Quantative investigation of retinal layers and fundus microvascular structures in bipolar disorder

Introduction: Retinal structures can provide reliable information about the cerebral and cerebrovascular system since there are many similarities between anatomic, physiological and pathological features between the retinal vascular and neural structures. Recently, narrowing of the arterioles in the retinal vascular system and widening of the venules have been detected in studies performed in major depressive disorder and schizophrenia. However, only a study of retinal structures in bipolar disorder was found in our literature search. Neurotrophins contribute to their function as proliferative and mitogenic effects, such as the maintenance and viability of tissues. Retinal vascular and neuronal structures are susceptible to these effects of neurotrophins and have been observed in different clinical populations in which neurotrophin levels are associated with retinal structures. Variations in neurotrophin levels may be observed at different periods of bipolar disorder. Brain derived growth factor (BDNF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) are important growth factors. In this study, neurotrophin levels, neural and vascular structures and possible changes in retinal structures and their associations were investigated in different periods of bipolar disorder. Materials and Methods: A total of 41 patients with bipolar disorder who were in 13 manic episodes, 14 in depressive period and 14 in remission according to DSM-IV criteria and 31 healthy volunteers were included in this study. A sociodemographic data form was applied to all participants. The participants were evaluated with the Hamilton Depression Rating Scale and Young Mania Rating Scales. Afterwards, participants were evaluated with Heidelberg OCT Spectralis (Heidelberg, Germany) for orbital tomography and with TRC-50DX (Topcon, Japan) for retinal imaging. Before retinal fundus photography, 1 ml of 1% cyclopentolate HCl was added dropwise to each eye of the individuals and waited 30 minutes for midratic effect. Then blood samples were taken from the antecubital vein to a biochemistry tube. Results: There was no significant difference between the bipolar disorder group and the healthy control group in terms of fundus retinal vein measurements and also no significant difference between subgroups of bipolar disorder groups including manic, depressive and remission episode groups. Blood levels of growth factors did not differ between the bipolar disorder and healthy control groups and also between the subgroups of bipolar disorder group. When bipolar disorder and healthy control groups are compared in terms of the optical coherence tomography (OCT) measurements, there was a decrease in the thickness of R-GCL1 and R-GCL3 in the bipolar disorder group compared to healthy controls. When subgroups of bipolar disorder group are compared, more decrease in R-RNFL4 thickness is found in the remission group compared to mania, and in mania compared to depression group. In healthy control group, there was a positive correlation between VEGF and CRVE, MVD and there was a negative correlation between FGF and R-Retina2, R-Retina3, R-Retina5, L-Retina2, L-Retina3, L-Retina5, and also negative correlation between EGF and R-RNFL3, L-RNFL2. In the bipolar disorder group, there was a negative correlation between age of disease onset and CRVE, MVD, and there were positive correlations between age and CRAE, MAD, and between hospitalization number and CRAE, MAD, CRVE, MVD. In the model that the CRAE / CRVE ratio is dependent and the growth factors are independent variables, a result is found to be significant in bipolar disorder group. According to the model, VEGF was found to be the predictor of CRAE / CRVE in the bipolar disorder group. Conclusion: It is concluded that there are no abnormalities of the retinal structures in the absence of metabolic stress factors in bipolar disorder. Keywords: bipolar disorder, optical coherence tomography, retinal fundus photography, retinal structures