MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation.

PURPOSE: This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. METHODS: In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism. RESULTS: In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEVmiR-22-3p(-) on AGEs-induced microglia was compromised, as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV. CONCLUSION: These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.

Pericyte in retinal vascular diseases: A multifunctional regulator and potential therapeutic target.

Retinal vascular diseases (RVDs), in particular diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity, are leading contributors to blindness. The pathogenesis of RVD involves vessel dilatation, leakage, and occlusion; however, the specific underlying mechanisms remain unclear. Recent findings have indicated that pericytes (PCs), as critical members of the vascular mural cells, significantly contribute to the progression of RVDs, including detachment from microvessels, alteration of contractile and secretory properties, and excessive production of the extracellular matrix. Moreover, PCs are believed to have mesenchymal stem properties and, therefore, might contribute to regenerative therapy. Here, we review novel ideas concerning PC characteristics and functions in RVDs and discuss potential therapeutic strategies based on PCs, including the targeting of pathological signals and cell-based regenerative treatments.

Clinical-grade human embryonic stem cell-derived mesenchymal stromal cells ameliorate diabetic retinopathy in db/db mice.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) hold great promise in the treatment of diabetic retinopathy (DR), as evidenced by increasing preclinical and clinical studies. However, the absence of standardized and industrialized clinical-grade donor cells hampers the continued development and large-scale clinical application of MSCs-based therapies for DR. Previously, we have identified a unique population of MSCs generated from a clinical-grade human embryonic stem cell (hESC) line under Good Manufacturing Practice conditions that could be a potential source to address the issues. Here, we investigated the therapeutic potential of the clinical-grade hESC line-derived MSCs (hESC-MSCs) on db/db mice with DR. METHODS: hESC-MSCs were initially characterized by morphological assessment, flow cytometry analysis and trilineage differentiation assays. These cells (5 × 106 cells) were then transplanted intravenously into 12-week-old db/db mice via tail vein, with phosphate-buffered saline transplantation and untreated groups used as controls. The retinal alterations in neural functions and microvascular perfusions, and inflammatory responses in peripheral blood and retina were evaluated at 4 and 6 weeks after transplantation using electroretinography, optical coherence tomography angiography and flow cytometry, respectively. Body weight and fasting blood glucose (FBG) levels were also measured to investigate their systemic implications. RESULTS: Compared with controls, intravenous transplantation of hESC-MSCs could significantly: (i) enhance impaired retinal electroretinography functions (including amplitudes of a-, b-wave and oscillatory potentials) at 4 weeks after transplantation; (ii) alleviate microvascular dysfunctions, especially in the inner retina with significance (including reducing non-perfusion area and increasing vascular area density) at 4 weeks after transplantation; (iii) decrease FBG levels at 4 weeks after transplantation and induce weight loss up to 6 weeks after transplantation and (iv) increase both peripheral blood and retinal interleukin-10 levels at 4 weeks after transplantation and modulate peripheral blood inflammatory cytokines and chemokines levels, such as monocyte chemotactic protein-1, up to 6 weeks after transplantation. CONCLUSIONS: The findings of our study indicated that intravenous transplantation of hESC-MSCs ameliorated retinal neural and microvascular dysfunctions, regulated body weight and FBG and modulated peripheral blood and retinal inflammation responses in a mouse model of DR. These results suggest that hESC-MSCs could be a potentially effective clinical-grade cell source for the treatment of DR.

A nonparametric relative treatment effect for direct comparisons of censored paired survival outcomes.

A frequently addressed issue in clinical trials is the comparison of censored paired survival outcomes, for example, when individuals were matched based on their characteristics prior to the analysis. In this regard, a proper incorporation of the dependence structure of the paired censored outcomes is required and, up to now, appropriate methods are only rarely available in the literature. Moreover, existing methods are not motivated by the strive for insights by means of an easy-to-interpret parameter. Hence, we seek to develop a new estimand-driven method to compare the effectiveness of two treatments in the context of right-censored survival data with matched pairs. With the help of competing risks techniques, the so-called relative treatment effect is estimated. This estimand describes the probability that individuals under Treatment 1 have a longer lifetime than comparable individuals under Treatment 2. We derive hypothesis tests and confidence intervals based on a studentized version of the estimator, where resampling-based inference is established by means of a randomization method. In a simulation study, we demonstrate for numerous sample sizes and different amounts of censoring that the developed test exhibits a good power. Finally, we apply the methodology to a well-known benchmark data set from a trial with patients suffering from diabetic retinopathy.

The role of cadre in the community on diabetic retinopathy management and its challenges in low-middle income countries: a scoping review.

INTRODUCTION: Diabetes is a serious public health problem, with low- and middle-income countries (LMICs) bearing over 80% of the burden. Diabetic retinopathy (DR) is one of the most prevalent diabetic microvascular problems, and early diagnosis through eye screening programs for people with diabetes is critical to prevent vision impairment and blindness. Community-based treatments, including non-physician cadres have been recommended to enhance DR care. METHODS: The review protocol was determined and scoping review was conducted.The population, concept, and context were "cadre", "role of cadre in the management of DR", and LMICs". Data were collected from databases and searches, including grey literature. RESULTS: Cadre can motivate people to attend a diabetic eye screening event when the rate of eye examinations is about six times higher than before the start of the intervention. Health education is a possible area for task sharing, and the cadre reported could also perform the task of vision testing. The cadre could be a good supporter and a good reminder for society. However, several challenges have been faced in this study and inadequate infrastructure is the foremost challenge found in this study. Other challenges encountered in the studies include poverty, lack of community awareness, trust issues, and low education levels contributing to poor health. CONCLUSION: The current study highlighted significant gaps in the literature, which focus on the role of cadre as a community-based intervention in managing DR in LMICs. Further research is needed to develop evidence to support cost-effective screening services and cadre-related policy development in LMICs.

Structured Counselling and Regular Telephonic follow up to improve Referral flow and compliance in Nepal for Diabetic Retinopathy(SCREEN-D Study): a randomised controlled trial.

BACKGROUND: Diabetic Retinopathy (DR) is an emerging public health issue, leading to severe visual impairment or blindness. Early identification and prompt treatment play a key role in achieving good visual outcomes. The objective of the study was to estimate the effectiveness of SCREEN package on improving referral compliance from peripheral centres to a tertiary eye centre in Nepal. METHODS: In this facility-based cluster-randomized trial, ten out of 19 referring centres of the tertiary eye care centre in Lumbini zone, Nepal were randomized into intervention and control groups. A SCREEN packagewereprovided as intervention for DR patients who require advanced treatment in the tertiary centres and was compared with the current practice of the control arm, where structured counselling and follow-up mechanism are absent. Compliance was estimated by a weekly follow-up between the referring centre and the referred hospital. RESULTS: We recruited 302 participantsof whom 153 were in the intervention arm. The mean age of the participants was 57.8 years (Standard deviation [SD]±11.7 years). With implementation of SCREEN package71.2% (n=109) in the intervention group and 42.9% (n=64) in the control group were compliant till three months of follow-up (Difference 28.3%, 95% CI: 17.6- 39.0, p<0.05). Compliance was 43% (n=66) with counselling alone, and 66% (n=103) with first telephonic follow-up in the intervention arm. The mean duration to reach the referral centre was 14.7 days (SD± 9.4 days) and 18.2 days (SD± 9.1 days) in the intervention and the control arm, respectively (Difference 3.5 days, 95% CI: 0.7 to 6.4 days). CONCLUSIONS: Counselling& follow-up to patients is the key factor to improve the utilization of the health services by patients with DR. Health systems must be strengthened by optimizing the existing referral structure in Nepal. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration and Results System, ClinicalTrials.gov Identifier: NCT04834648 , 08/04/2021.

Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy.

The blood-retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A2 activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs. The data obtained highlighted the potential of autologous differentiated ASCs in future clinical applications based on cell therapy to counteract the damage induced by DR.

[Biomechanics of diabetic vitreopapillary traction syndrome]. / Biomekhanika diabeticheskogo vitreopapillyarnogo traktsionnogo sindroma.

Diabetic vitreopapillary traction syndrome (VPT) is a variant of diabetic retinopathy (DR) that can lead to vision loss in advanced stages. This review reports on the biomechanics of the vitreous in the pathogenesis of proliferative DR, in particular diabetic VPT. The article analyzes and summarizes literature data, presents the views of different authors on this problem, and provides the results of Russian and foreign scientific research on this pathology. It is concluded that further research in this area can lead to a significant improvement in the results of therapy, timely diagnosis, and preservation of vision in patients with DR.

Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept.

PURPOSE: To compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. METHODS: This study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. RESULTS: During a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). CONCLUSION: The aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

The effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy in type II diabetes mellitus patients: A clinical trial.

INTRODUCTION: Diabetic retinopathy (DR) is one of the most threatening complications of diabetes and a leading cause of visual loss in working-age population. Although exercise is beneficial in diabetes, previous studies have showed contradictory and inconclusive results on how it effects DR. In this study, we aimed to investigate the effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy. MATERIALS & METHODS: In this before-after clinical trial, 40 patients with diabetic retinopathy were enrolled by convenient sampling method in Shahid Labbafinejad Hospital in Tehran during 2021-2022. Before the intervention, central macular thickness (CMT, microns) measured by optical coherence tomography (OCT) and fasting blood sugar (FBS, mg/dl) were obtained. Then, patients took part in a 12-week moderate-intensity aerobic exercise (3 sessions per week, each session 45 min). Data were analyzed using SPSS version 26.0. RESULTS: Out of 40 examined patients, 21 (52.5 %) were male and 19 (47.5 %) were female. The mean age of the patients was 50.8 years. The mean rank of FBS (mg/dl) significantly decreased from 21.12 before the exercise to 8.75 after the exercise (p < 0.001). Also, the mean rank of CMT (microns) showed a significant decrease from 21.11 before the intervention to 16.20 after the exercise (p < 0.001). There was a significant positive correlation between patients' age and FBS (mg/dl) before (rho = 0.457, p = 0.003) and after (rho = 0.365, p = 0.021) the intervention. Also, a significant positive correlation was found between patients' age and CMT (microns) before (rho = 0.525, p = 0.001) and after (rho = 0.461, p = 0.003) moderate exercise. CONCLUSION: Moderate-intensity aerobic exercise leads to lower FBS (mg/dl) and CMT (microns) in patients with diabetic retinopathy, so it may be beneficial for diabetic patients to avoid sedentary lifestyle.

Enablers and barriers to diabetic retinopathy eye care among first nations and Métis women.

BACKGROUND: Diabetes is increasingly prevalent in Indigenous women and increases their risk of developing diabetic retinopathy, an eye complication of diabetes and a common cause of vision loss in Canada, especially among adults. Early detection is the most effective approach to prevent vision loss and reduce the impact of diabetic retinopathy. OBJECTIVE: This study examined enablers and barriers that influence the diabetes eye care behaviour of First Nations and Métis women with diabetes and at risk of diabetes. METHODS: We conducted a descriptive qualitative study with 35 First Nations and Métis women with diabetes or at risk of diabetes in Saskatoon, Canada. Data were collected via four sharing circle discussions and were analysed using thematic analysis. RESULTS: The study findings showed that understanding of diabetes eye care access and cost, and unsupportive interactions with health care practitioners, were barriers to diabetic retinopathy care behaviour. Conversely, the presence of eye complications, participants' resolve to manage diabetes, self-efficacy and fear due to experiences of family members with diabetes enabled diabetes eye care. CONCLUSIONS: Our study advances knowledge in socio-cultural factors influencing diabetic retinopathy care behaviour among First Nations and Métis women living with and at risk of diabetes. The study shows the need for further public health and health system interventions to address barriers and support Indigenous peoples with or at risk of diabetes to make informed health decisions.

Diabetic retinopathy in the pediatric population: Pathophysiology, screening, current and future treatments.

Diabetic retinopathy (DR) is a sight threatening complication of diabetes mellitus (DM). The incidence of DR in the pediatric population has increased in the last two decades and it is expected to further rise in the future, following the increase in DM prevalence and obesity in youth. As early stages of the retinal disease are asymptomatic, screening programs are of extreme importance to guarantee a prompt diagnosis and avoid progression to more advanced, sight threatening stages. The management of DR comprises a wide range of actions starting from glycemic control, continuing with systemic and local medical treatments, up to para-surgical and surgical approaches to deal with the more aggressive complications. In this review we will describe the pathophysiology of DR trying to understand all the possible targets for currently available or future treatments. We will briefly consider the impact of screening techniques, screening strategies and their social and economic impact. Finally a large part of the review will be dedicated to medical and surgical treatments for DR including both currently available and under development therapies. Most of the available data in the literature on DR are focused on the adult population. The aim of our work is to provide clinicians and researchers with a comprehensive overview of the state of the art regarding DR in the pediatric population, considering the increasing numbers of this diseases in youth and the inevitable consequences that such a chronic disease could have if poorly managed in children.

Stem cells and diabetic retinopathy: From models to treatment.

Diabetic retinopathy is a common yet complex microvascular disease, caused as a complication of diabetes mellitus. Associated with hyperglycemia and subsequent metabolic abnormalities, advanced stages of the disease lead to fibrosis, subsequent visual impairment and blindness. Though clinical postmortems, animal and cell models provide information about the progression and prognosis of diabetic retinopathy, its underlying pathophysiology still needs a better understanding. In addition to it, the loss of pericytes, immature retinal angiogenesis and neuronal apoptosis portray the disease treatment to be challenging. Indulged with cell loss of both vascular and neuronal type cells, novel therapies like cell replacement strategies by various types of stem cells have been sightseen as a possible treatment of the disease. This review provides insight into the pathophysiology of diabetic retinopathy, current models used in modelling the disease, as well as the varied aspects of stem cells in generating three-dimensional retinal models. Further outlook on stem cell therapy and the future directions of stem cell treatment in diabetic retinopathy have also been contemplated.

Recent advances in the management of proliferative diabetic retinopathy.

PURPOSE OF REVIEW: The prevalence of diabetic retinopathy continues to rise. This review highlights advances in imaging, medical, and surgical management of proliferative diabetic retinopathy (PDR) in recent years. RECENT FINDINGS: Ultra-widefield fluorescein angiography has been shown to better characterize which patients have predominantly peripheral lesions and who may advance to more advanced forms of diabetic retinopathy. This was well demonstrated in DRCR Retina Network's Protocol AA. Protocol S demonstrated that antivascular endothelial growth factor (VEGF) treatment alone can be useful in the management of select PDR patients - particularly those without high-risk features. However, a growing body of literature highlights how lapse in care is a significant concern in PDR patients, and tailoring one's approach to treatment based on patient needs is recommended. In patients with high-risk features or where there is concern for lost-to-follow-up, incorporation of panretinal photocoagulation in the treatment paradigm is recommended. Protocol AB highlighted how patients with more advanced disease may benefit from earlier surgical intervention for earlier visual recovery but that continued anti-VEGF treatment may result in similar visual outcomes over a longer period. Finally, earlier surgical intervention for PDR without vitreous hemorrhage (VH) or retinal detachment is being considered a potential option to minimize treatment burden. SUMMARY: Recent advances in imaging, as well as medical and surgical treatment options for PDR, have provided a deeper understanding of PDR management, which can be optimized for the individual patient.

Understanding the behavioral determinants that predict barriers and enablers of screening and treatment behaviors for diabetic retinopathy among Bangladeshi women: findings from a barrier analysis.

BACKGROUND AND AIM: While early detection and timely treatments can prevent diabetic retinopathy (DR) related blindness, barriers to receiving these DR services may cause permanent sight loss. Despite having similar prevalence to diabetes and DR, women are less likely than men to perform these behaviors due to multi-faced barriers in screening and receiving follow-up treatments for DR. This study, therefore, aimed at identifying the barriers to - and enablers of - screening and follow-up treatments behaviors for DR among women aged more than 40 years with diabetes from the behavioral perspectives in Bangladesh. METHODS: This Barrier Analysis study interviewed 360 women (180 "Doers" and 180 "Non-doers") to explore twelve behavioral determinants of four DR behaviors including screening, injection of anti-vascular endothelial growth factor (anti-VEGF medication), laser therapy and vitro-retinal surgery. The data analysis was performed to calculate estimated relative risk to identify the degree of association between the determinants and behaviors, and to find statistically significant differences (at p < 0.05) in the responses between the Doers and Non-doers. RESULTS: Access to healthcare facilities was the major barrier impeding women from performing DR behaviors. Difficulty in locating DR service centers, the need to travel long distances, the inability to travel alone and during illness, challenges of paying for transportation and managing workload significantly affected women's ability to perform the behaviors. Other determinants included women's perceived self-efficacy, perceived negative consequences (e.g. fear and discomfort associated with injections or laser treatment), and cues for action. Significant perceived enablers included low cost of DR treatments, supportive attitudes by healthcare providers, government policy, and perceived social norms. CONCLUSION: The study found a host of determinants related to the barriers to and enablers of DR screening and treatment behaviors. These determinants included perceived self-efficacy (and agency), positive and negative consequences, perceived access, perceived social norms, culture, and perceived risk. Further investments are required to enhance the availability of DR services within primary and secondary health institutions along with health behavior promotion to dispel misconceptions and fears related to DR treatments.

Effectiveness and Financial Viability of Telehealth Physician Extenders for Re-Engagement of Patients with Diabetic Retinopathy.

Purpose: To assess the effectiveness and financial implications of employing a telehealth physician extender program to re-engage patients with diabetic retinopathy (DR) who are lost to follow-up (LTF). Methods: Established patients with DR unevaluated in the prior 12 months were identified as LTF, and randomized to receive a recall intervention or standard operating procedure (SOP). For the intervention, a telehealth physician extender performed outbound calls, offering each patient a symptom screening questionnaire following a physician-directed escalation pathway and assistance in scheduling a return appointment. All patients retained the ability to schedule an appointment by means of SOP. Appointment schedule and adherence rates were assessed 30 days after a 6-week intervention period. Call times were digitally measured to estimate intervention labor cost. Results: Four hundred twenty-five of 2,514 established patients with DR were LTF (17%). One hundred fifty-seven patients were assigned to the intervention group; the remaining 268 formed the SOP group. Sixty-six outbound calls reached patients (42%). At the time of program assessment, the intervention group demonstrated a higher rate of appointment scheduling (31% vs. 14%, p < 0.001) and adherence (14% vs. 7%, p = 0.020). The measured call duration was 2.3 ± 1.9 min, yielding an estimated cost of US$4.70 per appointment scheduled. Conclusion: Re-engagement by a telehealth physician extender improves the rate at which patients with DR return for eye care, and can be done at a reasonable cost. This method of improving adherence with follow-up should be readily translatable to other health care settings.

The Role of Inflammation and Therapeutic Concepts in Diabetic Retinopathy-A Short Review.

Diabetic retinopathy (DR) as a microangiopathy is the most common complication in patients with diabetes mellitus (DM) and remains the leading cause of blindness among adult population. DM in its complicated pathomechanism relates to chronic hyperglycemia, hypoinsulinemia, dyslipidemia and hypertension-all these components in molecular pathways maintain oxidative stress, formation of advanced glycation end-products, microvascular changes, inflammation, and retinal neurodegeneration as one of the key players in diabetes-associated retinal perturbations. In this current review, we discuss the natural history of DR with special emphasis on ongoing inflammation and the key role of vascular endothelial growth factor (VEGF). Additionally, we provide an overview of the principles of diabetic retinopathy treatments, i.e., in laser therapy, anti-VEGF and steroid options.

Diabetic Retinopathy - a Common Disease. / Volkskrankheit diabetische Retinopathie.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and one of the leading causes of visual impairment in working age individuals in the western world. The treatment of DR depends on its severity, so it is of great importance to detect patients as early as possible, in order to initiate early treatment and preserve vision. Despite currently insufficient screening participation, patients with diabetes already visit ophthalmological practices and clinics above average. Their medical care, including DR diagnostics and treatment has been making up an increasing proportion of ophthalmic activity for years. Since the prevalence of diabetes is increasing dramatically worldwide and a further increase is also predicted for Germany, the challenge for ophthalmologists is likely to grow considerably. As the same time, the diagnostic possibilities for differentiating DR and the therapeutic measures, especially with IVOM therapy, are becoming more and more complex, which increases the time burden in everyday clinical practice. The hope to avoid healthcare deficits and to further improve screening rates and visual acuity prognosis in patients with DR is based, among other things, on camera-assisted screening supported by artificial intelligence. Better diabetes management to reduce the prevalence of DR, as well as longer-acting drugs to treat DR, could also improve the care and help reduce the burden on ophthalmology practices.

Identifying best-practice features of diabetic retinopathy treatment models for Aboriginal and Torres Strait Islander Australians.

OBJECTIVE: Indigenous Australians are nearly three times more likely to have diabetes than non-Indigenous Australians. The prevalence of diabetes-related vision impairment for Indigenous Australians is 5.5% compared to 1.5% for non-Indigenous Australians, and treatment rates are lower for Indigenous Australians. Despite this situation, there is limited evidence on effective service delivery models for diabetic retinopathy care and treatment. This study seeks to identify best-practice features of diabetic retinopathy care that could be used to inform current and future service delivery models for Indigenous Australians with diabetic retinopathy. SETTING: All states, territories and geographic remoteness categories in Australia. PARTICIPANTS: Eight ophthalmologists engaged in providing eye healthcare to Indigenous Australians. DESIGN: Semi-structured interviews were conducted. The Framework Approach was used to conduct a thematic analysis of the interviews to facilitate identification of key themes and issues that emerged from these discussions. RESULTS: Seven best-practice features for service delivery of diabetic retinopathy treatment for Indigenous Australians were identified. These were: cultural safety, affordability and accessibility, partnerships with key stakeholders, timeliness, integration with primary care, clarity of guidelines, and clinician attitude and motivation. CONCLUSION: The findings from this study identified seven best-practice features for diabetic retinopathy treatment. These have the potential to inform and influence how care is delivered to Indigenous Australians. Although further research is warranted to capture other service provider inputs and Indigenous end-user perspectives, these features in the meantime can begin to inform the decisions of the Indigenous eyecare sector on policy reforms and best-practice diabetic retinopathy treatment approaches.

Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review.

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.