**14. Cardiovascular disease**

The association between cardiovascular disease and diabetic retinopathy was studied mainly in patients with mild retinal lesions. A recent meta-analysis was

performed on 7604 individuals with type 2 diabetes from 8 prospective populationbased surveys that were monitored for 5.9 years (3.2 to 10.1 years) where DME was identified in retinal photographs. DME was observed in 0.5% to 7.6% of the participants and was related to an increased risk of first-ever cardiovascular disease incidence rate ratio 1.65 and fatal cardiovascular disease - incidence rate ratio 2.85. The incidence rate ratio for first-ever coronary heart disease was 1.57 and for fatal coronary heart disease - 3.55. These associations were consistent after multivariable adjustment for vascular risk factors, including smoking, systolic blood pressure, use of hypertension medication, total cholesterol level, and body mass index. When duration of diabetes, use of treatment for diabetes, and glycosylated hemoglobin level were included in the multivariable model, the relationship remained significant [65]. This analysis resonates with an early report on markers for subclinical cardiovascular disease in diabetic patients: CSME was associated with a high coronary artery calcium score (odds ratio, OR 2.86), low ankle-brachial index (OR 4.08) and high ankle-brachial index (OR 21.4) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes, but there was significant association with carotid intima-media thickness or carotid stenosis, defined as >25% stenosis or presence of carotid plaque [66]. The diagnosis of CSME in these studies was based on fundus photographs; had OCT been used as a more sensitive imaging modality [13, 45, 67], the proportion of DME patients with increased cardiovascular risk could have been even higher. In clinical practice, confirmed or probable decompensated coronary artery disease is usually associated with more severe retinal ischemia, unstable response to treatment and higher risk of cardiovascular complications after intravitreal anti-VEGF if used in the course of an acute episode. The extent of macular edema and rate of its recurrence decrease notably after successful angioplasty or coronary bypass graft, however these patients remain at high risk as they are prone to new coronary heart attacks, severe infections and vision-threatening complications – neovascular glaucoma, ischemic diabetic optic neuropathy, vitreous hemorrhages and chronic macular edema (**Figures 1**, **3** and **4**).
