A statistically significant correlation between percentage disruption of the EZ and visual acuity was found. A convincing trend suggesting a decrease in visual acuity with increasing macular volume was documented. Percentage disruption of the EZ was recognized as an important predictor of visual acuity among DME patients (Maheshwary et al. 2010).

EZ and ELM band disruption were graded as follows (Jain et al. 2013):

Several studies have concluded that the status of ELM and EZ is closely associated with visual acuity in diabetic retinopathy (Chhablani et al. 2012; Ito et al. 2013; Ko et al. 2004; Otani et al. 2010; Shin et al. 2012). Yamauchi et al. proposed that the origin of the EZ and ELM was related to the biological activities of the photoreceptor cells. They studied the ELM and EZ in brown Norwegian rats and found that the EZ and ELM disappeared after euthanasia (Yamauchi et al. 2011). Increase in the level of severity of diabetic retinopathy results in decreased biological activity of the ELM and EZ, which in turn results in the disruption of these layers and a decrease in visual acuity.

The grade of subfoveal ELM and EZ disruption was associated with an increase in the severity of diabetic retinopathy and a decrease in visual acuity (Fig. 9.2). Global EZ disruption was associated with marked decrease in visual acuity as compared to “focal” disruption (Sharma et al. 2014).

Although the pathogenesis of diabetic retinopathy is not completely understood, several risk factors have been established. These include poor glycemic control, dyslipidemia, alteration in levels of serum urea, and serum creatinine (Ashakiran et al. 2010; Bloomgarden 2007). A number of interconnecting biochemical pathways have been proposed as potential links between hyperglycemia and diabetic retinopathy. These include increased expression of biomolecules such as vascular endothelial growth factor (VEGF), accelerated formation of advanced glycation end products (AGEs) like N-carboxy methyl lysine (N-CML), increase in oxidative stress markers, and leukostasis (Moore et al. 2003; Murata et al. 1995; Sebekova et al. 2002; Zong et al. 2011). VEGF is known to induce retinal expression of intercellular adhesion molecule-1 (ICAM-1) in turn initiating retinal leukocyte adhesion and blood-retinal barrier breakdown (Lu et al. 1999). Studies have documented a strong correlation between disruption of EZ and increase in levels of these biomolecules in diabetic retinopathy. A positive association between increasing serum levels of N-CML, VEGF, and ICAM and disruption of EZ has been reported by Saxena et al. in 2014. Disruption of EZ and ELM has been documented to have a positive association with serum levels of VEGF and ICAM by Jain et al. in 2013. Recently, a significant association between disruption of ELM and EZ with increased levels of serum cholesterol, low-density lipoprotein, and triglycerides has also been determined (Jain et al. 2015). Sharma et al. in 2015 ascertained a significant correlation between increased severity of retinopathy and increase in oxidative stress. Oxidative stress was indicated by an increase in lipid peroxidase, decrease in glutathione, and increase in nitrosative stress parameters. These studies have increased the understanding of the structural and functional alterations of the retina in diabetic retinopathy.

Each grade was then subdivided according to certain morphologic features using labels “A,” “B,” “C,” and “D.”

Presence of hyperreflective foci in the outer retinal layers from the ELM to the RPE within the 1 mm of fovea was designated with “+” signs. These hyperreflective foci represent tiny intraretinal protein and/or lipid deposits (Bolz et al. 2009). Inclusion of hyperreflective foci provide valuable information on the degree of blood-retinal barrier breakdown and its influence on visual acuity.

SD-OCT reflectivity of the ELM band was similarly analyzed. Relatively homogeneous and continuous ELM bands were described as intact. Absent or discontinuous ELM bands were described as disrupted (Murakami et al. 2012).

Few interventional studies have evaluated the role of the integrity of ELM and EZ on SD-OCT as a prognostic factor for visual outcome post-pharmacologic and surgical intervention. A statistically significant association was found between visual acuity and intact ELM and EZ post-pars plana vitrectomy with internal limiting membrane peel for DME (Yanyali et al. 2011).

Restoration of EZ and ELM was evaluated in patients with DME who were successfully treated with intravitreal triamcinolone. The integrity of EZ was found to correlate well with final visual acuity post-intervention. On multivariate analysis, the mean length of disrupted EZ and ELM band showed greater correlation to visual acuity than the length of either disrupted EZ or ELM band taken alone. The initial visual acuity (prior to treatment) and photoreceptor status both were found to assist in predicting the posttreatment recovery of EZ and subsequent visual recovery (Shin et al. 2012).