Short summary

Diabetic macular edema (DME) is the leading cause of visual impairment among the 300,000 Danish patients with diabetes and will in time affect 29% of patients. Because of DME, 550 intravitreal injections were given at Odense University Hospital in 2014 with medicine expenses approximating 3.3 million DKK. We hypothesize that combination therapy with intravitreal aflibercept and a new computer navigated photocoagulations system (Navilas®) leads to a decreased need for intravitreal injections. ADDENNDUM is a 12-moth prospective randomized 1:1 study to compare intravitreal aflibercept and Navilas® laser with intravitreal aflibercept and conventional Pascal laser in DME treatment.

Rationale

Diabetic retinopathy (DR) is the most common complication among the 300,000 Danish patients with diabetes. Amongst those with diabetes, diabetic macular edema (DME) is a leading cause of visual impairment and will in time affect 29% of all patients.

It was established by the Early Treatment Diabetic Retinopathy Study (ETDRS) that focal/grid laser photocoagulation reduces the risk of visual loss in patients with DME but with a small likelihood of visual improvement. In recent years intravitreal anti-VEGF agents like bevacizumab, ranibizumab and aflibercept have consistently demonstrated efficacy and visual improvement in DME-treatment. However, a high number of injections is needed per patient to achieve sustainable visual improvement. Diabetic Retinopathy Clinical Research Network (DRCR.net) showed, that the median number of intravitreal ranibizumab injections was 9 in the first and 3 in the second year.

The burden of intravitreal injections is a concern and it is substantial both for patients as well as the health care system. Because of DME, 550 intravitreal injections were given at Odense University Hospital in 2014. The medicine expenses of this approximate 3.3 million DKK and with an increasing prevalence of diabetes the number is expected to rise significantly for the years to come.

This calls for initiatives like a more cost-effective treatment and a better understanding of underlying predictors of successful treatment in order to improve and individualize treatment.

Description of the cohort

Criteria of inclusion:

• Diabetes mellitus
• Clinically significant macular edema in the study eye.      
• Central retinal thickness > 300 um in the study eye.
• Best corrected visual acuity 35-75 ETDRS letters (0.10-0.63 Snellen equivalent) in the study eye.
• Age 18-99 years.

Patients will be recruited in the Region of Southern Denmark and included in the study based on clinical examination.

Data and biological material

• Systemic biomarkers: Age, type of diabetes, duration of diabetes, health history, smoking status, blood pressure, body mass index, hemoglobin A1c, albumin excretion rate, glomerular filtration rate, serum creatinine, creatinine clearance.
• ETDRS BCVA measurement.
• Intraocular pressure.
• Heidelberg fluorescein angiography, incl. measurement of area of foveal avascular zone (FAZ).
• Topcon 3D OCT-2000 spectral domain OCT.
• Retinal vessel geometry measurements.
• Oxymap retinal oximetry measurement.

Collaborating researchers and departments

Department of Ophthalmology, Odense University Hospital

• Clinical professor and primary supervisor Jakob Grauslund, MD, PhD, DMSci

Reading Centre, Department of Research and Development and Moorfields Eye Hospital, NHS Foundation Trust

• Head of Reading Centre and Medical Retina Specialist Tunde Peto, PhD