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: 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

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 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: 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

OBJECTIVETo observe the prevention and clinical efficacy of combination of Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic retinopathy (DR).

METHODSUsing randomized, double-blind, double simulation, parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM) outpatients were recruited and assigned to the treatment group and the control group, 70 in each group. All patients received basic Western medicine treatment (such as blood glucose and pressure control). Patients in the treatment group took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times per day), while those in the control group took LDP placebos and GLT placebos. All treatment lasted for 24 consecutive months. All subjects were followed-up every month. The general clinical data as sex, age, and metabolic data such as blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected and statistically analyzed.

RESULTSThere was no significant difference in levels of blood glucose, blood pressure, or blood lipid between the two groups (P > 0.05). After treatment the DR incidence rate was significantly lower in the treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P < 0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59), P < 0.05].

CONCLUSIONCombination of LDP and GLT could effectively prevent and treat the development of DR in T2DM patients.

Blood Glucose ; analysis ; Blood Pressure ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Humans ; Phytotherapy ; Tablets

PURPOSE: This study was designed to compare the change of renal function before and after fluorescein angiography in patients with diabetic retinopathy. METHODS: This study included 80 patients diagnosed with diabetic retinopathy who did not receive dialysis from April 2004 to December 2014. Based on retrospective analysis of a blood test performed within one week before and after fluorescein angiography, the changes of blood urea nitrogen (BUN), serum creatinine (Scr), and estimated glomerular filtration rate (eGFR) were measured. Additionally, the effect of fluorescein angiography on renal function was estimated according to chronic kidney disease (CKD) stage. RESULTS: The average BUN/SCr before and after fluorescein angiography was not statistically significantly different before and after fluorescein angiography. The average eGFR before and after fluorescein angiography increased from 62.62 ± 31.59 to 66.46 ± 31.22 (p = 0.006). Regarding changes in renal functions according to CKD stage, based on the average eGFR in CKD stages 5, 4, 2, and 1, no significant differences were observed in renal functions before and after fluorescein angiography, whereas eGFR was significantly increased after fluorescein angiography at CKD stage 3 (p = 0.042). CONCLUSIONS: In patients with diabetic retinopathy, BUN/Scr and eGFR were not significantly different before or after fluorescein angiography. Moreover, the deterioration of renal function was not observed at any CKD stage. Therefore, fluorescein angiography is a relatively safe diagnostic examination in patients with diabetic retinopathy who did not receive dialysis due to the low-risk of renal function deterioration.
Blood Urea Nitrogen ; Creatinine ; Diabetic Retinopathy* ; Dialysis ; Fluorescein Angiography* ; Fluorescein* ; Glomerular Filtration Rate ; Hematologic Tests ; Humans ; Renal Insufficiency, Chronic ; Retrospective Studies