Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

Optimizing treatment for diabetic macular edema during cataract surgery.

Diabetic macular edema (DME) causes visual impairment in diabetic retinopathy (DR). Diabetes mellitus is a global epidemic and diabetic individuals are at risk of developing DR. Approximately 1 in 10 diabetic patients suffers from DME, which is the commonest cause of vision-threatening DR at primary-care screening. Furthermore, diabetes predisposes to a higher frequency and a younger onset of cataract, which further threatens vision in DME patients. Although cataract extraction is an effective cure, vision may still deteriorate following cataract surgery due to DME progression or recurrence, of which the risks are significantly higher than for patients without concurrent or previous history of DME at the time of operation. The management of pre-existing DME with visually significant cataract is a clinical conundrum. Deferring cataract surgery until DME is adequately treated is not ideal because of prolonged visual impairment and maturation of cataract jeopardizing surgical safety and monitoring of DR. On the other hand, the progression or recurrence of DME following prompt cataract surgery is a profound disappointment for patients and ophthalmic surgeons who had high expectations for postoperative visual improvement. Prescription of perioperative anti-inflammatory eye drops is effective in lowering the risk of new-onset DME after cataract surgery. However, management of concurrent DME at the time of cataract surgery is much more challenging because DME is unlikely to resolve spontaneously even with the aid of anti-inflammatory non-steroidal or steroid eye drops. A number of clinical trials using intravitreal injection of corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) as first-line therapy have demonstrated safety and efficacy to treat DME. These drugs have also been administered perioperatively for the prevention of DME worsening in patients undergoing cataract surgery. This article reviews the scientific evidence to guide ophthalmologists on the efficacy and safety of various therapies for managing patients with DME who are particularly vulnerable to cataract surgery-induced inflammation, which disintegrates the blood-retinal barrier and egression of fluid in macular edema.

Visualising the choriocapillaris: Histology, imaging modalities and clinical research - A review.

The choriocapillaris plays a considerable role in the normal physiology of the eye as well as in various diseases. Assessing the changes in the choriocapillaris can therefore provide important information about normal ageing and pathogenesis of visual impairment, and even some systemic diseases. In vivo imaging of the choriocapillaris has evolved from non-depth resolved, dye-based angiography to advanced, high-resolution optical coherence tomography angiography (OCTA). However, the intricate microvascular networks within the choriocapillaris are still beyond the resolving limits of most OCTA instruments. Knowledge of histology, meticulous image acquisition methods, recognition of artefact and post-acquisition processing techniques are necessary for optimising OCTA choriocapillaris images. Qualitative and quantitative analyses of the choriocapillaris provide clinical information in age-related macular degeneration (AMD), diabetic retinopathy (DR), pathologic myopia and central serous chorioretinopathy (CSC). Furthermore, studies have revealed choriocapillaris changes in posterior uveitis that are correlated with treatment outcome and have important prognostic significance. In addition to retinal diseases, choriocapillaris changes have been observed in systemic vascular diseases and complications associated with pregnancy.

Combination of Telmisartan and Linagliptin Preserves Pancreatic Islet Cell Function and Morphology in db/db Mice.

OBJECTIVES: The present study aimed to investigate the synergistic action of telmisartan and linagliptin in ameliorating pancreatic islet functions and morphology in type 2 diabetes mellitus and to delineate the molecular signaling pathway involved. METHODS: db/db mice were given telmisartan (3 mg/kg) or linagliptin (3 mg/kg) alone or in combination, daily for 8 weeks, and were studied in vivo by fasting and random blood glucose tests, oral glucose tolerance tests, and intraperitoneal insulin tolerance tests, as well as ex vivo by glucose-stimulated insulin secretion and morphology of pancreatic islets. The underlying signaling pathways were examined by Western blot, real-time quantitative polymerase chain reaction, and dihydroethidium staining analyses using mouse pancreatic islets and rat ß-insulinoma cells. RESULTS: Telmisartan/linagliptin combination induced significantly better glucose homeostasis than the monotherapies. Posttreatment reactive oxygen species level was suppressed most significantly after the telmisartan/linagliptin combined therapy, whereas no significant change in peroxisome proliferator-activated receptor γ expressions was observed after treatments. CONCLUSIONS: The telmisartan/linagliptin combination preserved pancreatic islet cell functions and morphology via reduction of oxidative stress but independent of the peroxisome proliferator-activated receptor γ pathway. Our data shed light on the therapeutic potential of using the telmisartan/linagliptin combination in the treatment of human type 2 diabetes mellitus and its related complications.

Multifaceted interplay among mediators and regulators of intestinal glucose absorption: potential impacts on diabetes research and treatment.

Glucose is the prominent molecule that characterizes diabetes and, like the vast majority of nutrients in our diet, it is absorbed and enters the bloodstream directly through the small intestine; hence, small intestine physiology impacts blood glucose levels directly. Accordingly, intestinal regulatory modulators represent a promising avenue through which diabetic blood glucose levels might be moderated clinically. Despite the critical role of small intestine in blood glucose homeostasis, most physiological diabetes research has focused on other organs, such as the pancreas, kidney, and liver. We contend that an improved understanding of intestinal regulatory mediators may be fundamental for the development of first-line preventive and therapeutic interventions in patients with diabetes and diabetes-related diseases. This review summarizes the major important intestinal regulatory mediators, discusses how they influence intestinal glucose absorption, and suggests possible candidates for future diabetes research and the development of antidiabetic therapeutic agents.

Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice.

Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.