To summarize and analyze a case of rapid progression of high-risk proliferative diabetic retinopathy after the insulin intensive therapy (IT).
A 58-year-old type 2 diabetes female patient suffered a ...rapid and dramatic decline of vision acuity in the left eye in 2 months after the insulin IT. However, the best corrected visual acuity (BCVA) of her right eye, which was in much severer condition and received panretinal photocoagulation (PRP) before, improved after the IT.
The patient received intravitreal injection of conbercept (IVC) to her left eye, and 5 days later, underwent pars plana vitrectomy (PPV), combined with PRP and silicon oil injection.
The postoperative BCVA of the left eye was 20/200 and improved to 20/160 one month later. During the subsequent 2 months of follow-up, her BCVA remained 20/160 in both eyes. Her blood glucose level also remained stable.
Insulin IT for untreated proliferative diabetic retinopathy (PDR) patients can cause severe and irreversible consequences, so for such patients, the conservative treatment for glycemic control may be much safer. But if insulin IT is inevitable, the patient should undergo PRP promptly before the IT, and close eye monitoring during the IT is also essential.
Diabetic retinopathy is one of the most common complications of diabetes mellitus and the leading cause of low vision and blindness worldwide. Mounting evidence demonstrates that inflammation is a ...key mechanism driving diabetes-associated retinal disturbance, yet the pathophysiological process and molecular mechanisms of inflammation underlying diabetic retinopathy are not fully understood. Cytokines, chemokines, and adhesion molecules interact with each other to form a complex molecular network that propagates the inflammatory and pathological cascade of diabetic retinopathy. Therefore, it is important to understand and elucidate inflammation-related mechanisms behind diabetic retinopathy progression. Here, we review the current understanding of the pathology and pathogenesis of inflammation in diabetic retinopathy. In addition, we also summarize the relevant clinical trials to further suggest inflammation-targeted therapeutics for prevention and management of diabetic retinopathy.
OBJECTIVE: To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND ...METHODS: A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS: A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS: There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.
Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent ...development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention.
To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs.
We searched several electronic databases, including CENTRAL, and trial registries. We last searched the electronic databases on 3 September 2021. We also reviewed the reference lists of review articles and trial reports selected for inclusion.
We included randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to more intense versus less intense blood pressure control; to blood pressure control versus usual care or no intervention on blood pressure (placebo); or to one class of antihypertensive medication versus another or placebo.
Pairs of review authors independently reviewed the titles and abstracts of records identified by the electronic and manual searches and the full-text reports of any records identified as potentially relevant. The included trials were independently assessed for risk of bias with respect to outcomes reported in this review.
We included 29 RCTs conducted in North America, Europe, Australia, Asia, Africa, and the Middle East that had enrolled a total of 4620 type 1 and 22,565 type 2 diabetic participants (sample sizes from 16 to 4477 participants). In all 7 RCTs for normotensive type 1 diabetic participants, 8 of 12 RCTs with normotensive type 2 diabetic participants, and 5 of 10 RCTs with hypertensive type 2 diabetic participants, one group was assigned to one or more antihypertensive agents and the control group to placebo. In the remaining 4 RCTs for normotensive participants with type 2 diabetes and 5 RCTs for hypertensive type 2 diabetic participants, methods of intense blood pressure control were compared to usual care. Eight trials were sponsored entirely and 10 trials partially by pharmaceutical companies; nine studies received support from other sources; and two studies did not report funding source. Study designs, populations, interventions, lengths of follow-up (range less than one year to nine years), and blood pressure targets varied among the included trials. For primary review outcomes after five years of treatment and follow-up, one of the seven trials for type 1 diabetics reported incidence of retinopathy and one trial reported progression of retinopathy; one trial reported a combined outcome of incidence and progression (as defined by study authors). Among normotensive type 2 diabetics, four of 12 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; two trials reported combined incidence and progression. Among hypertensive type 2 diabetics, six of the 10 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; five of the 10 trials reported combined incidence and progression. The evidence supports an overall benefit of more intensive blood pressure intervention for five-year incidence of diabetic retinopathy (11 studies; 4940 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.73 to 0.92; I
= 15%; moderate certainty evidence) and the combined outcome of incidence and progression (8 studies; 6212 participants; RR 0.78, 95% CI 0.68 to 0.89; I
= 42%; low certainty evidence). The available evidence did not support a benefit regarding five-year progression of diabetic retinopathy (5 studies; 5144 participants; RR 0.94, 95% CI 0.78 to 1.12; I
= 57%; moderate certainty evidence), incidence of proliferative diabetic retinopathy, clinically significant macular edema, or vitreous hemorrhage (9 studies; 8237 participants; RR 0.92, 95% CI 0.82 to 1.04; I
= 31%; low certainty evidence), or loss of 3 or more lines on a visual acuity chart with a logMAR scale (2 studies; 2326 participants; RR 1.15, 95% CI 0.63 to 2.08; I
= 90%; very low certainty evidence). Hypertensive type 2 diabetic participants realized more benefit from intense blood pressure control for three of the four outcomes concerning incidence and progression of diabetic retinopathy. The adverse event reported most often (13 of 29 trials) was death, yielding an estimated RR 0.87 (95% CI 0.76 to 1.00; 13 studies; 13,979 participants; I
= 0%; moderate certainty evidence). Hypotension was reported in two trials, with an RR of 2.04 (95% CI 1.63 to 2.55; 2 studies; 3323 participants; I
= 37%; low certainty evidence), indicating an excess of hypotensive events among participants assigned to more intervention on blood pressure.
Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.
To estimate global and regional trends from 1990 to 2010 of the prevalence and number of persons visually impaired specifically by diabetic retinopathy (DR), as a complication of the precipitous ...trends in global diabetes, is fundamental for health planning purposes.
The meta-analysis of published population studies from 1990 to 2012 for the Global Burden of Disease Study 2010 (GBD) yielded estimated global regional trends in DR among other causes of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60).
Globally in 2010, out of overall 32.4 million blind and 191 million visually impaired people, 0.8 million were blind and 3.7 million were visually impaired because of DR, with an alarming increase of 27% and 64%, respectively, spanning the two decades from 1990 to 2010. DR accounted for 2.6% of all blindness in 2010 and 1.9% of all MSVI worldwide, increasing from 2.1% and 1.3%, respectively, in 1990. These figures were lower in regions with younger populations (<2% in East and Southeast Asia and Oceania) than in high-income regions (North America, Western Europe, and Australasia) with relatively aging populations (>4%).
The number of persons with visual impairment due to DR worldwide is rising and represents an increasing proportion of all blindness/MSVI causes. Age-standardized prevalence of DR-related blindness/MSVI was higher in sub-Saharan Africa and South Asia. One out of 39 blind people had blindness due to DR, and 1 out of 52 visually impaired people had visual impairment due to DR.
To compare optical coherence tomography (OCT) angiographic parameters in retina and choriocapillaris between control subjects and diabetic patients without diabetic retinopathy (NDR). Correlations ...were studied between OCT angiography parameters, retinal structure parameters, and systemic characteristics in all subjects.
Sixty-two patients were included in the study: control subjects (n = 33) and patients with NDR (n = 29). Optical coherence topography angiographic parameters were as follows: vessel density (%) (in superficial, deep retinal vessel plexus and in choriocapillary layer) and foveal avascular zone (FAZ) area (mm2) in superficial and deep retinal vessel plexus of parafovea. Split-spectrum amplitude decorrelation angiography (SSADA) software algorithm was used for evaluation of vessel density and FAZ area (nonflow area tool). Spectral-domain OCT was used to assess full, inner, and outer retinal thickness and volume in parafovea.
In superficial and deep retina, vessel densities in NDR (44.35% ± 13.31% and 31.03% ± 16.33%) were decreased as compared to control subjects (51.39% ± 13.05%, P = 0.04; and 41.53% ± 14.08%, P < 0.01). Foveal avascular zone in superficial retina of NDR patients (0.37 ± 0.11 mm2) was greater than in controls (0.31 ± 0.10 mm2, P = 0.02). Superficial vessel density significantly correlated with full retinal thickness and volume in parafovea (r = 0.43, P = 0.01; r = 0.43, P = 0.01) and with outer retinal volume in parafovea (r = 0.35, P < 0.05) of healthy subjects. Systolic blood pressure and ocular perfusion pressure significantly correlated with deep vessel density in NDR (r = -0.45, P = 0.02; r = -0.46, P = 0.01), but not in controls.
Superficial and deep retinal vessel density in parafovea of diabetic patients without diabetic retinopathy are both decreased compared to healthy subjects. The associations between vessel density with retinal tissue thickness and with subject's clinical characteristics differ between healthy subjects and patients with NDR.
To analyze the morphological characteristics and long-term visual outcomes in eyes with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with anti−vascular endothelial growth factor ...(anti-VEGF) therapy.
Retrospective clinical cohort study.
Patients with a long-term follow-up and evidence of resolved DME in at least 1 visit (study visit) after 5 years of follow-up after the initiation of anti-VEGF therapy were included. At the study visit, structural optical coherence tomography (OCT) scans were reviewed for qualitative features reflecting a distress of the neuroretina or retinal pigment epithelium (RPE). A quantitative topographical assessment of the inner and outer retinal thicknesses was also provided.
A total of 61 eyes (50 patients) were included and were divided into 2 subgroups according to visual acuity (VA) at the study visit, yielding a group of 24 eyes with a VA <20/40 (“poor/intermediate vision” group), and 37 eyes with a VA ≥20/40 (“good vision” group). The external limiting membrane (ELM) and RPE bands were more frequently disrupted or absent in the poor/intermediate vision group (P = .003 and P = .019). Similarly, disorganization of retinal inner layers was more prevalent in the poor/intermediate vision group (P = .013). The foveal and parafoveal outer retinal thicknesses were reduced in eyes with poor/intermediate vision (P = .022 and P = .044). Multivariate stepwise linear regression analysis demonstrated that VA was associated with appearances of the RPE and ELM (P < .0001 and P = .048), foveal and parafoveal outer retinal thicknesses (P = .046 and P = .035).
Modifications in the outer retina and RPE represent OCT biomarkers of long-term visual outcomes in eyes with DME treated with anti-VEGF.
Previous studies have reported that endothelial-to-mesenchymal transition (EndoMT) contributes to pathological fibrosis in proliferative diabetic retinopathy (PDR). The hypothesis of our study was ...that exosomes from high glucose (HG)-treated ARPE19 cells reprogram endothelial cell behavior in HG conditions by transferring their genetic contents. Our study showed that ARPE19-derived exosomes were internalized by human umbilical vein endothelial cells (HUVECs). Additionally, miR-202-5p, a miRNA known to target TGFβR2, was enriched in ARPE19-derived exosomes. A dual luciferase reporter assay, qPCR, and western blotting were used to characterize the expression of miR-202-5p and phosphorylation of the TGF/Smad pathway proteins. We showed that miR-202-5p-containing exosomes suppressed HUVEC cell growth, migration, and tube formation. Furthermore, TGFβR2 was confirmed as the target of miR-202-5p. A dual luciferase reporter assay showed that TGFβR2 expression was negatively regulated by miR-202-5p. We also showed that miR-202-5p-containing exosomes suppressed HG-induced EndoMT. These collective results suggested that ARPE-derived exosomes may serve as significant mediators of cell-to-cell crosstalk to suppress EndoMT by transferring miR-202-5p through the TGF/Smad pathway, and may be a potential treatment for PDR patients.
•ARPE19 cells release exosomes in high glucose condition.•Exosomes from high glucose treated ARPE19 cells modulate phenotypes of HUVECs.•Exosomal miR-202-5p regulates the TGFβ signaling pathway by targeting TGFβR2.
Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is ...characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. The number of DR patients is growing with an increase in the elderly population, and therapeutic approaches are limited, therefore, new therapies to prevent retinal injury and enhance repair are a critical unmet need. Besides vascular endothelial growth factor (VEGF)-induced vascular proliferation, several other mechanisms are important in the pathogenesis of diabetic retinopathy, including vascular inflammation. Thus, combining anti-VEGF therapy with other new therapies targeting these pathophysiological pathways of DR may further optimize treatment outcomes. Technological advancements have allowed for high-throughput proteomic studies examining biofluids such as aqueous humor, vitreous humor, tear, and serum. Many DR biomarkers have been identified, especially proteins involved in retinal inflammatory processes. This review attempts to summarize the proteomic biomarkers of DR-associated retinal inflammation identified over the last several years.
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