Several diseases such as systemic lupus erythematosus, rheumatoid arthritis, and obstructive apnea syndrome result in lower choroidal thickness that leads to microvascular changes in the background of chronic systemic inflammation [9–12]. Obesity is known to be a cause of low-grade systemic or chronic inflammation resulting in cytokine, adipokine, and chemokine release . The inflammatory mediators secreted to the blood in obese patients are believed to increase oxidative stress and hypoxia, and the accompanying chronic low-grade inflammation creates a predisposition for vascular endothelial damage and microvascular changes, as in other systemic disorders [14–16]. We similarly aimed to evaluate the ocular perfusion by investigating both the retrobulbar blood flow and choroidal circulation in order to determine microvascular changes in the current study. We found decreased ocular perfusion in obese patients, as indicated by both the decreased retrobulbar ocular blood flow and lower choroidal thickness.
The hemodynamic abnormalities in the retrobulbar circulation were evaluated with CDU. Impaired ocular perfusion is reflected by low PSV and EDV values while the RI and PI parameters indicate vascular resistance. However, there is an acceptance of the fact that RI is more reliable to determine resistance in small diameter vessels such as the retrobulbar vessels while PI shows the resistance for large diameter vessels . The more obese (group 3) individuals had lower CRA and OA PSV values than both the obese (group 2) and normal weight subjects. The CRA EDV values were significantly lower in each obese patient groups than in the healthy group while this was not statistically significantly different between each obese groups. In addition, the OA EDV values were lower in the more obese group but showed no statistically significant difference between the obese groups while showing a statistically significant difference between the more obese group and the healthy group. No statistically significant difference was found between the groups for the vascular index parameters of the OA or CRA. High vascular resistance can result in decreased PSV and EDV values. However, we found reduced PSV and EDV values in obese patients without a change in vascular resistance, including the RI and PI values.
Ocular blood flow changes are correlated with the amount of retrobulbar adipose tissue. Another study has reported significantly decreased IOP levels and increased OA PSV and EDV values in the postoperative period after bariatric surgery related to the decreased BMI values in morbidly obese patients . Lopez et al. have evaluated the effects of decompression surgery on retrobulbar blood flow in patients with Graves’ ophthalmopathy and found a significant decrease in the RI values of the CRA and OA and increased PSV and EDV values of the OA after decompression surgery . We could therefore speculate that increased severity of obesity leads to a change in the vascular resistance and OA flow parameters in parallel to the increase in the retrobulbar adipose tissue and that it can also lead to decreased ocular perfusion including the OA parameters. When we compare the morbid obese studies' results with this current study, we observed that the CRA-PSV tends to be the more affected subparameter in relation to the severity of the obesity among the retrobulbar blood flow parameters and without a vascular resistance change in less obese cases. Similarly, another study has found a decrease only in the OA PSV and EDV values together with decreased CRA PI in morbidly obese patients . On the other hand, the elevated blood cell count, hemoglobin and hematocrit values in obese patients result in an increase in the blood viscosity . There could therefore be another explanation for the potentially decreased retrobulbar ocular perfusion with the increased viscosity caused by the increased hematocrit values resulting in a decreased flow rate in the vessels. The retina and optic nerve head vessels also have an autoregulation system that enables the maintenance of blood flow velocity even when the perfusion pressure is changed. We monitored changes in both the OA and CRA parameters in this study while other studies on morbidly obese patients have focused only on the OA parameter changes [6, 7]. It is possible that autoregulatory mechanisms become effective in protecting the retinal arteriole perfusion when the OA velocity decreases in association with the increasing retrobulbar fat tissue in the morbidly obese.
The choroidal thickness measurements were evaluated in the current study after making sure the groups were similar as regards any factors that could influence the measurement results such as age, gender, and axial length. The measurements were performed at the same time of the day to avoid any effect of the diurnal variation. The choroidal thickness values were found to be significantly lower in the two obese groups compared to the group with normal BMI for all the measurement points. In addition, the choroidal thickness was statistically significantly lower at the FCT, N500, T500, and T1000 measurement points in the BMI > 35 group compared to the BMI 30 to 35 group. A statistically significant negative correlation was found between the choroidal thickness and the BMI, FCT, N500, N1000, T500, T1000, and T1500 values. Our results are consistent with other studies in the literature [20, 21].
We found a decreased blood flow rate as indicated by our results related to both the retrobulbar and choroidal circulation in this study. The ciliary artery, a branch of the ophthalmic artery, plays a role in the choroidal circulation, and any ophthalmic artery velocity decrease could therefore indicate choroidal circulation changes. We similarly found significantly decreased OA PSV and EDV values in the obese group compared to the healthy group and supported this finding with a decreased choroidal volume in the two obese groups.
Several studies have reviewed the underlying mechanisms of the microvascular changes as related to obesity. The choroidal blood flow decreases with the activation of the choroidal circulation-related sympathetic efferent nerves and the secretion of noradrenaline, while increasing with NO secretion by the parasympathetic efferent nerves, both under the regulation of the autonomic nervous system . The level of nitrous oxide (NO), a vasodilator molecule of endothelial origin that regulates the ocular blood flow and has a positive effect on IOP regulation, is low in obese patients [23, 24], while the level of vasoconstrictor molecules such as endothelin-1 (ET-1) and Angiotensin-II (Ang-II) have been found to increase in the serum in correlation with the BMI [25, 26]. We therefore believe the decreased thickness of the choroid that is rich in vascular supply in our cases is due to the balance between the vasodilator and vasoconstrictor agents shifting towards vasoconstriction.
The IOP was found to be statistically significantly high in the obese patients compared to the control group in this study (although still within the normal range) and there was also a statistically significant positive correlation between the BMI and the IOP. These results are consistent with the literature [27–29]. The IOP elevation in obese patients is explained with vascular and mechanical mechanisms. Accordingly, the increased IOP in these patients has been associated with increased oxidative stress due to the hyperleptinemia  that damages the trabecular meshwork , and the increased episcleral venous pressure related to the increased orbital fat mass  and resultant decreased aqueous outflow . The Beaver Dam Eye study group has reported an increased IOP value in correlation with an increased BMI value . Obesity has been found to be an independent risk factor in IOP elevation [33, 34]. Similarly, we encountered IOP elevation that was parallel to the increased BMI in obese patients in this study.
Evaluation of our results in the light of this information showed that both the retrobulbar ocular perfusion and the choroidal vascular perfusion could decrease in correlation with the severity of the obesity as a result of the increased inflammatory mediators related to the increased adipose tissue, the vascular endothelial dysfunction developing in the presence of increased oxidative stress and hypoxia; the elevated blood cell count, hemoglobin and hematocrit values; and the shift in the balance between the vasodilator and vasoconstrictor agents towards vasoconstriction.
Our study had various limitations. The first one was the small size of our groups. Another limitation was the lack of information on the obesity duration of the subjects and the blood levels of the inflammatory cytokines named adipokines.
In conclusion, we found that obese patients had higher IOP values while the choroidal thickness and the CRA and OA PSV and EDV values were lower compared to the control group. This indicates decreased retrobulbar and ocular blood flow with an effect on the vascular perfusion. We also found decreased choroidal thickness together with decreased CRA and OA PSV values as the severity of the obesity increased. The results indicate that obesity can create a suitable background for ocular pathologies by causing microvascular changes as a result of both the increase in IOP and the decrease in the retrobulbar and choroidal blood flow.