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Topic: The goal of this review was to summarize the current level of evidence on biomarkers to quantify diabetic retinal neurodegeneration (DRN) and diabetic macular edema (DME). Clinical relevance: With advances in retinal diagnostics, we have more data on patients with diabetes than ever before. However, the staging system for diabetic retinal disease is still based only on color fundus photographs and we do not have clear guidelines on how to incorporate data from the relatively newer modalities into clinical practice. Methods: In this review, we use a Delphi process with experts to identify the most promising modalities to identify DRN and DME. These included microperimetry, full-field flash electroretinogram, spectral-domain OCT, adaptive optics, and OCT angiography. We then used a previously published method of determining the evidence level to complete detailed evidence grids for each modality. Results: Our results showed that among the modalities evaluated, the level of evidence to quantify DRN and DME was highest for OCT (level 1) and lowest for adaptive optics (level 4). Conclusion: For most of the modalities evaluated, prospective studies are needed to elucidate their role in the management and outcomes of diabetic retinal diseases. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background:: Angelman syndrome (AS) is a severe neurodevelopmental disorder with electroencephalographic (EEG) abnormalities and sleep disturbances. It results from lack of the functional maternal allele of UBE3A, which encodes a ubiquitin–protein ligase. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity; the majority of cases of AS are due to a de novo maternal deletion of the 15q11–q13 region. Methods:: Ube3a maternal-deficient mice (Ube3a m−/p+) were generated in a C57Bl/6J background. This study compares cortical EEG and architecture of the sleep–waking cycle in adult Ube3a m−/p+ mice compared with those of age-matched WT (m+/p+) mice, under baseline conditions or after 4-h sleep deprivation (SD). Results:: Ube3a m−/p+ mice exhibited: reduced slow-wave sleep (SWS) amount with increase waking (W) at the dark/light transitions; increased SWS and W episode numbers; and deterioration of paradoxical sleep (PS) over 24 h [amount: −44%; episode duration: −46%; episode number: −40%; theta peak frequency (TPF) acceleration: 7.6 Hz vs. 7.0 Hz in WT mice]. Characteristic paroxysmal EEG discharges are observed during W and SWS associated with synchronous muscle bursting activity during hypoactive W. During the recovery period following SD, Ube3a m−/p+ mice exhibited no rebound either in slow-wave activity (+89% in WT) or in δ-power spectra but a slight rebound in PS amount (+20%). Conclusions:: These data validate the mouse model produced by null mutation of the maternal Ube3a gene and provide useful results to investigate and better understand the molecular basis of sleep disturbances in AS patients.