Patients with major depressive disorder showed normal ranges of blood markers for inflammation (CRP, IL-6) but lower retinal vessel density, thinner subfoveal choroidal thickness and poorer visual fields. Photo: Mohammad Rafieetary, OD.

The brain is well-established to have countless ties with the eye, given a shared common embryonic origin between the two. This has established the retina as fertile ground for biomarkers of an array of CNS conditions. As one new study found, the link between the retina with major depressive disorder (MDD) is no exception.

The authors of the study wanted to find any potential association of retinal microvasculature abnormalities with depression in a non-geriatric population. Participants with MDD were hospitalized at the University Hospital in Hradec Kralove, Czech Republic. The 50 patients (age: 16 to 55) were compared with 50 controls with no depressive symptoms. Patients were diagnosed with either a single depressive episode (n=26) or recurrent depressive disorder (n=24). Results indicated that microvascular retinal changes did occur in those with depressive disorder when comparison with the control group. This included displaying larger arteriolar and venular calibers, or greater width.

Literature outlines how microvascular changes in form and function are linked to both acute and chronic neuroinflammation. Within the eye, the retinal vascular endothelium is a main participant in inflammatory response, damaging surrounding tissue and hence impairing its function. Since the retina and brain do share an embryonic origin, the study authors “suspect similar microvascular pathology in the retina and in the brain in major depression.”

They report seeing a difference in BMI and education level in women with MDD when compared with controls, possibly explained by depression’s greater prevalence in women. However, no other demographic differences were observed in either sex between groups. The researchers do mention, though, that results concerning possible associations of age, blood cholesterol level and drug resistance with retinal microvascular changes in MDD were inconclusive.

The researchers put their findings into context by outlining the results of similar studies. Retinal vascular abnormalities in patients with major depressive disorder have been previously investigated, with mixed results. One study found no association of retinal microvascular abnormalities with depression symptoms, while others range from finding prenatal depressive symptoms associated with arteriolar widening in pregnant women, to depression and anxiety symptoms associated with wider retinal arteriolar caliber and more.

OCT has also been examined as a possible retinal diagnostic in MDD. One study in this category showed ganglion cell layer and inner plexiform layer volumes were smaller in MDD patients and their choroid thickness was greater. Another reported MDD patients to have lower retinal vessel density, thinner subfoveal choroidal thickness and poorer visual fields.

The authors propose that the sometimes contradictory literature findings point to an observed relationship between depression symptoms and retinal vascular abnormalities, which they explain may be due to imbalanced cytokines initiating proinflammatory processes.

Despite this observation, the researchers caution that “we cannot say for sure what is primary—the development of depression with the resulting cascade of inflammatory processes, or neurogenic inflammation with subsequent development of depressive symptoms; or as some epidemiological studies have shown, that changes in retinal arteriolar and venular diameters are reflective of a wide range of genetic, epigenetic and environmental factors.”

However, what is apparent, they argue, is that “retinal microvascular examination could be a potential screening tool to identify individuals at risk for depression” and that “this examination could possibly be used in the early diagnostics and prevention of depressive disorder.”