Pseudo-Wet Plasma Mechanism Enabling High-Throughput Dry Etching of SiO2 by Cryogenic-Assisted Surface Reactions.

Manufacturing semiconductor devices requires advanced patterning technologies, including reactive ion etching (RIE) based on the synergistic interactions between ions and etch gas. However, these interactions weaken as devices continuously scale down to sub-nanoscale, primarily attributed to the diminished transport of radicals and ions into the small features. This leads to a significant decrease in etch rate (ER). Here, a novel synergistic interaction involving ions, surface-adsorbed chemistries, and materials at cryogenic temperatures is found to exhibit a significant increase in the ER of SiO2 using CF4/H2 plasmas. The ER increases twofold when plasma with H2/(CF4 + H2) = 33% is used and the substrate temperature is lowered from 20 to -60 °C. The adsorption of HF and H2O on the SiO2 surface at cryogenic temperatures is confirmed using in situ Fourier transform infrared spectroscopy. The synergistic interactions of the surface-adsorbed HF/H2O as etching catalysts and plasma species result in the ER enhancement. Therefore, a mechanism called "pseudo-wet plasma etching" is proposed to explain the cryogenic etching process. This synergy demonstrates that the enhanced etch process is determined by the surface interactions between ions, surface-adsorbed chemistry, and the material being etched, rather than interactions between ion and gas phase, as observed in the conventional RIE.

Involvements of choroidal vascular structures with local treatments in patients with diabetic macular edema.

PURPOSE: To examine changes of the choroidal morphology in patients with diabetic macular edema (DME) before and after local treatments. METHODS: This study was on 20 eyes with DME, observed for more than 24 months. All patients underwent laser photocoagulation (Laser), sub-tenon triamcinolone acetonide injection (TA), or intravitreal aflibercept injection (IVA). Central macular and choroidal thicknesses (CMT/CCT), and choroidal vascular structures consisting of the total choroidal area (TCA), luminal area (LA), and stromal area (SA) were measured by a binarization method. The ratios of LA in TCA were eventually determined as the L/C ratio in each case. RESULTS: The L/C ratio significantly decreased for 24 months in patients with DME (p = 0.01), whereas no significant differences were noted in other parameters including TCA, LA, SA, or CCT. Among patients treated with Laser ± TA ± IVA, a significant correlation was found between a high L/C ratio at pretreatment and a lower cumulative number of injections (1-2 times/24 months) (p = 0.04). The L/C ratio in pretreatment showed a significantly inverse correlation with CMT (-0.60, p = 0.02) and subsequent BCVA (logMAR) (-0.59, p = 0.03). CONCLUSION: This study highlighted that the L/C ratio in pretreatment might predict a change of the visual acuity in DME.

Choroidal vascular structures in diabetic patients: a meta-analysis.

PURPOSE: Choroidal vascular structures are likely to be affected in diabetic patients. The aim of this study was to conduct a meta-analysis of choroidal vascular structures in diabetic eyes with no diabetic retinopathy (NDR) and healthy control eyes, which was systematically evaluated by various factors involving the measurements. METHODS: This study identified clinical data from publications in PubMed and web of science until May 2020. Independent retrospective or prospective clinical studies comparing NDR and healthy control eyes regarding choroidal vascular structures were extracted. Five related studies were enrolled, cumulating in a total of 282 diabetic eyes and 511 control eyes examined in this study. Heterogeneity was statistically quantified by I2 statistics, and meta-analysis was performed using a random effects model. This study included 2 different algorisms of binarization determining the ratio of luminal areas in total choroidal areas, both of which were consolidated and called "choroidal vascular ratio." RESULTS: Meta-analysis clearly showed that the choroidal vascular ratio was significantly lower in NDR eyes than in healthy control eyes (weighted mean difference = - 2.16; 95%CI: - 3.19 to - 1.13; P < 0.005). Similar results were obtained in sub-analysis based on adjustment of serum HbA1c levels and duration of diabetes. CONCLUSIONS: The choroidal vascular ratio of NDR eyes was significantly lower than that of healthy control eyes. The ratio might contribute to a better understanding of the pathophysiology involved in the development of diabetic retinopathy, although there was some heterogeneity in primary analysis studies.

Etching process of narrow wire and application to tunable-barrier electron pump.

Single electron sources have been studied as a device to establish an electric current standard for 30 years and recently as an on-demand coherent source for fermion quantum optics. In order to construct the single electron source on a GaAs/AlGaAs two-dimensional electron gas (2DEG), it is often necessary to fabricate a sub-micrometer wire by etching. We have established techniques to fabricate the wire made of the fragile 2DEG by combining photolithography and electron beam lithography with one-step photoresist coating, which enables us to etch fine and coarse structures simultaneously. It has been demonstrated that the fabricated single electron source pumps a fixed number of electrons per cycle with radio frequency. The fabrication technique improves the lithography process with lower risk of damage to the 2DEG.

Negative resistance state in superconducting NbSe2 induced by surface acoustic waves.

We report a negative resistance, namely, a voltage drop along the opposite direction of a current flow, in the superconducting gap of NbSe2 thin films under the irradiation of surface acoustic waves (SAWs). The amplitude of the negative resistance becomes larger by increasing the SAW power and decreasing temperature. As one possible scenario, we propose that soliton-antisoliton pairs in the charge density wave of NbSe2 modulated by the SAW serve as a time-dependent capacitance in the superconducting state, leading to the dc negative resistance. The present experimental result would provide a previously unexplored way to examine nonequilibrium manipulation of the superconductivity.

Choroidal Thickness in Diabetic Patients Without Diabetic Retinopathy: A Meta-analysis.

PURPOSE: To evaluate the relationship between diabetic eyes without diabetic retinopathy and healthy eyes in subfoveal choroidal thickness. DESIGN: Systematic review and meta-analysis. METHODS: An independent retrospective or prospective clinical study comparing diabetic eyes without diabetic retinopathy and healthy control eyes in the subfoveal choroidal thickness was selected. This study compiled data from publications in PubMed and Web of Science between January 1, 2008, and November 15, 2019. Heterogeneity was statistically quantified by I2 statistics, and meta-analysis was performed using a random-effects model. RESULTS: Seventeen related studies were identified, including a total of 4,213 eyes, which consisted of 1,197 diabetic eyes without diabetic retinopathy and 3,016 healthy eyes. Meta-analysis clearly showed that the subfoveal choroidal thickness of diabetic eyes without retinopathy was significantly thinner than that of healthy control eyes (weighted mean difference = -14.34 µm; 95% confidence interval: -24.37 to -4.32 µm; P < .005). Similar results were obtained in sub-analysis based on the adjustment of the axial length. CONCLUSIONS: This study suggests that the subfoveal choroidal thickness was thin in diabetic eyes without retinopathy compared to healthy eyes. Subfoveal choroidal thickness might be an important parameter for the development of diabetic retinopathy in diabetic eyes without retinopathy.

Alteration of choroidal vascular structure in diabetic macular edema.

PURPOSE: The aim of this study was to analyze choroidal structures in healthy subjects and patients with/without diabetic macular edema (DME). METHODS: This was a retrospective observation case control study. Four hundred and two eyes of patients with diabetes mellitus (DM), and 124 age-matched eyes of healthy subjects were enrolled in this study. DM patients were divided into 3 groups: presence of central-involved (CI) DME (n = 81) and nonCI-DME/non-DME (n = 321), based on OCT findings. Central choroidal thickness (CCT) and total choroidal, luminal, and stromal areas were determined using EDI-OCT and a binarization method, respectively. The luminal area expressed as a ratio of the total choroidal area was defined as the L/C ratio. RESULTS: DM eyes showed a significantly lower L/C ratio than control eyes, whereas there was no significant difference in CCT or total choroidal, luminal, or stromal areas. There was no significant difference between CI-DME and non-DME groups in HbA1c, blood pressure, dyslipidemia, or renal function. CCT and total choroidal, luminal, and stromal areas were significantly greater in the CI-DME group than non-DME group (each P < 0.05). CONCLUSIONS: These results suggest that CCT was thickened in the presence of DME, associated with both increased luminal and stromal areas, which might be related to the pathology of DME.

Relationship between diabetic macular edema and choroidal layer thickness.

PURPOSE: To investigate the relationship between diabetic macular edema (DME) and the choroidal layer thickness in diabetic patients. METHODS: This is a retrospective observation study. Three hundred eighteen eyes of 159 diabetes mellitus (DM) patients and age-matched 100 eyes of 79 healthy controls were enrolled. DME was defined as over 300 µm in the central retinal subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector. The central choroidal thickness (CCT), as well as inner and outer layers were determined based on enhanced depth imaging (EDI)-OCT. Diabetic patients with/without systemic diabetic treatments (DT) at the start of this study was defined as DT+ and DT-, respectively. The number of eyes examined was 62 and 256 eyes in DME+and DME-groups, respectively. DM patients were further subdivided into 4 groups with/without DME and DT; DME+DT+(35 eyes), DME-DT+(159 eyes), DME+DT-(27 eyes), and DME-DT-group (97 eyes). Multiple comparisons on CCT layers including control and each DM group were statistically examined. RESULTS: The total CCT layer was 254±83, 283±88, and 251±70 µm in the control, DME+, and DME-group, respectively. A total CCT layer in DME+was significantly thicker than the DME-group (P < 0.05). The outer CCT layer was 195±75, 222±83, and 193±63 µm in the control, DME+, and DME-group, respectively. The outer CCT layer in DME+ was significantly thicker than the DME-group (P < 0.05). In the subdivided groups, the total CCT layers in the control, DME+DT+, DME-DT+, DME+DT-and DME-DT-groups were 254±83, 274±88, 247±66, 290±84 and 258±75 µm, respectively. The outer CCT layers in each group were 195±75, 214±83, 189±58, 228±77, and 201±70 µm, respectively. Total CCT and the outer layer in DME+DT-was significantly thicker than the DME-DT+group (each P < 0.05). In contrast, there was no significant difference in inner layer between the groups. CONCLUSIONS: The total and outer CCT layers of diabetic eyes were significantly thickened in the DME+DT-as compared with the DME-DT+group, suggesting that CCT may be related to the pathology of DME.

Alteration of choroidal vascular structure in diabetic retinopathy.

PURPOSE: The aim of this study was to analyse choroidal structures in normal patients and patients with diabetes with various severities of diabetic retinopathy (DR). METHODS: This is a retrospective observation case control study. Three hundred and forty-two diabetic eyes, and age-matched 112 eyes without diabetes mellitus (DM) were enrolled in this study. Patients with DM were classified into no DR, mild/moderate non-proliferative DR (mNPDR), severe NPDR and proliferative DR (PDR). Patients with DM were further divided into two groups based on information regarding systemic DM treatment situation: DM-treated and untreated groups. Central choroidal thickness (CCT), and total choroidal area (TCA), luminal area (LA) and stromal area (SA) were determined using enhanced depth imaging optical coherence tomography and a binarisation method, respectively. The ratio of LA in the TCA was defined as L/C ratio. RESULTS: The haemoglobin A1c (HbA1c) value was significantly higher in the DM-untreated than in the DM-treated subjects. L/C ratio was significantly lower in all the diabetic eyes than control eyes (p<0.05). TCA, LA, L/C ratio and CCT were significantly greater in the DM-untreated than treated group (each p<0.05). In the DM-untreated group, TCA and LAs (p<0.05) and L/C ratio (p<0.01) were significantly lower in mNPDR subjects than normal controls (p<0.05). PDR in the DM-untreated group showed significantly larger SA and LA, and greater CCT than normal controls (each p<0.05). CONCLUSIONS: These results suggest that choroidal vasculature was initially involved at an early DR, whereas thickened LA and SA were noted in advanced DR.

Electrostatically Driven Guest Binding in Self-Assembled Molecular Network of Hexagonal Pyridine Macrocycle at the Liquid/Solid Interface: Symmetry Breaking Induced by Coadsorbed Solvent Molecules.

We present here the construction of a self-assembled two-dimensional network at the liquid/solid interface using a hexagonal pyridine macrocycle which binds an organic cation in its intrinsic porous space by electrostatic interactions. For this purpose, a hexagonal pyridinylene-butadiynylene macrocycle (PyBM) having six octyloxymethyl groups, PyBM-C8, was synthesized. As guests, tropylium (Tr) tetrafluoroborate and trioxatriangulenium (TOTA) hexafluorophosphate were used. In this study, we focused on (i) the network patterns of PyBM-C8 which change in response to its concentration and (ii) the position of the guest immobilized in the porous space of the macrocycle. Scanning tunneling microscopy (STM) observations at the interface of 1,2,4-trichlorobenzene (TCB) and highly oriented pyrolytic graphite (HOPG) revealed that PyBM-C8 formed four different polymorphs, oblique, loose hexagonal, linear, and rectangular, depending on the solute concentration and annealing treatment. Solvent TCB molecules are likely coadsorbed to not only the intrinsically porous space of PyBM-C8 (internal TCB) but also the space outside of the macrocycle between its alkyl chains (external TCB) in most of the cases. Upon adding the guest cation, whereas small Tr was not visualized in the pore due to size mismatching, larger TOTA was clearly observed in each pore. In addition, based on high-resolution STM images of the rhombus packing pattern of PyBM-C8, we revealed experimentally that TOTA was placed at an off-center position of the deformed hexagonal macrocyclic core in the rhombus pattern. On the basis of the molecular mechanics calculations, we hypothesize that the off-center location of TOTA is due to deformation of the hexagonal macrocycle through interaction with two external TCB molecules located at opposite edges of the macrocyclic core. Symmetry breaking of the macrocyclic host framework induced by coadsorbed surrounding solvent molecules thus plays a significant role in host-guest complexation at the liquid/solid interface.

Relationship between choroidal structure and duration of diabetes.

BACKGROUND: The aim of this study was to evaluate the relationship between the choroidal structure of diabetic patients without diabetic retinopathy (DR) and duration of diabetes. METHODS: This study is a retrospective observational study in diabetic patients without DR. Eyes with diabetes mellitus (DM) (n = 105) were divided into two groups based on the duration: long duration group (over 10 years, n = 31) and short duration group (less than 10 years, n = 74). One hundred seventeen eyes of non-diabetic patients were used as control group. All patients underwent enhanced depth imaging optical coherence tomography, and the choroidal structure was analyzed using a binarization method. RESULTS: There was no significant difference in areas of total choroid and lumina/stroma or central choroidal thickness (CCT) between control and DM groups. In contrast, lumina/total choroidal (L/C) ratio was significantly lower in diabetic eyes than in control eyes (P = 0.02). Although there was no significant difference in the areas or CCT between short and long duration groups, L/C ratio was significantly lower in the long duration group than in the short duration group (P = 0.03). CONCLUSIONS: The current study suggests that choroidal vasculature is involved in the diabetic eyes and that the choroidal structure has changed with duration of diabetes. Our study points out that L/C ratio is a new potential biomarker in monitoring choroidal vascular disorders in diabetic eyes without DR.

Alteration of layer thickness in the choroid of diabetic patients.

IMPORTANCE: Choroidal thickness changes in diabetic retinopathy improve the understanding of the pathophysiology and managements of this disease. BACKGROUND: To examine the choroidal layer thickness in diabetes mellitus (DM) patients and normal individuals, and to compare the findings based on medical history of systemic DM treatments, and stage of diabetic retinopathy (DR). DESIGN: Case control study. PARTICIPANTS: Two hundred and sixty-eight eyes of 134 DM patients and age-matched 72 healthy controls of 92 eyes. METHODS: Central choroidal layer thickness (total, inner and outer layers) was measured using enhanced depth imaging OCT. DM patients were divided into two groups; the DM-treated group (88 cases), and the untreated group (46 cases). These two groups were further classified into four groups; no DR (NDR), mild/moderate non-proliferative DR (mNPDR), severe NPDR and PDR. MAIN OUTCOME MEASURES: Comparison of subfoveal choroid layer thickness in control and diabetic patient groups. RESULTS: Choroidal thickness measurements of diabetic eyes had strong correlation between masked raters in choroidal layers, proving high reproducibility. The total and outer choroid thicknesses in mNPDR in the DM-untreated group were significantly thinner than normal controls (each P < 0.05). Choroidal outer layer thickness of the severe NPDR in the DM-untreated group was significantly thicker than normal controls (P < 0.05). In the DM treatment group, there were no significant differences from the control group regarding choroidal layer thicknesses and all stages of DR. CONCLUSIONS AND RELEVANCE: The choroidal thickness significantly changed in the DM-untreated group, and the main anatomical changes might result from the outer layer.

Alteration of layer thickness in the choroid of diabetic patients.

IMPORTANCE: Choroidal thickness changes in diabetic retinopathy improve understanding the pathophysiology and managements of this disease. BACKGROUND: To examine the choroidal layer thickness in diabetes mellitus (DM) patients and normal individuals, and to compare the findings based on medical history of systemic DM treatments, and stage of diabetic retinopathy (DR). DESIGN: Case control study. PARTICIPANTS: Two hundred sixty eight eyes of 134 DM patients and age-matched 72 healthy controls of 92 eyes. METHODS: Central choroidal layer thickness (total, inner, and outer layers) was measured using enhanced depth imaging OCT. DM patients were divided into two groups; the DM treated group (88 cases), and the untreated group (46 cases). These two groups were further classified into four groups; no DR (NDR), mild/moderate non-proliferative DR (mNPDR), severe NPDR and PDR. MAIN OUTCOME MEASURES: Comparison of subfoveal choroid layer thickness in control and diabetic patient groups. RESULTS: Choroidal thickness measurements of diabetic eyes had strong correlation between masked raters in choroidal layers, proving high reproducibility. The total and outer choroid thicknesses in mNPDR in the DM untreated group were significantly thinner than normal controls (each P<0.05). Choroidal outer layer thickness of the severe NPDR in the DM untreated group was significantly thicker than normal controls (P<0.05). In the DM treatment group, there were no significant differences from the control group regarding choroidal layer thicknesses and all stages of DR. CONCLUSIONS AND RELEVANCE: The choroidal thickness significantly changed in the DM untreated group, and the main anatomical changes might result from the outer layer.

Choroidal thickness in diabetic retinopathy in relation to long-term systemic treatments for diabetes mellitus.

PURPOSE: To measure central choroidal thickness (CCT) in patients with diabetic retinopathy (DR) and analyze the correlation with clinical backgrounds regarding medications for diabetes mellitus (DM). METHODS: We retrospectively identified 86 patients with DR (172 eyes) and 43 healthy subjects (57 eyes) who underwent spectral-domain optical coherence tomography. Among the 86 patients with DM who had received no intraocular treatments, 61 were diabetic patients who had continuously received systemic treatments for DM (under treatment group). Twenty-five were patients who had discontinued the treatments or had not received any treatment for DM until this study started (no treatment group). RESULTS: The results of CCT acquired by 2 masked raters showed a significant correlation coefficient (r = 0.98), indicating high reproducibility in this study. No correlation of CCT was noted between normal (272 ± 71 µm) and DM eyes (264 ± 77 µm), the presence of diabetic macular edema, or CCT and the severity of DR in the patients examined. Interestingly, there was a significant decrease in CCT (175 ± 42 µm) in eyes with mild/moderate nonproliferative DR (NPDR) in the no treatment group (p<0.05), whereas CCT was prominently thicker in eyes with severe NPDR (354 ± 76 µm) and proliferative DR (286 ± 74 µm) than in eyes without DR. CONCLUSIONS: This study demonstrated that CCT was significantly decreased in the presence of mild/moderate NPDR in the no treatment group, suggesting that a continuously high blood sugar state caused by insufficient treatments for DM may facilitate vascular damage in the choroid in the early stage of DR.

Measurement of interleukins in vitreous infusion fluid.

Measurements of interleukin (IL)-6 and -10 concentrations in the vitreous can be used to differentiate intraocular lymphoma (IOL) from uveitis. This is the first study reporting the IL-6 and -10 concentrations in the undiluted vitreous fluid and vitreous infusion fluid, which were simultaneously examined in the patients. A total of 2 females presented with intraocular inflammation, and underwent pars plana vitrectomy. Undiluted anterior vitreous and vitreous infusion fluid were collected simultaneously. IL concentrations were determined by enzyme-linked immunosorbent assay systems. Vitreous infusion fluid of 20 ml was eventually collected following completion of core vitrectomy in the two patients. IL-6 concentrations of the first patient were 513 and 106 pg/ml in the undiluted vitreous and the infusion fluid, respectively, while those of the second patient were 263 and 29 pg/ml. By contrast, IL-10 was under the detectable levels in all the fluids. The IL-10/-6 ratio was <1 in both fluids in the patients. Cytological examination revealed the presence of reactive inflammatory cells in the vitreous fluid. The two patients were eventually diagnosed with uveitis. Measurements of IL concentrations in the vitreous infusion fluid provided significant evidence on the differential diagnosis between IOL and uveitis, when considering how vitreous infusion fluid was diluted. The present study highlighted a novel application of cytokine analyses using the vitreous infusion fluid, which may contribute to the development of future translational researches on uveitis/IOL patients.

Bilateral Neuroretinitis in Cat Scratch Disease with Exudative, Obliterative Vasculitis in the Optic Disc.

A 29-year-old fisherman exhibited optic disc oedema and peripapillary retinal detachment in the right eye, whereas in the left eye, optic atrophy and intraretinal exudates were already observed on first examination. About 6 months earlier, he noticed blurred vision of the left eye but took no medication. Visual acuity was 0.4 OD and 0.01 OS. Perimetry showed a large lower-half field defect with sparing 10° central field in the right eye and a large central scotoma in the left eye. Fluorescein angiography showed existence of arteriole or capillary nonperfusion and hyperpermeability of surrounding capillaries. Since serological examinations showed positive Bartonella immunoglobulin G (IgG) and other causes of neuroretinitis (NR) were excluded, NR in the present case was caused by cat scratch disease (CSD). Optic atrophy appeared 2 weeks after onset. Optical coherence tomography 13 weeks after onset revealed severe loss of retinal nerve fibre layer (RNFL) superior and nasal to the optic disc in both eyes and temporal in the left eye. Visual acuity of the right eye improved to 1.2 by the treatment, whereas visual field defects were persistent. CSD-NR in the present case developed abrupt appearance of optic atrophy with severe RNFL loss in the right eye, which was elicited by exudative, obliterative vasculitis in the superficial layer of the optic disc.

Retinal angiography and optical coherence tomography disclose focal optic disc vascular leakage and lipid-rich fluid accumulation within the retina in a patient with leber idiopathic stellate neuroretinitis.

A 52-year-old woman with clinical features of Leber idiopathic stellate neuroretinitis (LISN) underwent retinal fluorescein and indocyanine green angiography that revealed lipid-containing fluid leakage from a single arteriole in the superficial nerve fiber layer of the optic disc. The fluid expanded gradually into the upper half of the optic disc and the adjacent peripapillary retina. Optical coherence tomography (OCT) demonstrated fluid accumulation in two separate subretinal spaces and in the outer nuclear-plexiform layer, which extended from the optic disc margin to the fovea. These angiographic and OCT findings support the hypothesis that LISN develops from focally increased permeability of an optic disc surface arteriole from which lipid-rich fluid flows through the outer nuclear-plexiform layer space to pool in these retinal areas.

Incomplete oculomotor palsy with pupil sparing caused by compression of the oculomotor nerve by a posterior communicating posterior cerebral aneurysm.

PURPOSE: To report a patient with agenesis of both internal carotid canals who presented with incomplete oculomotor palsy with pupil sparing. METHODS: The incomplete oculomotor palsy was followed clinically, and the precise anatomical relation of the aneurysm to the subarachnoid oculomotor nerve was investigated during clipping surgery for the aneurysm. RESULTS: A 39-year-old woman with agenesis of both internal carotid arteries was admitted because of diplopia and left blepharoptosis. The left superior palpebral and the superior rectus muscles were severely palsied. The paralysis of the medial rectus muscle was milder than that of the former two muscles, and the inferior rectus was the least affected muscle. The papillary reflexes were normal. Examination during clipping surgery showed that the aneurysm was located below the oculomotor nerve in the subarachnoid space about 6.5 mm from its exit from the midbrain. The differences in severity and resolution time of the palsies of the extraocular muscles suggested that the fibers destined for the superior levator and the superior rectus were concentrated on the caudomedial portion of the subarachnoid oculomotor nerve. The fibers innervating the medial rectus muscle were located within the core of the nerve, and the fibers innervating the pupils and the inferior rectus muscle occupied a more rostral part. CONCLUSIONS: The functional distribution of fibers within the subarachnoid oculomotor nerve about 6.5 mm from its exit from the midbrain succeeds to that of the intraparenchymal oculomotor nerve.

Increased osteopontin levels in the vitreous of patients with diabetic retinopathy.

PURPOSE: Osteopontin (OPN) has diverse functions such as cell adhesion, chemoattraction, immunomodulation, and angiogenesis. The aim of this study is to analyze the OPN levels in vitreous fluid obtained from diabetic retinopathy (DR) and non-DR patients. METHODS: Nineteen patients out of 11 with DR and 8 without DR underwent pars plana vitrectomy and vitreous fluid was obtained simultaneously. Two distinct sandwich enzyme-linked immunosorbent assay systems (systems 1 and 2) were applied, which have been developed in our laboratories to quantify the OPN concentrations in vitreous fluid. RESULTS: The non-thrombin-cleaved full-length OPN levels in the vitreous fluid were 921.63 +/- 45.38 ng/ml in DR and 632.80 +/- 83.43 ng/ml in non-DR using system 1. Also, vitreous thrombin-cleaved and noncleaved OPN levels were increased to 2,109.22 +/- 151.651 and 1,651.13 +/- 229.82 ng/ml in patients with DR and non-DR using system 2. The vitreous OPN levels were significantly higher in DR than those in non-DR (p < 0.01 by system 1 and p < 0.05 by system 2). CONCLUSION: Thrombin-cleaved and noncleaved vitreous OPN levels in patients with DR were increased compared with control subjects, suggesting that OPN plays a potential role in the pathogenesis of diabetic retinal ischemia.

Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy.

PURPOSE: It is widely accepted that intravitreous levels of erythropoietin (Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aim of this study was to examine the expression of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without diabetes. METHODS: Eighteen epiretinal membranes (PDR (n = 10), idiopathic epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin-fixed and paraffin-embedded tissues were examined by immunohistochemistry with anti-Epo and EpoR antibodies. RESULTS: The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non-vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane. CONCLUSION: EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.