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Purpose of ReviewDiabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications.Recent FindingsThe prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well.SummaryThe American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.

Purpose of ReviewThis review offers a critical narrative evaluation of emerging evidence that sodium-glucose co-transporter-2 (SGLT2) inhibitors exert nephroprotective effects in people with type 2 diabetes.Recent FindingsThe SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes. Randomised clinical trials and ‘real world’ observational studies, mostly involving type 2 diabetes patients, have noted that use of an SGLT2 inhibitor can slow the decline in glomerular filtration rate (GFR), reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria.SummaryThe nephroprotective effects of SGLT2 inhibitors are class effects observed with each of the approved agents in people with a normal or impaired GFR. These effects are also observed in non-diabetic, lean and normotensive individuals suggesting that the mechanisms extend beyond the glucose-lowering, weight-lowering and blood pressure-lowering effects that accompany their glucosuric action in diabetes patients. A key mechanism is tubuloglomerular feedback in which SGLT2 inhibitors cause more sodium to pass along the nephron: the sodium is sensed by macula cells which act via adenosine to constrict afferent glomerular arterioles, thereby protecting glomeruli by reducing intraglomerular pressure. Other effects of SGLT2 inhibitors improve tubular oxygenation and metabolism and reduce renal inflammation and fibrosis. SGLT2 inhibitors have not increased the risk of urinary tract infections or the risk of acute kidney injury. However, introduction of an SGLT2 inhibitor in patients with a very low GFR is not encouraged due to an initial dip in GFR, and it is prudent to discontinue therapy if there is an acute renal event, hypovolaemia or hypotension.

Purpose of ReviewThe prevalence of diabetes mellitus and its chronic complications are increasing to epidemic proportions. This will unfortunately result in massive increases in diabetic distal symmetrical polyneuropathy (DPN) and its troublesome sequelae, including disabling neuropathic pain (painful-DPN), which affects around 25% of patients with diabetes. Why these patients develop neuropathic pain, while others with a similar degree of neuropathy do not, is not clearly understood. This review will look at recent advances that may shed some light on the differences between painful and painless-DPN.Recent FindingsGender, clinical pain phenotyping, serum biomarkers, brain imaging, genetics, and skin biopsy findings have been reported to differentiate painful- from painless-DPN.SummaryPainful-DPN seems to be associated with female gender and small fiber dysfunction. Moreover, recent brain imaging studies have found neuropathic pain signatures within the central nervous system; however, whether this is the cause or effect of the pain is yet to be determined. Further research is urgently required to develop our understanding of the pathogenesis of pain in DPN in order to develop new and effective mechanistic treatments for painful-DPN.

Purpose of ReviewDiabetic retinopathy (DR), the leading cause of blindness in working-aged adults, remains clinically defined and staged by its vascular manifestations. However, early retinal neurodegeneration may precede vascular pathology, suggesting that this neuronal damage may contribute to disease pathogenesis and represent an independent target for intervention. This review will discuss the evidence and implications for diabetic retinal neurodegeneration.Recent FindingsA growing body of literature has identified progressive retinal thinning and visual dysfunction in patients with diabetes even prior to the onset of DR, though advances in retinal vascular imaging suggest that vascular remodeling and choroidal changes occur during these early stages as well. Animal models of diabetes and in vitro studies have also suggested that diabetes may directly affect the retinal neural and glial tissue, providing support to the concept that diabetic retinal neurodegeneration occurs early in the disease and suggesting potentially relevant molecular pathways.SummaryDiabetic retinal neurodegeneration may represent a “preclinical” manifestation of diabetic retinal disease and remains an active area of investigation. As the natural history and molecular mechanisms become increasingly understood, it may lead to upcoming developments in not only the treatment options but also the clinical definition of DR.

Purpose of ReviewThis review highlights indications and evidence on laser therapy in the management of diabetic retinopathy and diabetic macular edema. Particular focus is placed upon the benefits and limitations of conventional laser photocoagulation versus more modern laser photocoagulation techniques, as well as the role of laser photocoagulation in treatment of diabetic retinopathy and diabetic macular edema with the frequent utilization of pharmacologic, including anti-vascular endothelial growth factor (VEGF), therapy.Recent FindingsLaser photocoagulation remains the gold-standard therapy for the effective, definitive treatment of PDR, and also is highly effective in the management of DME. However, numerous recent studies have demonstrated the clinical efficacy and improved functional and anatomic outcomes of combination therapy with pharmacologic treatment.SummaryContinuing innovations in laser technology and improved understanding of laser-retinal interactions and pathophysiology demonstrate that laser therapy will continue to play a critical role in the treatment of diabetic retinopathy and diabetic macular edema for many years to come.

Purpose of Review Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. Recent Findings Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. Summary DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.

Purpose of ReviewDiabetic foot ulcerations (DFU) affect 25% of patients with diabetes mellitus during their lifetime and constitute a major health problem as they are often recalcitrant to healing due to a constellation of both intrinsic and extrinsic factors. The purpose of this review is to (1) detail the current mechanistic understanding of DFU formation and (2) highlight future therapeutic targets.Recent FindingsFrom a molecular perspective, DFUs exhibit a chronic inflammatory predisposition. In addition, increased local hypoxic conditions and impaired cellular responses to hypoxia are pathogenic factors that contribute to delayed wound healing. Finally, recent evidence suggests a role for epigenetic alterations, including microRNAs, in delayed DFU healing due to the complex interplay between genes and the environment.SummaryIn this regard, notable progress has been made in the molecular and genetic understanding of DFU formation. However, further studies are needed to translate preclinical investigations into clinical therapies.

Purpose of ReviewIntravitreal anti-vascular endothelial growth factor (VEGF) agents are used routinely in the management of neovascular conditions including proliferative diabetic retinopathy and diabetic macular edema. While the efficacy of anti-VEGF agents has been well-validated, their ocular and systemic adverse events should always be considered and discussed with patients. The aim of this review is to discuss the most recent literature reports regarding the various ocular and systemic adverse events associated with intravitreal anti-VEGF treatment in diabetic retinopathy.Recent FindingsThe most frequently reported adverse ocular events include subconjunctival hemorrhage, vitreous hemorrhage, increased intraocular pressure, uveitis, endophthalmitis, ocular surface disease, and traumatic cataract. Subconjunctival hemorrhage and vitreous hemorrhage are the most common ocular adverse events reported with intravitreal anti-VEGF treatment. The most serious (though rare) ocular adverse events include endophthalmitis and rhegmatogenous retinal detachment. A consensus regarding the association of systemic adverse events (such as myocardial infarction, stroke, and death) with intravitreal anti-VEGF treatments has not been established.SummaryIntravitreal anti-VEGF therapy is used in the treatment of diabetic retinopathy, macular degeneration, and other diseases. These agents are associated with a variety of ocular and systemic adverse events that ophthalmologists should always consider.

Purpose of ReviewThis paper systematically reviews the recent progress in diabetic retinopathy screening. It provides an integrated overview of the current state of knowledge of emerging techniques using artificial intelligence integration in national screening programs around the world. Existing methodological approaches and research insights are evaluated. An understanding of existing gaps and future directions is created.Recent FindingsOver the past decades, artificial intelligence has emerged into the scientific consciousness with breakthroughs that are sparking increasing interest among computer science and medical communities. Specifically, machine learning and deep learning (a subtype of machine learning) applications of artificial intelligence are spreading into areas that previously were thought to be only the purview of humans, and a number of applications in ophthalmology field have been explored. Multiple studies all around the world have demonstrated that such systems can behave on par with clinical experts with robust diagnostic performance in diabetic retinopathy diagnosis. However, only few tools have been evaluated in clinical prospective studies.SummaryGiven the rapid and impressive progress of artificial intelligence technologies, the implementation of deep learning systems into routinely practiced diabetic retinopathy screening could represent a cost-effective alternative to help reduce the incidence of preventable blindness around the world.

Purpose of ReviewDiabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. Although screening and early treatment guidelines for DR have significantly reduced the disease burden, restrictions related to the COVID-19 pandemic have changed real-world practice patterns in the management of DR. This review summarizes evolving guidelines and outcomes of the treatment of DR in the setting of the pandemic.Recent FindingsIntravitreal injections for DR have decreased significantly globally during the pandemic, ranging from approximately 30 to nearly 100% reduction, compared to corresponding timepoints in 2019. Most studies on functional outcomes show a decrease in visual acuity on delayed follow-up.SummaryChanging practice patterns in the management of DR has led to fewer intravitreal injections and overall reduction in visual acuity on follow-up. As COVID variants emerge, it will be necessary to continue evaluating practice guidelines.