Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.
Blood-Retinal Barrier ; Diabetic Retinopathy ; Humans ; Macular Degeneration ; Phenotype ; Retinal Diseases

Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using state-of-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.
Animals ; Brain ; blood supply ; physiology ; physiopathology ; Brain Diseases ; physiopathology ; Capillaries ; physiology ; Cellular Microenvironment ; Diabetic Retinopathy ; physiopathology ; Endothelial Cells ; physiology ; Humans ; Pericytes ; physiology ; Vascular Remodeling

BACKGROUND: Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment. METHODS: A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L). RESULTS: The proportion of patients with diabetic retinopathy (DR) (P for trend < 0.001), coronary heart disease (CHD) (P for trend < 0.001), and stroke (P for trend < 0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables. CONCLUSION: Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.
Blood Glucose ; Confounding Factors (Epidemiology) ; Coronary Disease ; Cystatin C* ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy ; Humans ; Retrospective Studies ; Risk Factors ; Stroke

PURPOSE: We investigated systemic risk factors for clinically significant macula edema (CSME) within 1 year after pan-retinal photocoagulation in patients with proliferative diabetic retinopathy. METHODS: A retrospective chart review was performed on 171 patients who received pan-retinal photocoagulation at our hospital from January 2010 to December 2016. The patients were divided into Group Ⅰ with CSME (85 eyes) and Group II without CSME (86 eyes). The associations between presence of CSME and glycated hemoglobin (HbA1c), duration of diabetes, systolic and diastolic blood pressure (BP), body mass index (BMI), lipid status, sex, and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: In the present study of 171 patients, there was no significant difference in age and gender distribution between the two groups. Duration of diabetes, total serum cholesterol, serum low density lipoprotein, HbA1c, and eGFR were significantly higher in patients with CSME (p < 0.05). Serum high-density lipoprotein, triglycerides, BMI, and systolic and diastolic BP showed no correlation with CSME. Multiple logistic regression analysis showed that total serum cholesterol and HbA1c values had significantly high odds of developing CSME. CONCLUSIONS: HbA1c, total serum cholesterol, and eGFR are important risk factors associated with CSME in patients with proliferative diabetic retinopathy secondary to pan-retinal photocoagulation. Thus, early detection of these risk factors and their control have significant roles in preventing the development and progression of maculopathy and thereby preventing severe visual loss.
Blood Pressure ; Body Mass Index ; Cholesterol ; Diabetic Retinopathy* ; Edema ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated ; Humans ; Light Coagulation ; Lipoproteins ; Logistic Models ; Retrospective Studies ; Risk Factors ; Triglycerides

PURPOSE: To evaluate the factors that are significant in progression to neovascular glaucoma in patients with proliferative diabetic retinopathy. METHODS: In this retrospective analysis, we reviewed the medical records of 52 patients who were first diagnosed with proliferative diabetic retinopathy from March 2014 to March 2016. We compared diabetes mellitus period, HbA1c, chronic diseases such as hypertension, hyperlipidemia, and kidney disease, insulin treatments, blood urea nitrogen, blood creatinine, glomerular filtration rate, urine albumin, dialysis, corrected visual acuity at the first visit, traction membrane sign of the retina at the first visit, vitreous hemorrhage and preretinal hemorrhage in each group and then investigated the prognostic factors of neovascular glaucoma. RESULTS: A total of 52 patients were included in the investigation, 12 patients (23.08%) were diagnosed with iris neovascularization and 4 patients (7.69%) developed neovascular glaucoma. The patients without iris neovascularization were defined as Group I, those with iris neovascularization as Group II, and those with neovascular glaucoma as Group III. The diabetes mellitus period was significantly longer in Group II (10.88 ± 7.14 years) and in Group III (11.75 ± 8.61 years) than Group I (8.30 ± 5.25 years) (p-value 0.41, 0.032, respectively). The HbA1c level was 9.59 ± 2.23 in Group II and 9.27 ± 2.54 in Group I. There was no significant difference between the two groups (p = 0.721). However, HbA1c was significantly higher in Group III (11.55 ± 0.21) than Group I (p-value 0.048). CONCLUSIONS: A long diabetes mellitus period and high HbA1c level have a significant effect on the progression to neovascular glaucoma in patients with proliferative diabetic retinopathy. This information could be useful for predicting and preventing the prognosis of patients.
Blood Urea Nitrogen ; Chronic Disease ; Creatinine ; Diabetes Mellitus ; Diabetic Retinopathy* ; Dialysis ; Glaucoma, Neovascular* ; Glomerular Filtration Rate ; Hemorrhage ; Humans ; Hyperlipidemias ; Hypertension ; Insulin ; Iris ; Kidney Diseases ; Medical Records ; Membranes ; Prognosis ; Retina ; Retrospective Studies ; Traction ; Visual Acuity ; Vitreous Hemorrhage

PURPOSE: To compare retinal layer thickness in non-proliferative diabetic retinopathy in type 2 diabetic patients as measured by optical coherence tomography. METHODS: A total of 108 eyes from 71 patients, between January 2015 and July 2016, were included in this study. Of these, 39 eyes were included in the control group, 38 eyes in the diabetic group without non-proliferative diabetic retinopathy, and 31 eyes in the non-proliferative diabetic retinopathy group (NPDR). We measured the thickness of each retinal layer by optical coherence tomography (OCT). A total of ten layers were evaluated including the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), inner retinal layer (IRL), outer retinal layer (ORL), and the total retinal layer (TRL). We compared the superior, inferior, nasal, and temporal regions at 1–3mm from the central fovea. RESULTS: RNFL was thinner in the superior region of the NPDR, as compared with that of the control group, showing statistical significance (p = 0.016). The thickness of all regions in the GCL, IPL, and IRL were decreased in NPDR, as compared to the control group with statistical significance. In addition, the thickness of the superior region in the GCL, IPL, and IRL showed statistically significant differences between controls and the no diabetic retinopathy (DR) group (p = 0.026, 0.003, 0.003). The thickness of the INL, OPL plus ONL, RPE, and ORL in all three groups showed no significant difference. The differences in the decreased thickness in the IRL were similar to that of TRL. CONCLUSIONS: Retinal neurodegeneration was observed in the IRL, which included changes to the RNFL, GCL, and IPL in early type 2 diabetes before microvascular injury was apparent. Thorough control of blood glucose is required in early diabetes, and further studies to delay retinal neurodegeneration are required. OCT might have an important role in early diagnosis and follow up of diabetic retinopathy.
Blood Glucose ; Diabetic Retinopathy* ; Early Diagnosis ; Follow-Up Studies ; Ganglion Cysts ; Humans ; Nerve Fibers ; Retinal Pigment Epithelium ; Retinaldehyde* ; Temporal Lobe ; Tomography, Optical Coherence

PURPOSE: To investigate the effect of cilostazol on ocular hemodynamics and to determine whether the administration of cilostazol increases the ocular blood flow in patients with diabetic retinopathy. METHODS: This prospective observational study investigated the effect of orally administered cilostazol on diabetic retinopathy. Before and after administration for 1 week, pulsatile ocular blood flow (POBF) and retrobulbar hemodynamics were measured using a POBF analyzer and transcranial Doppler imaging, respectively. Visual acuity, intraocular pressure, and blood pressure were also evaluated before and after treatment. RESULTS: Twenty-five eyes of 25 patients were included in this study. POBF increased significantly (16.8 ± 4.6 µL/sec vs. 19.6 ± 6.2 µL/sec, p < 0.001) after administration of cilostazol, while no significant change was identified in visual acuity, intraocular pressure, and blood pressure. Mean flow velocity in the ophthalmic artery as measured with transcranial Doppler imaging also increased significantly after medication (23.5 ± 5.6 cm/sec vs. 26.0 ± 6.9 cm/sec, p = 0.001). The change in POBF directly correlated with the change in mean flow velocity (r = 0.419, p = 0.007). CONCLUSIONS: Cilostazol was effective in increasing ocular blood flow in patients with diabetic retinopathy, possibly by modulating retrobulbar circulation.
Administration, Oral* ; Blood Flow Velocity ; Blood Pressure ; Diabetic Retinopathy* ; Hemodynamics ; Humans ; Intraocular Pressure ; Observational Study ; Ophthalmic Artery ; Prospective Studies ; Pulsatile Flow ; Visual Acuity

PURPOSE: To investigate the systemic parameters related to changes in the retinal microvasculature using optical coherence tomography angiography (OCTA) in diabetic patients without diabetic retinopathy. METHODS: We retrospectively reviewed the medical records of diabetic patients without diabetic retinopathy. All patients showed normal fundus on dilated fundus examinations. OCTA (DRI OCT Triton, Topcon Corporation, Tokyo, Japan) was performed on a 3 × 3 mm area centered at the fovea. The foveal avascular zone (FAZ) area and vascular density (VD) of the superficial and deep capillary plexus (SCP/DCP) were measured. Multiple regression analysis was conducted to evaluate the relationship between microvascular indexes on OCTA and systemic parameters including sex, age, duration of diabetes mellitus (DM), hemoglobin A1c (HbA1c), total cholesterol, presence of hypertension (HTN) and systolic and diastolic blood pressure (SBP/DBP). RESULTS: A total of 35 eyes of 35 patients were included in this study. The mean age was 55.7 ± 11.6 years, the mean duration of DM was 52.4 ± 88.7 months and the mean HbA1c was 8.8 ± 2.3%. The FAZ area of the DCP increased significantly as the HbA1c level increased (p < 0.001), but the other parameters, i.e., sex, age, duration of DM, total cholesterol, presence of HTN, SBP and DBP, did not exhibit significant relations in the DCP (p = 0.727, 0.280, 0.385, 0.816, 0.206, 0.055 and 0.092, respectively). There were no significant relationships between systemic parameters and the FAZ area in the SCP (p > 0.05). No systemic parameters exhibited significant relationships with VD in either the SCP or the DCP (p > 0.05). CONCLUSIONS: The FAZ area of the DCP detected via OCTA increased as the level of HbA1c increased, although the patients did not show diabetic retinopathy on dilated fundus examinations. Therefore, clinicians should consider this when screening diabetic patients for diabetic retinopathy.
Angiography ; Blood Pressure ; Capillaries ; Cholesterol ; Diabetes Mellitus ; Diabetic Retinopathy* ; Humans ; Hypertension ; Mass Screening ; Medical Records ; Microvessels* ; Neptune ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence

BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR. METHODS: We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m²): no DKD (uACR <30 and eGFR ≥60), non-severe DKD (uACR ≥30 or eGFR <60), and severe DKD (uACR ≥30 and eGFR <60). Mean systolic and diastolic blood pressure, mean glycosylated hemoglobin (HbA1c) level, and HbA1c variability (standard deviation [SD] of serial HbA1c values or HbA1c-SD) were calculated for the preceding 2 years. RESULTS: The prevalence of no DKD, non-severe DKD, and severe DKD was 37.2% (n=118), 37.0% (n=117), and 25.8% (n=82), respectively. HbA1c-SD and the triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD. CONCLUSION: The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients.
Blood Pressure ; Cholesterol ; Cholesterol, HDL ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2* ; Diabetic Nephropathies* ; Diabetic Retinopathy* ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated ; Humans ; Linear Models ; Lipoproteins ; Logistic Models ; Phenotype ; Prevalence ; Risk Factors* ; Triglycerides

PURPOSE: To evaluate the prevalence of anterior type diabetic retinopathy (DR) using ultra-widefield fluorescein angiography and to identify the factors associated with anterior type DR incidence. METHODS: A retrospective case review was used in this study. Patients with non-proliferative diabetic retinopathy (NPDR) underwent examination by ultra-widefield fluorescein angiography, and were classified into anterior, posterior, or diffuse DR groups. Anterior DR was defined if diabetic retinal changes were noted only at the location anterior to the imaginary circle bordered by the Early Treatment Diabetic Retinopathy Study seven-standard fields. Correlations between demographic data, as well as systemic and ocular factors, and the incidence of NPDR types were evaluated. RESULTS: Among the 234 eyes of 234 patients with NPDR, 25 eyes (10.7%) demonstrated anterior DR. Anterior DR was observed in 10 eyes (30.3%) of patients having mild NPDR, three eyes (4.8%) of moderate NPDR patients, and in 12 eyes (7.1%) of severe NPDR patients (p < 0.001). The incidence of anterior DR positively correlated with lower hemoglobin A1c levels and with greater high-density lipoprotein levels following multiple logistic regression analysis (p < 0.001). The mean hemoglobin A1c level was 7.03 ± 0.99% in anterior DR, 7.99 ± 1.74% in posterior DR, and 7.94 ± 1.39% in diffuse DR patients (p = 0.003). The mean high-density lipoprotein level was 51.2 ± 12.5 mg/dL in anterior, 49.7 ± 15.2 mg/dL in posterior, and 45.2 ± 13.1 mg/dL in diffuse DR patients (p = 0.010). CONCLUSIONS: Diabetic retinal changes confined to an anterior location were more frequently noted in earlier stages of NPDR. The incidence of DR sparing posterior retinal involvement was related to favorable blood sugar and lipid profiles.
Angiography* ; Blood Glucose ; Diabetic Retinopathy* ; Fluorescein Angiography ; Humans ; Incidence ; Lipoproteins ; Logistic Models ; Prevalence ; Retinaldehyde ; Retrospective Studies