An important consideration regarding these studies is how EZ layer disruption was evaluated since they do not define a clear cutoff to distinguish disrupted from undisrupted layers. It appeared that the results may be consistent and objective only on condition that trained observers are enrolled and adequate scores defined.
14 However, these constraints prevent comparing. For all these reasons, a quantitative tool, automatized and easy to use, could significantly progress the analysis of the photoreceptor layer. Advances in OCT imaging enabled the reconstruction of a en face view of the photoreceptor layer
35–38 at different depths. A strong relationship was recently established between EZ reflectivity and cone density measured with a high-resolution adaptive optics camera in the same perifoveal area.
16,17 In the current study, in diabetic eyes with resolved DME, we observed a 20% decrease in EZ reflectivity compared to diabetic eyes with no history of DME. Furthermore, reflectivity in diabetic eyes without a history of DME was also lower than in control eyes. Interestingly, Lombardo et al.
39 found a subtle decrease of parafoveal cone density in type 1 diabetic patients without maculopathy compared with age-matched control subjects via high-resolution adaptive optics retinal imaging. This decrease reached approximately 10% of the cone density, a result comparable with the 7.9% difference in reflectivity that we observed. It should be noted that decrease in reflectivity does not necessary imply a photoreceptor loss since modified adaptive optics scanning laser ophthalmoscopy (AO/SLO) techniques, allowing to image the ISs regardless of the status of OSs, have shown that enlarged photoreceptor bodies are still present in the dark areas even though it is not known if these remnant photoreceptor are functional.
40 The origin of this decrease was not clearly elucidated. There is an ongoing debate to determine whether diabetic retinal neuropathy is the effect of vascular DR or is primarily caused by direct neurologic damage from chronic hyperglycemia. For instance, Van Dijk et al.
41 demonstrated that there is retinal neurodegeneration and neuroglial cell apoptosis even in the early stages of DR. Furthermore, a retinal neurodegeneration has been reported to occur before any microcirculatory abnormalities. Increased rate of photoreceptor apoptosis and activation of glial cells are major factors identified in retinal neurodegeneration.
42 A vascular cause can also be suspected since abnormal deep retinal capillary networking and nonperfusion were observed in the outer nuclear layer in diabetic eyes.
43,44 Such outer retinal impairment has functional consequences: we observed a relationship between reflectivity and VA (
Supplementary Material S6). Others have observed that disruption of the IS/OS junction was correlated with a significant decrease in retinal sensitivity in DME eyes.
45