RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
DESIGN: Secondary analysis on Malaysian Cataract Surgery Registry data.
METHODS: The Malaysian Cataract Surgery Registry, a MOH-initiated registry, collects data on patients who had cataract surgery at the 36 MOH ophthalmology departments including demography, causes of cataract, systemic and ocular comorbidity, preoperative visual acuity (VA), operative details, and postoperative outcomes. This article reviews data on patient profiles from 2002 to 2004 and 2007 to 2011.
RESULTS: The coverage of cataract surgery was 91.5% (171,482/185,388). Mean patient age was 64.5 years, and 51.6% were women. A high proportion of patients had hypertension (48.9%), diabetes mellitus (37.1%), and diabetic retinopathy (10.7%). Most had senile cataract (93.4%) and one third had second eye surgery. Most patients (82.0%) had preoperative unaided VA of worse than 6/12. Eyes presenting with unaided VA of worse than 3/60 decreased from 62.6% in 2002 to 47.7% in 2011, whereas those with 6/18 to 3/60 increased from 35.2% to 48.5% (P < 0.001). Patients who had extracapsular cataract extraction had worse preoperative VA than those who had phacoemulsification (81.3% vs 40% had vision worse than 3/60).
CONCLUSIONS: The obvious change in patient profiles was the decreasing number of eyes presenting with worse than 3/60 vision. Compared with developed countries, patients who had cataract surgery at MOH hospitals in Malaysia were younger and had higher associations with diabetes mellitus and diabetic retinopathy.
DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide.
METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation.
RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed.
CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.