Diabetic retinopathy is known to be related to biochemical pathway changes caused by prolonged hyperglycemia with subsequent hypoxia-induced changes.
86,87 In evaluating the role of retinal oximetry in diabetic retinopathy, it is important to remember the technology's limitations. For example, the devices and studies are unable to calculate the oxygen tension within certain portions of the retina. Additionally, as described above, many factors, such as retinal pigmentation, can influence the retinal oximetry measurements. Using oxygen saturation measurements cannot provide information directly on the mechanism of diabetic vascular changes. However, the findings thus far are supportive of theories that point to blood shunting and bypassing of nonperfused areas resulting in increased oxygenation of venules in the retina. Multiple studies, using both the Vesselmap and Oxymap systems, have demonstrated that retinal oximetry may have predictive value as a supplemental tool in determining the severity of diabetic retinopathy.
88,89
Using a commercially available scanning laser ophthalmoscope (Optos 200TX; Optos, Dunfermline, Scotland) combined with commercial software from Oxymap, a recent study by Blair and colleagues
42 measured retinal oximetry in 46 healthy patients, as well as 135 diabetic patients with and without diabetic retinopathy. Their primary finding was that the retinal venous saturation was increased in non-proliferative diabetic retinopathy, whereas in proliferative diabetic retinopathy the retinal arterial diameter was decreased, and venous oxygen saturation was increased. Another group, led by Kashani et al.,
90 applied a retinal oximetry device using hyperspectral computed tomographic imaging spectroscopy. This device was added to a conventional fundus camera and was used to measure retinal vascular oxygen content in human subjects. Similar to other studies, arteriovenous difference was significantly lower in patients with proliferative diabetic retinopathy than healthy control subjects (14% vs. 26%). Although these studies demonstrate that venous oxygen saturation is likely increased in diabetic retinopathy, additional data demonstrating a role for retinal oximetry to guide clinical decision-making is likely necessary for retinal oximetry to become practically useful for clinicians.
Other studies have sought to explore the clinical predictive value of retinal oximetry. In a study of 722 patients, Bek et al.
89 found that venous oxygen saturation contributed more than hemoglobin A1c to retinopathy grade, using either diabetic macular edema or proliferative diabetic retinopathy as an endpoint. However, it is important to note that the authors measured the contributions of several variables, all of which contributed less than 15% of the variation in retinopathy grade. Furthermore, the authors do not address whether they controlled for factors that can influence oxygen saturation measurements, such as fundus pigmentation, when selecting their patient population. Another study by Bek et al.
91 demonstrated that oxygen saturation in retinal arterioles prior to treatment with an anti-VEGF medication contributed to predicting visual acuity and central retinal thickness after treatment. Their findings validated the finding of increased oxygen saturation in large retinal venules that has been described in prior studies.
92 Interestingly, although the study by Bek et al.
91 noted that venous oxygen saturation was increased in patients with diabetic retinopathy (as seen in other studies), the authors did not see a significant decrease in venous oxygen saturation following anti-VEGF treatment, although this study had a relatively small sample size (34 patients with retinal oximetry after treatment). A similar study examined these effects after pan-retinal photocoagulation and concluded that the effects of retinal photocoagulation in diabetic retinopathy was not correlated with changes in oxygen saturation in larger retinal vessels.
93 It is important to note that these studies did not utilize fluorescein angiography (FA), which is the current gold standard for evaluation of the vascular in diabetic retinopathy. Comparing FA findings with retinal oximetry (as studies have done for retinal vein occlusion, described below) can help to validate retinal oximetry as a clinical measurement. Further, it will be necessary to demonstrate that retinal oxygen saturation measurements can influence clinical decision-making in a meaningful way relative to FA in order for it to become a standard clinical measurement. Combined, these studies suggest that, although increased venous oxygen saturation is seen in patients with diabetic retinopathy, significant changes in oxygen saturation are not necessary to see positive effects of treatment. However, if replicated, the ability to predict treatment response reported by Bek et al. provides a potential clinical application, as retinal oximetry could conceivably be used by clinicians to help provide patients with assistance in selecting treatment options, especially if this predictive value can be demonstrated in additional treatment options and pathologies.