Stratified choroidal vascular structure in treatment-naïve diabetic retinopathy.

OBJECTIVE: To analyze the anatomical choroidal vascular layers in topical treatment-naïve diabetic retinopathy (DR) eyes. DESIGN: A retrospective, clinical case-control study. METHODS: A total of 328 eyes from 228 patients with treatment-naive DR and 192 eyes matched for axial length from 174 healthy controls were enrolled in the study. Choroidal structure was quantitatively analyzed using enhanced depth imaging optical coherence tomography (EDI-OCT). Each choroidal vascular layer was divided into the choriocapillaris, Sattler's layer, and Haller's layer, and then the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT) were calculated using binarization techniques. The ratio of LA to CA was defined as the L/C ratio. RESULTS: In the choriocapillaris, CA was significantly lower in the mild/moderate non-proliferative DR (mNPDR) group than in the control group, and SA was significantly higher in all DR groups (each P < 0.01). The L/C ratio was significantly lower in all DR groups than controls (P < 0.01). In Sattler's layer, CA, LA, and SA were significantly higher in the severe NPDR (sNPDR) and PDR groups than in the control group (P < 0.01). In Haller's layer, the L/C ratio was significantly high among the PDR groups (P < 0.05). CONCLUSIONS: The choroidal parameters of DR patients by the binarization method were associated with the stage of DR, in which the choriocapillaris lumen decreased in all the DR stages. The expansion of CA seen in more advanced DR eyes mainly resulted from changes in the Sattler's and Haller's layers.

Effects of age and axial length on choroidal stratified structure in normal eyes.

To quantify the choroidal structures of normal eyes by optical coherence tomography (OCT)-based binarization and evaluate the relationships among age, refractive power, and ocular axial length. This was a retrospective observational study. One hundred and eighty nine eyes of 189 subjects without ocular diseases were examined by enhanced depth imaging (EDI)-OCT. A choroidal OCT horizontal image with a width of 1500 µm centered on the fovea was binarized. The lumen, stroma, and total choroidal area in the choriocapillaris (CC), Sattler's layer (SL), and Haller's layer (HL) were measured, and the ratio of the luminal area to total choroidal area (L/C ratio) was calculated. Multiple regression analysis was performed for choroidal parameters in each choroidal layer and for age, refractive power, and ocular axial length. Multiple regression analysis showed that an older age was significantly correlated with a lower choroidal area and the L/C ratio in all choroidal layers (each P < 0.05). A Long axial length was significantly associated with lower SL and HL (P < 0.05), but not with refractive power. In the choroid of normal eyes, age-related decreases in the choroidal area and L/C ratio were associated with all choroidal layers, and elongation of the axial length was associated with thinning of SL and HL.

Changes in choriocapillaris structure occurring in idiopathic macular hole before and after vitrectomy.

PURPOSE: The aim of this study was to analyze the anatomical choroidal vascular layers and the changes in idiopathic macular hole (IMH) eyes over time after vitrectomy. METHODS: This is a retrospective observational case-control study. Fifteen eyes from 15 patients who received vitrectomy for IMH and age-matched 15 eyes from 15 healthy controls were enrolled in this study. Retinal and choroidal structures were quantitatively analyzed before vitrectomy and 1 and 2 months after surgery using spectral domain-optical coherence tomography. Each choroidal vascular layer was divided into the choriocapillaris, Sattler's layer, and Haller's layer, and then, the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT) were calculated using binarization techniques. The ratio of LA to CA was defined as the L/C ratio. RESULTS: The CA, LA, and L/C ratios were 36.9 ± 6.2, 23.4 ± 5.0, and 63.1 ± 7.2 in the choriocapillaris of IMH and were 47.3 ± 6.6, 38.3 ± 5.6, and 80.9 ± 4.1 in that of control eyes, respectively. Those values were significantly lower in IMH eyes than in control eyes (each P < 0.01), whereas there was no significant difference in total choroid, Sattler's layer, and Haller's layer or CCT. The ellipsoid zone defect length showed a significant negative correlation with the L/C ratio in total choroid and with CA and LA in the choriocapillaris of IMH (R = - 0.61, P < 0.05, R = - 0.77, P < 0.01, and R = - 0.71, P < 0.01, respectively). In the choriocapillaris, the LA were 23.4 ± 5.0, 27.7 ± 3.8, and 30.9 ± 4.4, and the L/C ratios were 63.1 ± 7.2, 74.3 ± 6.4, and 76.6 ± 5.4 at baseline, 1 month, and 2 months after vitrectomy, respectively. Those values showed a significant increase over time after surgery (each P < 0.05), whereas the other choroidal layers did not alter consistently with respect to changes in choroidal structure. CONCLUSIONS: The current OCT-based study demonstrated that the choriocapillaris was exclusively disrupted between choroidal vascular structures in IMH, which may correlate with the ellipsoid zone defect. Furthermore, the L/C ratio of choriocapillaris recovered after IMH repair, suggesting an improved balance between supply and demand of oxygen that has collapsed due to temporary loss of central retinal function by IMH.

Peripapillary circulatory dysfunction precedes structural loss in treatment-naive diabetic retinopathy.

PURPOSE: The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR). METHODS: One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas. RESULTS: RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters. CONCLUSIONS: Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR.

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.

Factors based on optical coherence tomography correlated with vision impairment in diabetic patients.

The aim of this study is to evaluate the relationship between retinal structures and visual acuity in diabetic patients using optical coherence tomography (OCT) and OCT angiography (OCTA). This study was a retrospective observational study conducted at a single medical center in Japan. Evaluation of retinal images was analyzed using spectral domain OCT. Twelve factors including central retinal thickness, length of disorganization of retinal inner layer (DRIL), number of inner hyperreflective foci, number of outer hyperreflective foci, height of intraretinal fluid, height of subretinal fluid, length of external limiting membrane disruption, length of external ellipsoid zone (EZ) disruption, vessel density of superficial capillary plexus (SCP), foveal avascular zone (FAZ) area, and FAZ circularity were analyzed based on OCT/OCTA findings. Multivariate analysis was used to investigate the OCT-based factors that could be correlated with poor visual acuity in treatment-naïve diabetic eyes. A total of 183 eyes of 123 diabetic patients with type 2 diabetes (mean age 61.9 ± 12.3 years, 66 men and 57 women) and 62 eyes of 55 control subjects (mean age 64.4 ± 12.5 years, 15 men and 40 women) was enrolled in this study. Multiple regression analysis showed that OCT-based factors correlated with visual acuity were length of DRIL (ß = 0.24, P < 0.01), length of EZ disruption (ß = 0.35, P < 0.001), and FAZ circularity (ß = - 0.14, P < 0.05). The other factors showed no significant correlation. In conclusion, the length of DRIL, length of EZ disruption, and FAZ circularity measured by OCT were identified as related factors for visual impairment in treatment-naïve diabetic eyes.

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.

Spherulitic Crystallization in Langmuir-Blodgett Films of the Ditetradecyldimethylammonium-Au(dmit)2 Salt.

Spherulitic crystallization in Langmuir-Blodgett (LB) films of the ditetradecyldimethylammonium-Au(dmit)2 [2C14N+Me2-Au(dmit)2] salt has been characterized by polarized light microscopy, Fourier-transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD) analyses. Analyses by differential scanning calorimetry (DSC) for the bulk crystals indicate that annealing in the temperature range of 58-100 °C may be appropriate to improve the order in the LB film. The polarized light microscopy measurement further revealed that a spherulite structure was formed after the film was annealed at 80 °C for 60 min. FT-IR spectroscopy measurements demonstrated that the order of the principal hydrocarbon chains was improved and that the rotation of CH3 groups was hindered by the annealing. Out-of-plane XRD analyses revealed that the d-spacing of the 2C14N+Me2-Au(dmit)2 LB film changed from 3.1 to 2.5 nm upon annealing. We hypothesize that a layered structure with interdigitated hydrocarbon chains, which is equivalent to or close to that of the corresponding bulk crystal, has been realized in the LB film by annealing. We consider that two different kinds of one-dimensional (1D) interactions along the a-axis are the driving forces to realize the spherulite structure in the LB system; one is an extended 1D contact due to the pronounced interdigitation of the alkyl chains of the ammonium ion, which plays a role similar to that of the folding of chains in the lamellar structures of polymers, and the other is a 1D extended sulfur-sulfur contact between Au(dmit)2 dimer pairs. So far, spherulite formation in LB films has been reported almost exclusively for polymerized materials. Here, we demonstrate that a spherulite texture can also be formed in LB films based on nonpolymerized materials via the interdigitation of hydrocarbon chains, leading to a new well-ordered state.

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.

Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

Microsomal prostaglandin E synthase-1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease-like pathology in a mouse model.

Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity can moderate the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E2 (PGE2 ), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. Here we found that, among three PGES enzymes, only microsomal PGES-1 (mPGES-1) is induced, and its expression is associated with ß-amyloid (Aß) plaques in the cerebral cortex in human AD patients and in Tg2576 mice, a transgenic AD mouse model. Furthermore, to investigate whether mPGES-1 contributes to AD-like pathology, we bred mPGES-1-deficient mice with Tg2576 mice. We found that mPGES-1 deletion reduced the accumulation of microglia around senile plaques and attenuated learning impairments in Tg2576 mice. These results indicated that mPGES-1 is induced in the AD brain and thus plays a role in AD pathology. Blockage of mPGES-1 could form the basis for a novel therapeutic strategy for patients with AD.

SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.

To discover susceptibility genes of late-onset Alzheimer's disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2×10(-5) were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P = 7.33×10(-7) in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P = 1.77×10(-9)) and rs3781834 (P = 1.04×10(-8)). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P = 1.71×10(-5)) and rs744373 near BIN1 (P = 1.39×10(-4)). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations.

A highly sensitive and temporal visualization system for gaseous ethanol with chemiluminescence enhancer.

A two-dimensional gaseous ethanol visualization system has been developed and demonstrated using a horseradish peroxidase-luminol-hydrogen peroxide system with high-purity luminol solution and a chemiluminescence (CL) enhancer. This system measures ethanol concentrations as intensities of CL via the luminol reaction. CL was emitted when the gaseous ethanol was injected onto an enzyme-immobilized membrane, which was employed as a screen for two-dimensional gas visualization. The average intensity of CL on the substrate was linearly related to the concentration of standard ethanol gas. These results were compared with the CL intensity of the CCD camera recording image in the visualization system. This system is available for gas components not only for spatial but also for temporal analysis in real time. A high-purity sodium salt HG solution (L-HG) instead of standard luminol solution and an enhancer, eosin Y (EY) solution, were adapted for improvement of CL intensity of the system. The visualization of gaseous ethanol was achieved at a detection limit of 3 ppm at optimized concentrations of L-HG solution and EY.