Retinal Blood Flow in Response to an Intravitreal Injection of Ranibizumab for Central Retinal Vein Occlusion (CRVO)

Retinal Blood Flow in Response to an Intravitreal Injection of Ranibizumab for Central Retinal Vein Occlusion

Ranibizumab (Lucentis, Genentech) is an off-label drug used for the clinical treatment of central retinal vein occlusion, which is one of the most common retinal vascular disorders. Despite its clinical effectiveness, concerns remain regarding the systemic effects of the drug and previous studies have noted retinal arteriolar vasoconstriction following a ranibizumab injection. We aim to provide a physiological basis to these observations by assessing retinal blood flow before and after the ranibizumab injections. Specifically, we will assess the blood flow parameters (i.e. retinal vessel diameter, velocity & flow) immediately before the first injection and post-injection over a follow-up continued treatment period.

Ranibizumab is an antibody fragment designed to inhibit the activity of Vascular Endothelial Growth Factor (VEGF), which is responsible for the neovascularization and retinal edema responsible for interference of normal vision in central retinal vein occlusion. However, VEGF has a role in the vasculature as a vasodilator where it alters the expression of tight junction proteins and upregulates the release of the vasodilator nitric oxide. Consequently, intravitreal ranibizumab injections could result in systemic inhibition of VEGF, leading to long-term retinal arteriolar vasoconstriction and potentially adverse cerebrovascular and myocardial accidents. Therefore, evaluating retinal blood flow would provide a physiological foundation to this concern and provide physicians with valuable information regarding the risks of continued ranibizumab therapy.

Given the role of VEGF as a vasodilator in the vasculature where it works to alter the expression of tight junction proteins and the production of vasoactive substances especially nitric oxide, inhibiting this molecule with ranibizumab could result in vasoconstriction in these vessels. We hypothesize that vasoconstriction and decreased retinal blood flow will be observed after an intravitreal injection of ranibizumab for treatment of central retinal vein occlusion.

Inclusion Criteria:

• Age > 50 years
• central retinal vein occlusion scheduled for first intravitreal injection of ranibizumab as part of their clinical care

Exclusion Criteria:

• previous history of intravitreal therapy,
• history of thromboembolic events,
• glaucoma or an intraocular pressure >21 mmHg
• diabetes mellitus or altered blood viscosity syndromes
• blood donation in the previous 2 weeks
• refractive error of +/- 6.00 DS and/or 2.00 DC