nutrients. 2023 Jul 21;15(14):3237.
  15. Singer MA, Jansen ME, Tyler L, Woods P, Ansari F, Jain U, Singer J, Bell D, Krambeer C. Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series. Clinical Ophthalmology. 2016 Dec 19:31-8.
  16. Clarkson JG, Gass JD, Curtin VT, Norton EW, Blankenship GW, Flynn HW, Mulé M, Leyden K, Guice I, Liang J, Diddie KR. Argon laser photocoagulation for macular edema in branch vein occlusion. American Journal of Ophthalmology. 2018 Dec 1;196:xxx-viii.
  17. Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, Ying GS. Retinal vein occlusions preferred practice pattern®. Ophthalmology. 2020 Feb 1;127(2):P288-320.
  18. Yin S, Cui Y, Jiao W, Zhao B. Potential prognostic indicators for patients with retinal vein occlusion. Frontiers in Medicine. 2022 May 25;9:839082.

Leave a Reply