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.

Study Overview

• Status: Unknown
• Conditions: Central Retinal Vein Occlusion

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Edmund Tsui, BSc; Phone Number: 5694 (416)603-5694; Email: tsui.edmund@gmail.com
• Study Contact Backup: Name: Tien Wong, BSc; Phone Number: 5694 (416)603-5694; Email: twong@uhnresearch.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
      • Contact: Edmund Tsui, BSc; Phone Number: 5694 (416)603-5694; Email: tsui.edmund@gmail.com
      • Contact: Tien Wong, BSc; Phone Number: 5694 (416)603-5694; Email: twong@uhnresearch.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with central retinal vein occlusion will be recruited from the Retina Clinics of Toronto Western Hospital

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Anti-VEGF group; Patients who are clinically indicated for the intravitreal injection of ranibizumab
Age-matched controls; Group of healthy participants who will be age and gender matched

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative change in retinal blood flow	Retinal blood flow will be measured using Canon Laser Blood Flowmeter	Baseline, 7, 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (LogMAR, EDTRS)	Best Corrected Visual Acuity will be examined using 96% and 10 % contrast EDTRS letter charts	Baseline, 7, 30 days

Collaborators and Investigators

• Sponsor: University of Toronto

Study record dates

Study Major Dates

• Study Start: June 1, 2011

Study Registration Dates

• First Submitted: February 15, 2011
• First Submitted That Met QC Criteria: February 22, 2011
• First Posted (ESTIMATE): February 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 24, 2011
• Last Update Submitted That Met QC Criteria: February 22, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: anti-VEGF; retinal vein occlusion; blood flow
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Retinal Vein Occlusion
• Other Study ID Numbers: CRVO-blood flow study