**6.2 Hyperreflective retinal foci**

SD-OCT imaging of diabetic retinopathy identified an additional intraretinal pathology which was visualized as hyperreflective dot or foci (HF) in few cases of DME [47]. Bolz et al. reported that the location of these HF on OCT was variable

**Figure 5.** *Long standing cystoid macular edema.*

*Optical Coherence Tomography in Diabetic Retinopathy DOI: http://dx.doi.org/10.5772/intechopen.100587*

[47]. In some cases, they were noted to be dispersed all through the retinal layers. In other cases, they were observed in the walls of microaneurysms or as confluent plaques at the level of the outer plexiform layer [47]. Bolz et al. hypothesized that the HF represented lipid deposits or precursors of hard exudates [47]. The similarity in the reflective property of HF and hard exudates supported their theory. In contrast, Lee and colleagues proposed that HF corresponded to activated microglial cells [54]. They observed a positive correlation between levels of the cytokine CD14 in the aqueous humor and the number of HF on SD-OCT in patients with DME. Cytokine CD14 is derived from activated microglial cells [55]. Microglial cells are the immune cells in the retina that undergo an inflammatory change in DR [56]. However, further studies are required to establish the origin of HF. Midena et al., described HF as dots with a size less than 30 microns, absence of back shadowing, and reflectivity similar to that of the retinal nerve fiber layer [57]. Their description allowed the distinction of HF from other hyperreflective spots on OCT such as intraretinal hemorrhage and microaneurysm. Intraretinal hemorrhage on OCT has a backshadowing effect such that retinal layers beneath the hemorrhage are not visualized. The microaneurysms on OCT have an external diameter of more than 70 microns in size [58]. Several studies reported a negative correlation between the presence of HF and visual acuity [59–62]. Uji et al. suggested a pathologic association between the presence of HF in the outer retinal layers and disruption of ELM and EZ resulting in photoreceptor dysfunction in cases with DME [59]. The presence of HF has been documented to indicate inflammatory activity or active disease status with studies reporting a significant reduction in HF after treatment with anti-VEGF and steroid implants [60, 61]. HF has also been identified as a predictor of early recurrence of DME after steroid (dexamethasone) implant [62]. HF has also been reported in DME cases that are refractory to anti-VEGF agents [63].

A characteristic arrangement of hyperreflective dots termed as pearl necklace sign in cases of DME was recently reported (**Figure 6**) [64]. It was originally described as HF surrounding the wall of a cyst located in the outer plexiform layer [64]. However, a similar appearance has recently also been described in cystoid spaces in the outer plexiform-outer nuclear layer and the inner wall of the neurosensory detachment [65]. Treatment with anti-VEGF agents in these cases led to the accumulation of hard exudates in the location of HF. A correlation of pearl necklace sign and visual acuity was only described in cases where the cyst or neurosensory detachment involved the fovea [65].

**Figure 6.** *Pearl necklace sign in a case of diabetic macular edema.*
