Purpose: The purpose of this study was to evaluate differences in optical coherence tomography angiography (OCTA) metrics in the superficial (SCP), intermediate (ICP), and deep (DCP) vascular plexuses across diabetic retinopathy (DR) severity levels. Methods: This was a cross sectional observational retrospective chart review study. Eligible patients with diabetes who underwent same day RTVue XR Avanti OCTA, spectral-domain optical coherence tomography (SD-OCT), and 200-degree Optos ultrawide field color imaging. SCP, ICP, and DCP vessel density (VD) and vessel length density (VLD) were assessed using 3-D projection artifact removal software (PAROCTA) software. Results: Of 396 eyes (237 patients), 16.1% had no DR, 26.9% mild nonproliferative DR (NPDR), 21.1% moderate NPDR, 12.1% severe NPDR, 10.1% proliferative DR (PDR) without panretinal photocoagulation (PRP), and 13.4% PDR with PRP. When comparing mild NPDR to no DR eyes, ICP and DCP VD and VLD were significantly lower, but there was no difference for SCP metrics. In eyes with more severe DR, there were significant differences in SCP VD and VLD between DR severity levels (mild versus moderate NPDR: VD 35.45 ± 3.31 vs. 34.14 ± 3.38, P = 0.008 and VLD 17.59 ± 1.83 vs. 16.80 ± 1.83, P = 0.003; moderate versus severe NPDR: VLD 16.80 ± 1.83 vs. 15.79 ± 1.84, P = 0.019), but no significant differences in ICP or DCP. Conclusions: Although VD of each of the three individual layers decreases with increasing DR severity, DR severity has a substantially different effect on OCTA parameters within each layer. Vascular changes in eyes with no to early DR were present primarily in the deeper vascular layers, whereas in eyes with advanced DR the opposite was observed. This study highlights the effects of ICP and the importance of assessing SCP and DCP changes independently across each DR severity level.

Diabetic macular oedema affects visual acuity to a varying degree. The current treatment of choice is intravitreal anti-vascular endothelial growth factor (VEGF) that has proven both its anatomical and visual efficacy in several large randomised clinical trials (RCTs). Although most patients respond well to anti-VEGF agents, some, however, show a moderate or even poor response. There is no clear consensus as to how to manage these patients, or define them. In addition, identifying early in the course of treatment which patients will respond and which patients will not is paramount to any personalised treatment regimen. Most large RCTs such as RESTORE and Protocol I have attempted post hoc analyses to identify demographic, clinical, optical coherence tomography (OCT) and fluorescein angiography findings that might predict patient response. Although some factors were found to be predictive, the lack of uniformity between the different RCTs means that no consensus exists as to which of these factors can be reliably used. This review looks at the large diabetic macular oedema RCTs such as RESTORE, Protocol I, READ-2 and BOLT in an attempt to identify common prognostic indicators between the various studies. We also attempted to look at several other OCT parameters such as the inner segment-outer segment (IS-OS) layer, the external limiting membrane layer, and choroidal thickness to help determine whether they can truly predict visual outcomes in patients being treated with anti-VEGF therapy. Finally, we provide a simplified summary about which factors might be relevant in clinical practice to help guide physicians in treatment decisions.

Purpose: To examine the relationship between ischemia and disorganization of the retinal inner layers (DRIL). Methods: Cross-sectional retrospective study of 20 patients (22 eyes) with diabetic retinopathy presenting to a tertiary academic referral center, who had DRIL on structural optical coherence tomography (OCT) using Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) and OCT angiography with XR Avanti (Optovue Inc, Fremont, CA) on the same day. Optical coherence tomography angiography images were further processed to remove flow signal projection artifacts using a software algorithm adapted from recent studies. Retinal capillary perfusion in the superficial capillary plexuses, middle capillary plexuses, and deep capillary plexuses, as well as integrity of the photoreceptor lines on OCT was compared in areas with DRIL to control areas without DRIL in the same eye. Results: Qualitative assessment of projection-resolved OCT angiography of eyes with DRIL on structural OCT demonstrated significant perfusion deficits compared with adjacent control areas (P < 0.001). Most lesions (85.7%) showed superimposed superficial capillary plexus and/or middle capillary plexus nonperfusion in addition to deep capillary plexus nonflow. Areas of DRIL were significantly associated with photoreceptor disruption (P = 0.035) compared with adjacent DRIL-free areas. Conclusion: We found that DRIL is associated with multilevel retinal capillary nonperfusion, suggesting an important role for ischemia in this OCT phenotype.

The recent VIEW studies have demonstrated the non-inferiority of monthly and bi-monthly aflibercept in the management of wet age related macular degeneration (AMD) compared with ranibizumab. However, the current data are limited mainly to fixed dosing regimens with few studies looking at flexible dosing regimens of aflibercept in wet AMD. In addition, recent data from the VIEW 96 week extension has shown that patients being shifted from fixed dosing regimens to PRN have shown a drop in visual acuity and increase in central macular thickness. This is an indication that fixed dosing, a non-sustainable option, is only effective as long as it is continued. Regimens such as treat and extend (TAE) and pro-re nata (PRN) have been studied extensively in ranibizumab and bevacizumab and have shown to be effective options. With the presence of effective, established and less costly drugs such as ranibizumab and bevacizumab, the role of aflibercept as a primary treatment modality has yet to be clearly defined. The current review provides an analysis of the VIEW studies, as well as the extension phases. It also looks at post hoc analysis of predictors of response and outcomes. We have also conducted a search on studies comparing between PRN regimens using aflibercept and other anti-VEGF agents. This review also explores cheaper off label aflibercept; ziv-aflibercept in the treatment of wet AMD. The main purpose of the review is to delineate the role of aflibercept as a primary therapeutic option and if there are any significant advantages that would advocate its use over alternative anti-VEGF drugs. Finally, we propose a treatment algorithm for patients being started on aflibercept during the first year and thereafter.

Liver kinase B1 (LKB1) is a protein kinase that activates the metabolic regulator AMP-activated protein kinase (AMPK) and other related kinases. Deletion of LKB1 in mice leads to cardiomyopathy and atrial fibrillation (AF). However, the specific role of the LKB1 pathway in early atrial biology remains unknown. Thus, we investigated whether LKB1 deletion altered atrial channel expression and electrophysiological function in a cardiomyocyte-specific knockout mouse model. We performed a systematic comparison of αMHC-Cre LKB1^fl/fl and littermate LKB1^fl/fl male mice. This included analysis of gene expression, histology, and echocardiography, as well as cellular and tissue-level electrophysiology using patch-clamp recordings in vitro, optical mapping ex vivo, and ECG recordings in vivo. At postnatal day 1, atrial depolarization was prolonged, and Na_v1.5 and Cx40 expression were markedly down-regulated in MHC-Cre LKB1^fl/fl mice. Inward sodium current density was significantly decreased in MHC-Cre LKB1^fl/fl neonatal atrial myocytes. Subsequently, additional alterations in atrial channel expression, atrial fibrosis, and spontaneous onset of AF developed by 2 weeks of age. In adult mice, abnormalities of interatrial conduction and bi-atrial electrical coupling were observed, likely promoting the perpetuation of AF. Mice with AMPK-inactivated hearts demonstrated modest overlap in channel expression with MHC-Cre LKB1^fl/fl hearts, but retained normal structure, electrophysiological function and contractility. Deletion of LKB1 causes early defects in atrial channel expression, action potential generation and conduction, which precede widespread atrial remodelling, fibrosis and AF. LKB1 is critical for normal atrial growth and electrophysiological function.