C1q Binding Ability for Prior Risk Assessment of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

In ABO blood group incompatible kidney transplantation (ABO-I), potential issues on acute antibody-mediated rejection (ABMR) remain to be solved. This study aimed to assess the risk factors of acute ABMR using recipient- or donor-derived specimens. Quantitative analysis of A/B antigen expression was conducted in 104 donor kidney tissues (Kt), platelets (Plt), and red blood cells (RBC) by immunohistochemical staining or flow cytometry (FCM). ABO-I pre-transplant recipient serum samples (ABMR = 12, non-ABMR = 27) were extracted by propensity score matching. Anti-A antibody titers of IgM, IgG and IgG subclasses, and C1q binding ability (%) on antibody were measured using RBC-FCM. No association was observed between ABMR and A/B antigen expression levels in donor's Plt, RBC, or Kt. In recipient's sample, C1q-IgG binding ability was significantly higher in the ABMR group than in the non-ABMR group (C1q-IgG: 9.04% vs. 5.93% p = 0.049). Neither the A/B antigen expression level in donors (grafts) nor anti-blood group IgG/IgM antibodies in recipient sera before desensitization seemed to influence ABMR incidence in ABO-I. In contrast, C1q-IgG binding ability could be a potential predictor for ABMR in ABO-I.

Human RP105 monoclonal antibody enhances antigen-specific antibody production in unique culture conditions.

Detecting antibodies, particularly those targeting donor human leukocyte antigens in organ transplantation and self-antigens in autoimmune diseases, is crucial for diagnosis and therapy. Radioprotective 105 (RP105), a Toll-like receptor family protein, is expressed in immune-competent cells, such as B cells. Studies in mice have shown that the anti-mouse RP105 antibody strongly activates B cells and triggers an adjuvant effect against viral infections. However, the anti-human RP105 antibody (ɑhRP105) weakly activates human B cells. This study established new culture conditions under, which human B cells are strongly activated by the ɑhRP105. When combined with CpGDNA, specific antibody production against blood group carbohydrates, ɑGal, and SARS-CoV-2 was successfully detected in human B cell cultures. Furthermore, comprehensive analysis using liquid chromatography-electrospray ionization tandem mass spectrometry, single-cell RNA sequencing, and quantitative real-time PCR revealed that ɑhRP105 triggered a different activation stimulus compared to CpGDNA. These findings could help identify antibody-producing B cells in cases of transplant rejection and autoimmune diseases.

Blood compatibility of poly(propylene glycol diester) and its water structure observed by differential scanning calorimetry and 2H-nuclear magnetic resonance spectroscopy.

Recently, we applied solution 2H-nuclear magnetic resonance spectroscopy (2H NMR) to analyze the water (deuterium oxide, D2O) structure in several biopolymers at ambient temperature. We established that polymers with good blood compatibility (i.e. poly(2-methoxyethyl acrylate) (PMEA)) have water observed at high magnetic fields (upfield) compared with bulk water. Polymers containing poly(propylene glycol) (PPG) or poly(propylene oxide) (PPO) exhibit good compatibility; however, the reason for this remains unclear. In addition, reports on the blood compatibility of PPO/PPG are limited. Therefore, PPG diester (PPGest) was prepared as a model polymer, and its blood compatibility and water structure were investigated. PPGest exhibited excellent blood compatibility. The water in PPGest was observed upfield by 2H NMR, and it was defined as non-freezing water via differential scanning calorimetry. Based on these observations, the relationship between the blood compatibility and water structure of PPGest is discussed by comparing with those of PMEA, and the reason for the good performance of PPG/PPO-based polymers is discussed.

A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

Isohemagglutinin assays employing red blood cells (RBCs) are the most common assays used to measure antibody titer in ABO-incompatible kidney transplantation (ABOi KTx). However, ABO antigens expressed on RBCs are not identical to those of kidney and antibody titers do not always correlate with clinical outcome. We previously reported that CD31 was the main protein linked to ABO antigens on kidney endothelial cells (KECs), which was different from those on RBCs. We developed a new method to measure antibody titer using a microarray of recombinant CD31 (rCD31) linked to ABO antigens (CD31-ABO microarray). Mass spectrometry analysis suggested that rCD31 and native CD31 purified from human kidney had similar ABO glycan. To confirm clinical use of CD31-ABO microarray, a total of 252 plasma samples including volunteers, hemodialysis patients, and transplant recipients were examined. In transplant recipients, any initial IgG or IgM antibody intensity >30,000 against the donor blood type in the CD31-ABO microarray showed higher sensitivity, specificity, positive predictive value, and negative predictive value of AABMR, compared to isohemagglutinin assays. Use of a CD31-ABO microarray to determine antibody titer specifically against ABO antigens expressed on KECs will contribute to precisely predicting AABMR or preventing over immunosuppression following ABOi KTx.

Comparative study on water structures of poly(tetrahydrofurfuryl acrylate) and poly(2-hydroxyethyl methacrylate) by nuclear magnetic resonance spectroscopy.

It is well known that poly(2-methoxyethyl acrylate) (PMEA) has good blood compatibility and its performance is attributed to its water structure. Recently, we applied solution nuclear magnetic resonance spectroscopy (solution-NMR) for analyzing the water structure in PMEA at ambient temperature and concluded that this method is useful because of the clear observation of the resonance peaks at low and high magnetic field (downfield and upfield, respectively) areas indicating the existence of more than two types of water. The present study was performed to compare the water structure of poly(tetrahydrofurfuryl acrylate) (PTHFA) and poly(2-hydroxyethyl methacrylate) (PHEMA) using solution 2H-NMR and deuterium oxide as water at the temperature range 15-45 °C. It was found that PTHFA has a different water structure from that of PHEMA. Water in PTHFA clearly showed two resonance peaks at downfield and upfield areas, with different spin-lattice relaxation times, T12H (high and low values, respectively). These observations are similar to those of PMEA. In contrast, PHEMA showed only one broad resonance peak (at downfield) with a low T12H value. Based on these observations, this study discusses the effect of water structures on the blood compatibility of these polymers.

Improved detection of donor-specific HLA-class II antibody in kidney transplant recipients by modified immunocomplex capture fluorescence analysis.

Immunocomplex capture fluorescence analysis (ICFA) which basic principle is same as Luminex crossmatch (LXM), could detect donor-specific HLA antibody (DSA). The advantages of ICFA are (i) detection of DSA and (ii) no requirement of viable cells over the flow cytometry crossmatch (FCXM). However, FCXM has been widely used because of its higher sensitivity than ICFA, in particular HLA-class II antibody detection. In this study the accuracy of DSA detection against HLA-class II was investigated by modifying the original method of ICFA. Increment of the sensitivity was found when purified peripheral blood mononuclear cells (PBMCs) were used instead of whole blood. An ICFA-PBMC in addition to FCXM-T/B was conducted for 118 patients before kidney transplantation and 13 patients with de novo DSA against HLA-class II after transplantation. Significantly positive correlation was observed between the values of ICFA-PBMC and DSA mean fluorescence intensity (MFI) targeting class II (p < 0.0001). When the cutoff level of 1.4 was determined by receiver operating characteristic curve analysis, the average DSA MFI was found to be significantly higher in the ICFA-PBMC (class II) positive group comparing to that in the negative group (12,217 vs 3885, p = 0.0027). ICFA-PBMC and optimized cutoff level could provide valid information in cases of suspected DSA.

NONPERFUSION AREA QUANTIFICATION IN BRANCH RETINAL VEIN OCCLUSION: A Widefield Optical Coherence Tomography Angiography Study.

PURPOSE: To precisely quantify retinal nonperfusion areas (NPAs) in branch retinal vein occlusion using widefield optical coherence tomography angiography (OCTA) and examine their association with neovascular complications. METHODS: We enrolled 26 patients with treatment-naïve branch retinal vein occlusion and prospectively examined them for 12 months. After 3 monthly ranibizumab injections to treat macular edema, each patient underwent ultra-widefield (UWF) fluorescein angiography (FA) and OCTA. Ultra-widefield FA was additionally performed at Month 12. For UWF FA, the retinal NPA was measured using the equipment's built-in software. For OCTA, we used panoramic image montaged from 5 single 12 × 12 mm2 images and quantified the retinal NPA using a Gullstrand eye with a grid scale at each patient. Measurements were expressed in terms of actual values and disc area units. RESULTS: The retinal NPAs as measured using single OCTA and panoramic OCTA were significantly associated with that measured using UWF FA (P < 0.001 for both). Retinal neovascularization lesions were observed in 4 (15.4%) of 26 eyes. For patients with accompanying neovascularization, the retinal NPA measured using UWF FA, single OCTA, and panoramic OCTA were 187.9 ± 39.5 mm2 (109.9 ± 21.4 disc area), 34.3 ± 13.7 mm2 (19.9 ± 7.7 disc area), and 106.6 ± 24.5 mm2 (62.4 ± 13.6 disc area), respectively, which were larger than for those without neovascularization (P < 0.001, 0.014, and <0.001, respectively). CONCLUSION: Using widefield OCTA, we could quantify the retinal NPA of eyes with branch retinal vein occlusion. These could serve as valid references to assess the risk of neovascular complications.

ANGIOGRAPHIC RISK FACTORS FOR RECURRENCE OF MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To examine angiographic risk factors for the recurrence of macular edema associated with branch retinal vein occlusion. METHODS: We consecutively included 51 patients with treatment-naive branch retinal vein occlusion involving the macular area. Each eye initially received 3 monthly ranibizumab injections, with additional injections as necessary. At Month 3, we examined parafoveal vessel diameter indexes (VDI) in all sectors using optical coherence tomography angiography and determined the association with retinal thickness changes (Month 3-Month 5) and the number of ranibizumab injections during 12 months. RESULTS: Parafoveal VDIs in the affected, nasal, and temporal sectors at Month 3 were significantly associated with corresponding parafoveal thickening (P = 0.020, 0.010, and <0.001, respectively), and the parafoveal VDIs in the affected and temporal sectors were significantly associated with future foveal thickening (P = 0.037, and 0.026, respectively). Moreover, the parafoveal VDI in the temporal sector showed a significant association with the total required number of ranibizumab injections (P = 0.040). CONCLUSION: The parafoveal VDI may adequately represent the degree of congestion associated with branch retinal vein occlusion. Particularly, the VDI in the temporal sector may be a good predictor of future retinal thickening in the corresponding parafovea and the fovea and the number of ranibizumab injections.

Factors associated with extremely poor visual outcomes in patients with central retinal vein occlusion.

Here, we examined prognostic factors for extremely poor visual outcomes in patients with central retinal vein occlusion (CRVO) in actual practices. We included 150 consecutive eyes with treatment-naïve acute CRVO from four different facilities and observed them for over 24 months. Macular edema (ME) was treated with one or three monthly anti-vascular endothelial growth factor injections (1 or 3 + pro re nata). According to the final Snellen visual acuity (VA), we divided the patients into very poor VA (< 20/200) and control (≥ 20/200) groups and examined risk factors for poor final visual outcomes. The baseline Snellen VA was hand motion to 20/13. The mean number of anti-VEGF injections for ME was 5.3 ± 3.7 during the follow-up period. In total, 49 (32.7%) patients exhibited a very poor final VA; this group comprised significantly older patients with a significantly poorer baseline VA (P < 0.01 for both) than the control group. Comorbid internal carotid artery disease and diabetic retinopathy were significantly associated with a poor final VA. In actual clinical practice, visual outcomes may be extremely poor despite ME treatment in certain patients with CRVO, with advanced age, poor baseline VA, and comorbid internal carotid artery disease and diabetic retinopathy being significant risk factors.

Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study.

Risk prediction of de novo donor specific antibody (DSA) would be very important for long term graft outcome after organ transplantation. The purpose of this study was to elucidate the association of eplet mismatches and predicted indirectly recognizable HLA epitopes (PIRCHE) scores with de novo DSA production. Our retrospective cohort study enrolled 691 living donor kidney transplantations. HLA-A, B, DRB and DQB eplet mismatches and PIRCHE scores (4 digit of HLA-A, B, DR, and DQ) were determined by HLA matchmaker (ver 2.1) and PIRCHE-II Matching Service, respectively. Weak correlation between eplet mismatches and PIRCHE scores was identified, although both measurements were associated with classical HLA mismatches. Class II (DRB+DQB) eplet mismatches were significantly correlated with the incidence of de novo class II (DR/DQ) DSA production [8/235 (3.4%) in eplet mismatch ≤ 13 vs. 92/456 (20.2%) in eplet mismatch ≥ 14, p < 0.001]. PIRCHE scores were also significantly correlated with de novo class II DSA production [26/318 (8.2%) in PIRCHE ≤ 175 vs. 74/373 (19.8%) in PIRCHE ≥ 176, p < 0.001]. Patients with low levels of both class II eplet mismatches and PIRCHE scores developed de novo class II DSA only in 4/179 (2.2%). Analysis of T cell and B cell epitopes can provide a beneficial information on the design of individualized immunosuppression regimens for prevention of de novo DSA production after kidney transplantation.

Interferon-γ-induced HLA Class II expression on endothelial cells is decreased by inhibition of mTOR and HMG-CoA reductase.

In organ transplantation, donor-specific HLA antibody (DSA) is considered a major cause of graft rejection. Because DSA targets primarily donor-specific human leukocyte antigen (HLA) expressed on graft endothelial cells, the prevention of its expression is a possible strategy for avoiding or salvaging DSA-mediated graft rejection. We examined the effect of various clinically used drugs on HLA class II expression on endothelial cells. Interferon-γ (IFN-γ)-induced HLA class II DR (HLA-DR) was downregulated by everolimus (EVR, 49.1% ± 0.8%; P < 0.01) and fluvastatin (FLU, 33.8% ± 0.6%; P < 0.01). Moreover, the combination of EVR and FLU showed a greater suppressive effect on HLA-DR expression. In contrast, cyclosporine, tacrolimus, mycophenolic acid, and prednisolone did not exhibit any significant suppressive effect. FLU, but not EVR, suppressed mRNA of HLA-DR. Imaging analysis revealed that HLA-DR expressed in cytosol or on the cell surface was repressed by EVR (cytosol: 58.6% ± 4.9%, P < 0.01; cell surface: 80.9% ± 4.0%, P < 0.01) and FLU (cytosol: 19.0% ± 3.4%, P < 0.01; cell surface: 48.3% ± 4.8%, P < 0.01). These data indicated that FLU and EVR suppressed IFN-γ-induced HLA-DR expression at the transcriptional and post-translational level, respectively, suggesting a potential approach for alleviating DSA-related issues in organ transplantation.

Water structure of poly(2-methoxyethyl acrylate) observed by nuclear magnetic resonance spectroscopy.

Poly(2-methoxyethyl acrylate) (PMEA) is known to show excellent blood compatibility. The performance of PMEA has been attributed to the existence of cold-crystallizable water in it, as observed using differential scanning calorimetry (DSC). However, little is known on the property of the water in PMEA above 0 °C, especially at ambient temperature including the body temperature, because blood compatibility is observed at 37 °C. The present study was performed to clarify the state of water in PMEA in the temperature range 15-45 °C using solution nuclear magnetic resonance spectroscopy (NMR). In addition, water in poly(butyl acrylate) (PBA), which exhibited poor blood compatibility, was used as a control. In the NMR spectra of water in PMEA, two peaks appeared at 4.87 ppm and 3.71 ppm at 30 °C, showing the existence of two types of water structures. The peak intensity of the upfield water was considerably higher than that of the downfield water. On the other hand, the hydrated PBA showed only one peak at 4.98 ppm at 30 °C. The dynamic property of water in these polymers was estimated from the deuterium solution NMR spin-lattice relaxation time, T12H. The T12H values of peaks observed at 4-5 ppm were relatively high, denoting rapid motion, while those of water at 3.7 ppm in PMEA were small, denoting slow mobility. Thus, the states of water molecules in PMEA in terms of chemical shift and mobility were considered different from those in PBA at ambient temperature.

Angiographic Risk Features of Branch Retinal Vein Occlusion Onset as Determined by Optical Coherence Tomography Angiography.

Purpose: Examine associations between the vasculature at arteriovenous (AV) crossings and the onset of branch retinal vein occlusion (BRVO). Methods: We included 78 patients with major BRVO, 35 patients with macular BRVO, and 110 controls without BRVO and determined the vessel positions at AV crossings, where the first- or second-order branches of the retinal veins associate, using a viewing angle of 12 × 12 mm2 in optical coherence tomography angiography (OCTA). Results: We reviewed 1349 and 1276 AV crossings in BRVO patients and control subjects, respectively. The proportions of venous overcrossing were 26.5%, 28.6%, and 26.8% at non-causative crossings in BRVO eyes, non-BRVO fellow eyes, and unaffected control eyes, respectively; however, the rate of venous overcrossings at the causative crossings was 45.1%. In OCTA analyses, we divided the branches into macular- or non-macular veins. The rate of venous overcrossing was 52.5% at causative crossings in major BRVO but was 28.6% in macular BRVO. Odds ratios for whether venous overcrossing was a risk factor for BRVO were 3.09 (95% confidence interval [CI], 1.96-4.88) and 0.94 (95% CI, 0.44-2.00) for non-macular veins and macular veins, respectively. The patients with major BRVO caused by venous overcrossing were younger than patients for whom the cause was arterial overcrossing (P < 0.001). The onset of macular BRVO did not differ between crossing patterns at causative crossings (P = 0.60). Conclusions: In eyes with BRVO, venous overcrossing was a common angiographic feature at causative crossings and might be a risk factor for major BRVO onset.

Suppressive Effect of Everolimus on IL-2, IL-10, IL-21, and IFNγ Levels: Implications for the Successful Minimization of Calcineurin Inhibitor Use in Transplantation.

BACKGROUND: Success with calcineurin inhibitors (CNIs) such as cyclosporine A (CSA) and tacrolimus (TAC) in organ transplantation has demonstrated that cytokine suppression is a key factor in patient management. However, the exact effects of recently introduced immunosuppressive agents other than CNI on cytokine expression remain unknown. In this study, the action of the mTOR-inhibitor everolimus (EVR) and that of the antimetabolite mycophenolic acid (MPA) on the transcription of several cytokines was investigated. METHODS: Peripheral blood mononuclear cells obtained from healthy volunteers were stimulated with anti-CD3/28 microbeads in the presence of CSA, TAC, EVR, and/or MPA for 8 hours. The mRNA levels of each cytokine were measured using quantitative real-time polymerase chain reaction. RESULTS: MPA had no inhibitory effect on any of the cytokines tested. EVR showed moderate inhibition of IL-2, IL-10, IL-21, and IFNγ levels. These cytokines were further analyzed to investigate the additive effect of EVR in combination with CNI. The beneficial effect of EVR addition was seen at low concentrations of CSA or TAC, while no additive effect was observed at high concentrations. CONCLUSIONS: EVR might effectively inhibit the activation of recipient immune cells in combination with a low dose of CNI, maximizing clinical benefit by preventing graft rejection and alleviating CNI-induced adverse effects.

Branch Retinal Vein Occlusion: Treatment Outcomes According to the Retinal Nonperfusion Area, Clinical Subtype, and Crossing Pattern.

This prospective study examined 58 eyes with branch retinal vein occlusion (BRVO) to investigate the effects of the nonperfusion area (NPA), clinical subtype, and crossing pattern on the 2-year outcomes of ranibizumab therapy for the macular edema (ME). All eyes received three initial monthly injections, followed by additional pro re nata (PRN) injections. The final best corrected visual acuity (BCVA) and ranibizumab injection number were not associated with the macular NPA or total NPA at baseline or month 12, and they showed no significant differences between the clinical subtypes. However, the incidence of neovascular changes was higher in the major BRVO group than in the macular BRVO group (P = 0.030). Twelve and 19 of the 34 eyes with major BRVO exhibited arterial overcrossing and venous overcrossing, respectively. At baseline, the total NPA did not differ according to the crossing pattern, however, the total NPA was significantly larger in the venous overcrossing group at month 12 (P = 0.047). At month 24, the incidence of neovascular changes was higher in the venous overcrossing group (P = 0.030). Following ranibizumab therapy for BRVO-associated ME, the clinical subtype and the arteriovenous crossing pattern may be associated with neovascular changes.

FIXATION STATUS AFTER RESOLUTION OF MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate fixation status of eyes with branch retinal vein occlusion (BRVO) and to investigate its association with other clinical parameters. METHODS: This study included 57 consecutive eyes with BRVO after resolution of macular edema. Fixation status was determined by microperimetry. Defect length of the foveal ellipsoid zone band was measured by optical coherence tomography, and retinal perfusion status was assessed by optical coherence tomography angiography. RESULTS: In microperimetry, the mean fixation rate around the gravitational center of all fixation points (defined as the fixation center) was found to be 79.8 ± 18.9%, which was significantly associated with defect length of the foveal ellipsoid zone band (P < 0.001) and distance between the foveal and fixation centers (P = 0.012). The integrity of the ellipsoid zone band at the fixation center was intact in 55 eyes (96.5%). Fixation centers were located within and outside the foveal avascular zone in 33 (57.9%) and 24 (42.1%) eyes, respectively; among the latter eyes, all fixation centers were perfused. Downward deviation of fixation points was rare, despite variations in the occluded area; there was a significant difference in distribution of deviation between eyes with superotemporal and inferotemporal BRVO (P < 0.001). CONCLUSION: In eyes with BRVO, fixation status was strongly associated with visual acuity, morphologic damage, and retinal perfusion status both in the foveal area and at the fixation center after resolution of macular edema. This information regarding fixation status could facilitate vision management in patients with BRVO.

Increased CD40L+PD-1+ follicular helper T cells (Tfh) as a biomarker for predicting calcineurin inhibitor sensitivity against Tfh-mediated B-cell activation/antibody production after kidney transplantation.

It is unclear to what extent the development of follicular helper T cells (Tfh) and de novo donor-specific human leukocyte antigen antibody (DSA) production could be influenced by immunosuppressive agents, particularly calcineurin inhibitor (CNI; cyclosporine or tacrolimus), after kidney transplantation. Here, the effects of immunosuppressive agents on Tfh-mediated B-cell activation and antibody production were investigated. In vitro circulating Tfh (cTfh; memory CD4+CXCR5+)/B-cell (CD19+) co-culture assays revealed that CNI considerably inhibited cTfh-mediated B-cell activation and IgG antibody secretion through the suppression of IL-21 and IL-2. Both IL-21 and CD40L up-regulated IL-2 receptors (CD25) on B cells, and anti-CD25 antibody induced apoptosis of activated B cells, resulting in the inhibition of IgG production. The frequency of cTfh-expressed CD40L and PD-1 was elevated in patients with de novo DSA 1 year after transplantation. The degree of inhibition by CNI was dependent on Staphylococcal enterotoxin B-induced CD40L+PD-1+ cTfh up-regulation level. Our data demonstrate that CD40L+PD-1+cTfh could be a marker to implicate individual difference in CNI sensitivity for Tfh-mediated B-cell activation in kidney transplantation.

Euglena extract suppresses adipocyte-differentiation in human adipose-derived stem cells.

Euglena gracilis Z (Euglena) is a unicellular, photosynthesizing, microscopic green alga. It contains several nutrients such as vitamins, minerals, and unsaturated fatty acids. In this study, to verify the potential role of Euglena consumption on human health and obesity, we evaluated the effect of Euglena on human adipose-derived stem cells. We prepared a Euglena extract and evaluated its effect on cell growth and lipid accumulation, and found that cell growth was promoted by the addition of the Euglena extract. Interestingly, intracellular lipid accumulation was inhibited in a concentration-dependent manner. Quantitative real-time PCR analysis and western blotting analysis indicated that the Euglena extract suppressed adipocyte differentiation by inhibiting the gene expression of the master regulators peroxisome proliferator-activated receptor-γ (PPARγ) and one of three CCAAT-enhancer-binding proteins (C/EBPα). Further Oil Red O staining experiments indicated that the Euglena extract inhibited the early stage of adipocyte-differentiation. Consistent with these results, we observed that down-regulation of gene expression was involved in the early stage of adipogenesis represented by the sterol regulatory element binding protein 1 c (SREBP1c), two of three CCAAT-enhancer-binding proteins (C/EBPß, C/EBPδ), and the cAMP regulatory element-binding protein (CREB). Taken together, these data suggest that Euglena extract is a promising candidate for the development of a new therapeutic treatment for obesity.

Association between characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab for diabetic macular edema.

PURPOSE: To investigate the association between the characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab treatment for diabetic macular edema (DME) at 3 months from the initial injection. METHODS: We retrospectively reviewed 66 eyes of 61 patients with center-involved DME who received three consecutive ranibizumab injections and following as-needed administrations. We evaluated the relationship between visual improvement at 3 months and the preoperative optical coherence tomography (OCT) parameters including hyperreflective foci, heterogeneous OCT reflectivity, mean levels of OCT reflectivity and height of foveal cystoid spaces. RESULTS: Twenty-three eyes without preoperative hyperreflective foci in the foveal cystoid spaces had significantly greater improvement in the logarithm of the minimum angle of resolution visual acuity (logMAR VA) at 3 months than 43 eyes with foci (P = 0.006). That was similar to the greater reduction in CSF thickness in eyes without lesions after treatment at the same time point (P < 0.001). VA improvement at 3 months was not associated with the height (R = 0.215, P = 0.083) or the reflectivity levels (R = -0.079, P = 0.538) of foveal cystoid spaces. There were no differences in VA changes between eyes with and without heterogeneous reflectivity in foveal cystoid spaces (P = 0.297). Multivariate analyses showed that logMAR VA and the absence of hyperreflective foci in foveal cystoid spaces were associated with VA improvement at 3 months. CONCLUSION: Hyperreflective foci in foveal cystoid spaces at baseline predict poorer short-term responsiveness to ranibizumab injections for DME.

EVALUATION OF MACULAR ISCHEMIA IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

PURPOSE: To quantitatively assess macular perfusion status using optical coherence tomography angiography in eyes with aflibercept-treated central retinal vein occlusion and resolved macular edema and to investigate the impact of macular morphology and perfusion status on visual function. METHODS: This prospective consecutive case series included 23 patients with central retinal vein occlusion. All patients received intravitreal aflibercept injections before analysis. Visual acuity, macular sensitivity, and the macular nonperfusion area (NPA) were evaluated in eyes without macular edema. The macular NPA was evaluated by optical coherence tomography angiography using 3 mm × 3 mm images of the macula. Foveal ellipsoid zone disruption was also analyzed. RESULTS: The superficial macular NPA measured 4.15 mm ± 0.71 mm (95% confidence interval 3.85-4.46), and the deep macular NPA measured 4.23 mm ± 0.97 mm (95% confidence interval 3.82-4.56). The logarithm of the minimum angle of resolution visual acuity was significantly associated with foveal ellipsoid zone disruption (P = 0.001), the superficial macular NPA (P = 0.015), and the deep macular NPA (P = 0.018). Macular sensitivity correlated negatively with logarithm of the minimum angle of resolution visual acuity (P = 0.007), the superficial macular NPA (P = 0.029), and the deep macular NPA (P = 0.040), but not with the foveal ellipsoid zone disruption (P = 0.435). CONCLUSION: Optical coherence tomography angiography is a novel technique that enables segmented evaluation of the macular perfusion status in eyes with central retinal vein occlusion and provides visual prognostic information. Enlargement of the macular NPA in the superficial and deep layers was significantly correlated with impaired visual acuity and with decreased macular sensitivity in patients with aflibercept-treated central retinal vein occlusion and resolved macular edema.