What is the pathophysiology of Central Retinal Vein Occlusion (CRVO)?

Pathophysiology of Central Retinal Vein Occlusion (CRVO)

Central retinal vein occlusion (CRVO) primarily develops through thrombus formation in the central retinal vein, leading to increased retinal capillary pressure, vascular permeability, and potential retinal neovascularization. 1

Primary Pathophysiological Mechanisms

Vascular Occlusion and Hemodynamic Changes

• Thrombus formation in the central retinal vein is the initiating event 1
• The occlusion typically occurs at or near the lamina cribrosa, where the central retinal vein shares a common adventitial sheath with the central retinal artery 2
• Anatomical factors at the optic disk, including the cribriform plate and scleral ring, contribute to the development by creating a confined space where neurovascular compression can occur 2
• Following occlusion, there is a gradual reduction in retinal blood flow velocity 3

Inflammatory and Growth Factor Cascade

• VEGF (Vascular Endothelial Growth Factor) plays a crucial pathogenic role in the development of macular edema following CRVO 3
• Inflammatory cytokines increase over time, causing more severe inflammation 3
• The expression of these inflammatory factors contributes to a condition increasingly resistant to anti-VEGF therapy in some patients 3

Disease Progression

• CRVO can progress from non-ischemic to the more severe ischemic type 3
• This progression results in excessive VEGF expression, which can lead to complications such as neovascular glaucoma 3
• Leukocyte abnormalities are associated with CRVO and may contribute to disease progression 3

Risk Factors and Associated Conditions

• CRVO is common in people with underlying vascular diseases:
  • Arteriosclerosis 3
  • Hypertension 3
• Hyperviscosity syndromes can cause CRVO, particularly bilateral cases
  • Waldenstrom's macroglobulinaemia is a notable example that can present with bilateral CRVO due to serum hyperviscosity 4

Clinical Consequences

• Macular edema is the primary cause of vision loss in CRVO 1
• Other vision-threatening complications include:
  • Macular ischemia 5
  • Neovascular glaucoma 5
  • Intraretinal hemorrhage 2

Pathophysiological Insights for Treatment

• Understanding the role of VEGF has revolutionized CRVO treatment through anti-VEGF therapy 3
• The complex pathogenesis involving multiple inflammatory cytokines explains why some patients have refractory or recurring edema despite anti-VEGF treatment 3
• Surgical approaches like radial optic neurotomy aim to address the anatomical component by decompressing the central retinal vein at the level of the scleral ring and cribriform plate 2
• In cases of hyperviscosity-related CRVO, addressing the underlying cause through plasma exchange can be effective 4

Important Clinical Considerations

• The pathophysiology suggests that early intervention is crucial to prevent progression from non-ischemic to ischemic CRVO
• Multiple pathogenic mechanisms beyond VEGF indicate that combination therapies may be necessary for some patients
• Regular monitoring with imaging techniques like optical coherence tomography is essential to track disease progression and treatment response 5