Short summary

Branch retinal vein occlusion (BRVO) is often complicated by macular edema, possibly leading to severe visual loss or blindness. Treatment is repeated, intravitreal injections, which burdens both patient and society. 

Thus, we wish to evaluate whether addition of a central navigated laser, a novel laser delivery system, can improve the treatment by reducing number of intravitreal treatments, while maintaining good visual outcome for the patients.

Rationale

Problem statement

Retinal vein occlusion (RVO) is a common cause of visual loss in the elderly with a 15-year incidence of 2.3% of the population. Seventy eight percent of patients have an occlusion of a branch vein, which is diagnosed based on intraretinal hemorrhages in the retinal sector drained by the affected vein. In time, hemorrhages often resorb, but vision-threatening ischemia may arise. This leads to an upregulation of VEGF, which then causes neovascularization, vasodilation and increased vascular permeability, leading to macular edema, the most common reason for vision loss in BRVO. 

Until a few years ago, treatment included observation or macular grid pattern laser photocoagulation, which could often stabilize the disease but rarely led to improvement in visual function. In recent years, better visual outcome has been demonstrated with intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors like ranibizumab or aflibercept. Even though this is encouraging, patients on average need nine injections in the first 12 months. The high number of repetitive treatments is a concern for patients as well as society due to the invasiveness of the treatment and the high price of the drug. Hence, it is warranted to develop newer treatment regimens combining the efficacy of intravitreal anti-VEGF with the potential stabilizing effect of laser photocoagulation. This might minimize the number of injections and its side effects, while still providing excellent visual outcomes for the patients. 

In addition, it is important to identify non-invasive markers of disease activity and treatment outcome in order to enable individualised treatment in this potentially blinding disease. 

Purpose

In a 12-month prospective, randomized 1:1 study of patients with branch retinal vein occlusion (BRVO) and macular edema, we aim to 

(1) examine the treatment response of patients treated with intravitreal aflibercept (Eylea) and navigated retinal laser (Navilas®)(Group 1) as compared to patients treated with intravitreal aflibercept only (Group 2), and 

(2) identify non-invasive retinal biomarkers (retinal oxygen saturation, macular ischemia and retinal vascular arteriolar and venular calibre) for successful treatment outcome.

Description of the cohort

Patients with BRVO with foveal center-involved macular edema in the study eye.

• Best-corrected visual acuity (BCVA) 35-80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (0.1-0.8 Snellen equivalent) in the study eye at baseline (BL).

• Age ?18 years.

• Central retinal thickness > 300 ?m in the study eye at BL.

• Diagnosis ? 6 months prior to the study.

• No active retinal or iris neovascularizations in the study eye at any time.

• No cataract, vitreous hemorrhage or other clouding conditions that prevent retinal laser photocoagulation in the study eye at M3. 

• No prior anti-VEGF treatment or macular laser photocoagulation in the study eye.

• No macular edema and/or increased retinal thickness due to other potential causes than BRVO

• No uncontrolled hypertension (blood pressure ? 160/110 mmHg).

Data and biological material

We collect clinical data on e.g. visual acuity, central retinal thickness, structural parameters, and markers of retinal ischemia.

Collaborating researchers and departments

Professor, Consultant Jakob Grauslund, DMSci, PhD (Head of study)1

Professor, Consultant Torben Lykke Sørensen, DMSci2

Consultant Jesper Vestergaard, MD1

Associate Professor, Consultant Inger Christine Munch, PhD2

Adjunct Professor, Head of Reading Centre Tunde Peto, PhD, International collaborator

Associate Professor Ryo Kawasaki, PhD, International collaborator