sirolimus and Diabetic-Retinopathy

Pathological ocular angiogenesis is a causative factor of retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. Vascular endothelial growth factor (VEGF) plays an important role in pathological angiogenesis, and anti-VEGF agents have been used to treat the ocular diseases that are driven by pathological angiogenesis. However, adverse effects associated with the blockade of VEGF signaling, including impairments of normal retinal vascular growth and retinal function, were suggested. Therefore, the development of a safe, effective strategy to prevent pathological ocular angiogenesis is needed. Recent studies have demonstrated that inhibitors of the mammalian target of rapamycin (mTOR) target proliferating endothelial cells within the retinal vasculature. Here, we review the potential of targeting the mTOR pathway to treat pathological ocular angiogenesis.

Topics: Angiogenesis Inhibitors; Animals; Choroid; Cornea; Diabetic Retinopathy; Disease Models, Animal; Endothelial Cells; Humans; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Retina; Retinal Neovascularization; Retinal Vessels; Signal Transduction; Sirolimus; Vascular Endothelial Growth Factor A

In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high-risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.

Topics: Albuminuria; Child; Cyclosporine; Diabetes Mellitus; Diabetic Retinopathy; Glucocorticoids; Humans; Hyperlipidemias; Hypertension; Immunosuppressive Agents; Insulin; Liver Failure; Liver Transplantation; Metformin; Pediatrics; Risk Factors; Sirolimus; Tacrolimus

To evaluate the safety and tolerability of a single subconjunctival (SCJ) or intravitreal (IVT) injection of an ophthalmic sirolimus formulation in eyes with diabetic macular edema (DME).. Randomized, open-label, dose-escalating phase I study.. Fifty eyes among 50 patients with DME, retinal thickness ≥ 300 microns and best-corrected visual acuity (BCVA) 20/40 to 20/200.. A single dose of sirolimus administered SCJ (220, 440, 880, 1320, or 1760 μg) or IVT (44, 110, 176, 264, or 352 μg) on day 0; observation through day 90.. Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were changes in BCVA and retinal thickness.. No dose-limiting toxicities were observed and ocular adverse events were mostly mild and transient. Conjunctival hyperemia, hemorrhage, and edema were common after the SCJ injection procedure and conjunctival hemorrhage was common after the IVT injection procedure. Three patients experienced ocular adverse events considered possibly related to study drug: Conjunctival edema and reduced visual acuity were reported in 1 SCJ patient each and iritis was reported in 1 IVT patient. No serious ocular adverse events were reported. No nonocular adverse events were considered related to study drug. Systemic exposure to sirolimus was low, with blood concentrations below levels necessary for systemic immunosuppression. For the SCJ group (n = 25), a median increase in BCVA started at day 7 (5.0 letters) and was 3.0, 4.0, and 4.0 letters at days 14, 45 and 90, respectively. At day 45, median decrease in retinal thickness was -23.7 μm. For the IVT group (n = 25), the median increase in BCVA was 2.0 letters at day 7; at days 14, 45, and 90, the median increase was maintained (4.0 letters); the median decrease in retinal thickness was -52.0 μm at day 45.. Locally administered sirolimus was well-tolerated with minimal systemic exposure at all doses tested in this small phase I population. These findings support advancing the present sirolimus formulation into phase II studies.. Proprietary or commercial disclosure may be found after the references.

Topics: Conjunctiva; Diabetic Retinopathy; Female; Humans; Immunosuppressive Agents; Intravitreal Injections; Macular Edema; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

To expand the paucity of data on the efficacy of various drug-eluting stents in diabetic patients.. Type 2 diabetic patients treated in our institution from October 2005 to January 2007 presenting with of de novo lesions in native coronary arteries were randomly assigned to sirolimus-eluting stents (Cypher group; n=76); paclitaxel-eluting stents (Taxus group; n=75); and everolimus-eluting stents (Endeavor group; n=75). Poor metabolic control (HbA1c >7% and low-density lipoprotein cholesterol >100 mg/dL) and microvascular complications (retinopathy and/or nephropathy) were assessed. The primary end point was the 3-year composite of major adverse cardiac events (MACE), including death of any cause, myocardial infarction, and clinically driven target vessel revascularization. MACE-free survival was 86.8% in the Cypher group, 82.5% in the Taxus group, and 64.4% in the Endeavor group (P=0.006 by log-rank test). The post hoc comparisons showed no significant difference between Cypher versus Taxus groups (adjusted P=1.0) but a higher MACE rate in the Endeavor group versus both the Cypher group (adjusted P=0.012) and the Taxus group (adjusted P=0.075). Independent predictors of 3-year MACE at Cox analysis were treatment by Endeavor versus Cypher stent (2.35 [95% confidence interval, 1.07 to 5.41]; P=0.030), multivessel disease (hazard ratio, 1.78 [95% confidence interval, 1.06 to 2.66]; P=0.031), diabetic retinopathy (hazard ratio, 1.60; [95% confidence interval, 1.03 to 2.76]; P=0.038), and poor metabolic control (hazard ratio, 1.60; [95% confidence interval, 1.02 to 2.52]; P=0.048).. The present pilot study suggests that in diabetic patients, the Endeavor stent is associated with a higher 3-year MACE rate when compared with Cypher and Taxus stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Pilot Projects; Sirolimus

Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data.. In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes.. Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar.. Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.

Topics: Aged; Blood Glucose; Conjunctiva; Diabetic Retinopathy; Female; Fluorescein Angiography; Glycated Hemoglobin; Humans; Immunosuppressive Agents; Injections, Intraocular; Macular Edema; Male; Middle Aged; Pilot Projects; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Visual Acuity

Diabetic retinopathy (DR) is a potentially blinding complication resulting from diabetes mellitus (DM). Retinal vascular endothelial cells (RMECs) dysfunction occupies an important position in the pathogenesis of DR, and mitochondrial disorders play a vital role in RMECs dysfunction. However, the detailed mechanisms underlying DR-induced mitochondrial disorders in RMECs remain elusive. In the present study, we used High glucose (HG)-induced RMECs in vitro and streptozotocin (STZ)-induced Sprague-Dawley rats in vivo to explore the related mechanisms. We found that HG-induced mitochondrial dysfunction via mitochondrial Dynamin-related protein 1(Drp1)-mediated mitochondrial fission. Drp1 inhibitor, Mdivi-1, rescued HG-induced mitochondrial dysfunction. Protein Kinase Cδ (PKCδ) could induce phosphorylation of Drp1, and we found that HG induced phosphorylation of PKCδ. PKCδ inhibitor (Go 6983) or PKCδ siRNA reversed HG-induced phosphorylation of Drp1 and further mitochondrial dysfunction. The above studies indicated that HG increases mitochondrial fission via promoting PKCδ/Drp1 signaling. Drp1 induces excessive mitochondrial fission and produces damaged mitochondrial, and mitophagy plays a key role in clearing damaged mitochondrial. Our study showed that HG suppressed mitophagy via inhibiting LC3B-II formation and p62 degradation. 3-MA (autophagy inhibitor) aggravated HG-induced RMECs damage, while rapamycin (autophagy agonist) rescued the above phenomenon. Further studies were identified that HG inhibited mitophagy by down-regulation of the PINK1/Parkin signaling pathway, and PINK1 siRNA aggravated HG-induced RMECs damage. Further in-depth study, we propose that Drp1 promotion of Hexokinase II (HK-II) separation from mitochondria, thus inhibiting HK-II-PINK1-mediated mitophagy. In vivo, we found that intraretinal microvascular abnormalities (IRMA), including retinal vascular leakage, acellular capillaries, and apoptosis were increased in STZ-induced DR rats, which were reversed by pretreatment with Mdivi-1 or Rapamycin. Altogether, our findings provide new insight into the mechanisms underlying the regulation of mitochondrial homeostasis and provide a potential treatment strategy for Diabetic retinopathy.

Topics: Animals; Diabetes Mellitus; Diabetic Retinopathy; Dynamins; Endothelial Cells; Homeostasis; Mitochondria; Protein Kinases; Rats; Rats, Sprague-Dawley; RNA, Small Interfering; Sirolimus

Microvascular changes are the earliest adverse events in diabetic retinopathy, but recent studies have shown that oxidative stress induced by photoreceptors is associated with the development of the retinopathy. The purpose of this study was to determine the roles played by superoxides formed by photoreceptors under hyperglycemic conditions on autophagy. To accomplish this, we cultured 661 W cells, a transformed murine cone cell line, with 5.5 or 25 mM glucose in the presence or absence of 3 methyl adenine (3MA) or rapamycin. The superoxides were determined by flow cytometry using hydroethidine as a fluorescence probe. The autophagy activity was determined by changes in the expression of LC3B2 and P62 by immunoblotting. The degree of mitophagy was determined by the accumulation of mitochondria and lysosomes. Apoptotic changes of 661 W cells were determined by the caspase 3/7 activities. Our results showed higher levels of P62 and superoxides in cells cultured in 25 mM glucose than in 5.5 mM glucose. Addition of 3MA caused a significant increase of P62, superoxides, and caspase 3/7 activities in the 661 W cells cultured in high glucose but not in low glucose. These findings suggest that autophagy is important for the functioning and survival of 661 W cells under hyperglycemic conditions.

Topics: Adenine; Animals; Autophagy; Cell Line; Cell Survival; Diabetic Retinopathy; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucose; Mice; Microtubule-Associated Proteins; Models, Biological; Oxidative Stress; Retinal Cone Photoreceptor Cells; Sequestosome-1 Protein; Sirolimus; Superoxides

Diabetic retinopathy (DR) is a retinal disease caused by metabolic disorders of glucose tolerance that can lead to irreversible blindness if not adequately treated. Retinal pigment epithelial cell (RPEC) dysfunction contributes to the pathogenesis of DR. In the present study the anti‑inflammatory effect of curcumin (CUR) was investigated in RPECs damaged by high glucose levels. RPEC treated with 30 mmol/l glucose was regarded as high glucose group, and cells treated with 24.4 mmol/l mannitol was set as equivalent osmolarity group. Cell Counting Kit‑8 assay was used to measure RPEC viability, the expression of phosphorylated (p)‑AKT and p‑mammalian target of rapamycin (mTOR) were assessed by western blot, and secretion of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β in the culture medium was measured by ELISA. Intracellular reactive oxygen species (ROS) levels were measured by laser scanning confocal microscope. The present data indicated that, compared with mannitol treatment, high glucose treatment reduced RPEC viability, increased TNF‑α, IL‑6 and IL‑1β secretion, increased ROS formation and promoted phosphorylation of AKT and mTOR. The antioxidant N‑acetylcysteine, the phosphoinositide 3‑kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. In addition, pretreatment with 10 µmol/l CUR reduced secretion levels of TNF‑α, IL‑6 and IL‑1β, ROS formation and phosphorylation of AKT and mTOR. In conclusion, CUR inhibited high glucose‑induced inflammatory injury in RPECs by interfering with the ROS/PI3K/AKT/mTOR signaling pathway. The present study may reveal the molecular mechanism of CUR inhibition effects to high glucose‑induced inflammatory injury in RPEC.

Topics: Acetylcysteine; Anti-Inflammatory Agents; Antioxidants; Cell Line; Chromones; Curcumin; Diabetic Retinopathy; Drug Synergism; Epithelial Cells; Gene Expression Regulation; Glucose; Humans; Interleukin-1beta; Interleukin-6; Models, Biological; Morpholines; Oxidative Stress; Phosphatidylinositol 3-Kinase; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Retinal Pigment Epithelium; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

Cones are the primary photoreceptor (PR) cells responsible for vision in humans. They are metabolically highly active requiring phosphoinositide 3-kinase (PI3K) activity for long-term survival. One of the downstream targets of PI3K is the kinase mammalian target of rapamycin (mTOR), which is a key regulator of cell metabolism and growth, integrating nutrient availability and growth factor signals. Both PI3K and mTOR are part of the insulin/mTOR signaling pathway, however if mTOR is required for long-term PR survival remains unknown. This is of particular interest since deregulation of this pathway in diabetes results in reduced PR function before the onset of any clinical signs of diabetic retinopathy. mTOR is found in two distinct complexes (mTORC1 & mTORC2) that are characterized by their unique accessory proteins RAPTOR and RICTOR respectively. mTORC1 regulates mainly cell metabolism in response to nutrient availability and growth factor signals, while mTORC2 regulates pro-survival mechanisms in response to growth factors. Here we analyze the effect on cones of loss of mTORC1, mTORC2 and simultaneous loss of mTORC1 & mTORC2. Interestingly, neither loss of mTORC1 nor mTORC2 affects cone function or survival at one year of age. However, outer and inner segment morphology is affected upon loss of either complex. In contrast, concurrent loss of mTORC1 and mTORC2 leads to a reduction in cone function without affecting cone viability. The data indicates that PI3K mediated pro-survival signals diverge upstream of both mTOR complexes in cones, suggesting that they are independent of mTOR activity. Furthermore, the data may help explain why PR function is reduced in diabetes, which can lead to deregulation of both mTOR complexes simultaneously. Finally, although mTOR is a key regulator of cell metabolism, and PRs are metabolically highly active, the data suggests that the role of mTOR in regulating the metabolic transcriptome in healthy cones is minimal.

Topics: Animals; Cell Survival; Diabetic Retinopathy; Disease Models, Animal; Electroretinography; Eye Proteins; Immunosuppressive Agents; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Mice; Mice, Inbred C57BL; Multiprotein Complexes; Phosphatidylinositol 3-Kinases; Retinal Cone Photoreceptor Cells; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

To evaluate the role of rapamycin in the prevention of diabetic oxidative stress and the regulation of angiogenic factors.. Experimental animal study.. Diabetes was induced in 20 adult male Wistar rats by a single intraperitoneal administration of streptozotocin (60 mg/kg). Rats were randomly assigned into diabetic and rapamycin groups (n = 10). Ten healthy normal adult male rats of same age formed the control group. All groups were followed for 3 months. Rapamycin group received 1 mg/kg rapamycin via orogastric gavage during the last 4 weeks. At the end of 12 weeks, rats were sacrificed and biochemical oxidative stress markers (malondialdehyde and nitrotyrosine), together with vascular endothelial growth factor, hypoxia-inducible factor-1α, and pigment epithelium-derived factor, were measured in the retina. Blood biochemical analyses were also done.. In the diabetic group, retinal malondialdehyde and nitrotyrosine levels were increased in comparison with control and rapamycin groups (p < 0.05). Rapamycin suppressed oxidative stress and showed a beneficial effect. It also decreased all angiomodulator cytokines compared with the diabetic group (p < 0.05). Correspondingly, rapamycin also decreased plasma malondialdehyde levels compared with the diabetic group (p = 0.037).. Rapamycin may have a protective role against diabetes-induced oxidative retinal injury and may decrease angiomodulator cytokines.

Topics: Angiogenesis Modulating Agents; Animals; Anti-Bacterial Agents; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Eye Proteins; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Malondialdehyde; Nerve Growth Factors; Oxidative Stress; Rats; Rats, Wistar; Serpins; Sirolimus; Tyrosine; Vascular Endothelial Growth Factor A

The effects of the antiangiogenic cytokine PEDF on key steps in retinal angiogenesis, specifically endothelial cell proliferation and vascular tubule formation, and the regulation of PEDF expression in retinal capillary endothelial cells were evaluated. HUVECs were co-cultured with fibroblasts to construct a model of angiogenesis using the Angiokit assay, and image analysis software was used to measure the effects of PEDF and VEGF on vascular tubule formation. Quantitative real-time PCR analysis was used to determine the expression of PEDF in microvascular endothelial cells exposed to glucose 20 mM, insulin 100 nM and VEGF 10 ng/ml. PEDF inhibited endothelial cell proliferation and significantly decreased the number of tubules (629+93 AU vs 311+31, p=0.001), number of branching points (145+19 AU vs 46+5, p=0.03) and total tubule length (4848+748 AU vs 11,172+2353, p=0.001). In bovine retinal capillary endothelial cells (BRCECs), PEDF mRNA and protein expression was suppressed by insulin (22%) in a rapamycin-sensitive manner; wortmannin had no effect. PEDF mRNA expression was also significantly reduced in the presence of high glucose (23%) and VEGF (25%). In conclusion, PEDF inhibits key steps in the angiogenic response of BRCECs, including endothelial cell proliferation and vascular tubule formation. Gene expression of PEDF is negatively regulated by glucose, insulin (via an mTOR-dependent pathway) and VEGF.

Topics: Androstadienes; Angiostatic Proteins; Animals; Cattle; Cell Proliferation; Cells, Cultured; Diabetic Retinopathy; Endothelial Cells; Enzyme Inhibitors; Eye Proteins; Gene Expression; Gene Expression Regulation; Glucose; Humans; Insulin; Neovascularization, Physiologic; Nerve Growth Factors; Retinal Vessels; Serpins; Sirolimus; Umbilical Cord; Vascular Endothelial Growth Factor A; Wortmannin

Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) represent the most common causes of vision loss in patients affected by diabetes mellitus. Diabetic retinopathy (DR) needs special attention because of its high public health impact and impact on quality of life of patients. Actually, laser retinal photocoagulation is the standard of care for the treatment of DR. However, laser treatment reduces the risk of moderate visual loss by approximately 50%, without a remarkable vision recovery. Thus, new approaches in the treatment of DR have been taken into account and, more specifically, the therapy employing antivascular endothelial growth factor (anti-VEGF) drugs could play a meaningful role. VEGF is a pluripotent growth factor that functions as an endothelial cell-specific mitogen and vasopermeability factor. Through these mechanisms VEGF plays a critical role in promoting angiogenesis and vascular leakage. A high level of VEGF has been detected in eyes presenting DME and PDR, and thereby VEGF is an attractive candidate as therapeutic target of pharmacological treatment in the management of DR. In the current chapter, the concepts and results of anti-VEGF therapy in the treatment of the DME and PDR are presented.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Bevacizumab; Diabetic Retinopathy; Humans; Macular Edema; Ranibizumab; RNA, Small Interfering; Sirolimus; Vascular Endothelial Growth Factor A

Topics: Carcinoma, Squamous Cell; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Everolimus; Humans; Liver Transplantation; Male; Middle Aged; Proteinuria; Sirolimus

Patients with diabetic retinopathy (DR) have an increased risk of death from coronary heart disease and myocardial infarction. The purpose of this study was to compare the outcomes of revascularization strategies (sirolimus-eluting stent [SES] and coronary artery bypass surgery [CABG]) in patients with DR according to the stage of retinopathy: non-proliferative retinopathy (NPDR) and proliferative retinopathy (PDR).. From April 2004 until February 2007, 627 patients including 51 NPDR and 62 PDR patients underwent SES implantation. For each retinopathy group, a historical comparison group at the same stages of retinopathy undergoing CABG was selected. Cardiac events were defined as a composite of cardiac death, myocardial infarction, and repeat revascularization.. The average follow-up from the time of the initial revascularization was 27.7 ± 8.5 months for NPDR-SES patients, 69.6 ± 36.6 months for NPDR-CABG patients, 26.4 ± 9.7 months for PDR-SES patients, and 68.3 ± 44.2 months for PDR-CABG patients; and Kaplan-Meier estimates of the percentages of events at 24 months were 47.0%, 22.8%, 28.5%, and 26.0%. Kaplan-Meier curves for cardiac events differed significantly between the SES group and the CABG group in NPDR patients (p = 0.04), whereas the curves did not differ significantly between the two groups of PDR patients. The adjusted hazard ratio of SES implantation for cardiac events in the entire group of DR patients was 1.75 (95% confidence interval [CI] 1.02-3.00, p = 0.04).. SES implantation is not a suitable method of revascularization in DR patients, especially in NPDR patients. CABG may become the first-choice revascularization technique for these patients.

Topics: Aged; Coronary Artery Bypass; Coronary Disease; Diabetic Retinopathy; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Sirolimus; Treatment Outcome

The prognostic value of identifying the retinal status of diabetic patients undergoing coronary implantation of drug-eluting stents is unknown.. We evaluated the outcomes of 318 consecutive patients undergoing implantation of sirolimus-eluting stents for coronary artery disease. Patients were divided into 5 groups according to the diabetic and retinal status: diabetic patients without retinopathy (43 patients); diabetic patients with nonproliferative retinopathy (34); diabetic patients with proliferative retinopathy (37); diabetic patients with unknown retinal status (30); and nondiabetic patients (174).. During a mean follow-up of 385 days, 64 patients had target-vessel failure (defined as a composite of death from cardiac causes, myocardial infarction, and target-vessel revascularization). At 1 year, Kaplan-Meier estimates of the rate of target-vessel failure were 15.3% for diabetic patients without retinopathy, 56.6% for those with nonproliferative retinopathy, 17.3% for those with proliferative retinopathy, 19.0% for those with unknown retinal status, and 16.0% for nondiabetic patients. After adjustment for the potential confounders and differences between groups, the relation of nonproliferative retinopathy to target-vessel failure remained significant. In an analysis in which diabetic patients without retinopathy were used as the reference group, the hazard ratios for target-vessel failure were 3.9 for those with nonproliferative retinopathy, 1.3 for those with proliferative retinopathy, 1.1 for those with unknown retinal status, and 1.4 for nondiabetic patients (P for trend = 0.015).. As compared with diabetic patients without retinopathy, those with nonproliferative retinopathy have an increased risk for target-vessel failure after coronary implantation of sirolimus-eluting stents.

Topics: Aged; Case-Control Studies; Coronary Artery Disease; Diabetic Retinopathy; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Prospective Studies; Risk; Sirolimus; Stents; Treatment Failure; Treatment Outcome

We compared the 1-year outcome of coronary revascularization with sirolimus-eluting stents (SESs) or coronary artery bypass grafting (CABG) for coronary artery disease involving the left anterior descending artery (LAD) in diabetic patients according to their retinal status: no diabetic retinopathy (NDR) and diabetic retinopathy (DR).. Between April 2004 and October 2005, 220 consecutive patients with coronary artery disease involving the LAD underwent implantation of SESs; of these, 25 patients had NDR and 54 had DR. For each group, we included a comparison group of diabetic patients who had undergone CABG and had the same retinal status.. During 1 year after revascularization, five cardiac events (cardiac death, myocardial infarction, and repeat revascularization) were noted in NDR-SES patients, four in NDR-CABG, 24 in DR-SES, and eight in DR-CABG patients. Most cardiac events were repeat revascularizations. Kaplan-Meier estimates of the incidence of cardiac events at 1 year were 21.1%, 11.4%, 44.0%, and 14.0%, respectively. Kaplan-Meier curves for cardiac events in SES patients were different from those of CABG patients for the DR group (p = 0.003), but not NDR groups. After adjustments for the potential confounders, the hazard ratio of cardiac events in DR-SES patients was 2.8 (95% confidence interval, 1.1 to 6.9; p = 0.02).. Compared with SES implantation, CABG is more suitable for revascularization in patients with coronary artery disease involving the LAD and DR.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Disease; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Retrospective Studies; Sirolimus; Stents