Explore the vast range of titles available.

Purpose To investigate the correlations of thickness of three retinal layers with retinal displacement after idiopathic macular hole surgery. Study design Retrospective, consecutive, case series. Methods 42 eyes of 42 patients undergoing macular hole surgery with internal limiting membrane peeling were studied. Retinal distance was measured with near-infrared images between the optic nerve and the intersection of retinal vessels at four quadrants. Retinal thicknesses of inner retinal layer, inner nuclear layer and outer retinal layer were measured 1000 μm away from the central fovea using Spectralis. Results Retinal distances other than the nasal quadrant decreased postoperatively (p < 0.001). Retinal displacement (%) correlated significantly with the change in inner nuclear layer thickness in the temporal sector at 1, 3, and 6 months, in the superior sector at 2 weeks, 1, and 6 months, and in the inferior sector at 3 and 6 months postoperatively (r = 0.319–0.570, p < 0.001–0.040), but not in the inner or outer retinal layers. Conclusion Internal limiting membrane peeling for macular hole enhances retinal displacement toward the optic disc, whose distances correlate with the changes in inner nuclear layer thickness.

Purpose Vital dyes are frequently used to visualize the internal limiting membrane (ILM) of the neuroretina. This study evaluated and compared the microstructure of the inner retina and visual function with and without brilliant blue G (BBG) staining for ILM peeling during idiopathic epiretinal membrane (ERM) surgery. Study design Retrospective, consecutive, interventional case series. Methods Fifty-five patients (55 eyes) with ERM underwent ILM peeling without dyes (non-dye group) and 55 patients (55 eyes) underwent ILM peeling with BBG staining (BBG group). The logMAR visual acuity (VA) and ganglion cell complex (GCC) thickness were measured using optical coherence tomography at baseline and 12 months after surgery. Results LogMAR VA improved significantly in both groups at 12 months and the BBG group tended to be better than the non-dye group but with no significant difference between the groups (unpaired t -test, P = 0.490). The average GCC thickness significantly decreased in both groups; however, there was no difference in the rates of change in GCC thickness between the groups. The ratio of GCC thickness to total retinal thickness (%) was significantly higher in the BBG group in the superior quadrant at 12 months postoperatively (P = 0.010). Conclusion BBG-assisted ERM surgery resulted in better visual improvement and fewer structural changes in the inner retinal layers. BBG-assisted ILM peeling is safe both functionally and anatomically.

Even after idiopathic macular hole (MH) surgery and with successful closure of MH, aniseikonia is a common postoperative symptom. We investigated the correlation of MH diameter, retinal displacement and retinal layer thicknesses with aniseikonia in 41 eyes of 41 patients undergoing MH surgery with internal limiting membrane peeling. Aniseikonia was measured with the New Aniseikonia Test. Retinal displacement (RD%) was defined as change of retinal distance between the temporal margin of the optic papilla and the intersection of the retinal vessels. Changes of thicknesses of the inner nuclear layer (INL%) and the outer retinal layer (OR%) were calculated. Aniseikonia improved postoperatively. Preoperative aniseikonia and their improvement at 6 months correlated with MH diameters ( P  = 0.004–0.046). Improvement of aniseikonia correlated with temporal RD% ( P  = 0.002–0.012). Improvement of vertical aniseikonia correlated with INL% at 2 weeks and with the nasal OR% at 1, 3, and 6 months ( P  = < 0.001–0.028). MH diameter and age were significant predictors for improvement of aniseikonia. The greater the temporal retina displacement, and the thinner the postoperative INL and OR, the greater the improvement of aniseikonia. MH diameter and age are strong predictors for improvement of aniseikonia after MH surgery.

PurposeIn drug discovery, rats are widely used for pharmacological and toxicological studies. We previously reported that a mechanism-based oral absorption model, the gastrointestinal unified theoretical framework (GUT framework), can appropriately predict the fraction of a dose absorbed (Fa) in humans and dogs. However, there are large species differences between humans and rats. The purpose of the present study was to evaluate the predictability of the GUT framework for rat Fa.MethodThe Fa values of 20 model drugs (a total of 39 Fa data) were predicted in a bottom-up manner. Based on the literature survey, the bile acid concentration (Cbile) and the intestinal fluid volume were set to 15 mM and 4 mL/kg, respectively, five and two times higher than in humans. LogP, pKa, molecular weight, intrinsic solubility, bile micelle partition coefficients, and Caco-2 permeability were used as input data.ResultsThe Fa values were appropriately predicted for highly soluble drugs (absolute average fold error (AAFE) = 1.65, 18 Fa data) and poorly soluble drugs (AAFE = 1.57, 21 Fa data). When the species difference in Cbile was ignored, Fa was over- and under-predicted for permeability and solubility limited cases, respectively. High Cbile in rats reduces the free fraction of drug molecules available for epithelial membrane permeation while increasing the solubility of poorly soluble drugs.ConclusionThe Fa values in rats were appropriately predicted by the GUT framework. This result would be of great help for a better understanding of species differences and model-informed preclinical formulation development.

Purpose To evaluate the outer retinal microstructure and visual function after idiopathic macular hole (MH) surgery using internal limiting membrane (ILM) peeling with and without Brilliant Blue G (BBG) staining. Study design Retrospective, consecutive case series. Methods A total of 49 eyes of 47 patients were enrolled: 23 eyes of 23 patients with MH who underwent ILM peeling without dyes (control group) and 26 eyes of 26 patients who underwent BBG staining (BBG group). The lengths of defects of the photoreceptor ellipsoid zone (EZ), external limiting membrane (ELM), and interdigitation zone (IZ) were measured. Results The rate of MH closure after initial surgery was 95.6% (22/23 eyes) for the control group versus 100% (26/26 eyes) for the BBG group. In the 48 eyes with MH closure, the recovery rate of ELM deficiency and change in IZ deficiency showed no difference between the groups. The changes in EZ deficiency at 1 and 12 months were greater in the BBG group than in the control group. ( P  = 0.047 and 0.031). Visual acuity was better in the BBG group than in the control group during 12 months postoperatively ( P  < 0.001—0.038). Conclusion Eyes undergoing BBG-assisted MH surgery achieved faster recovery of the outer retinal structures and greater visual improvement than those of eyes without BBG.

Xentuzumab is an insulin‐like growth factor (IGF) ligand‐neutralizing antibody. This phase 1 trial assessed xentuzumab in Japanese patients with solid tumors. Patients aged ≥20 y old with solid tumors that were refractory or not amenable to standard therapy were enrolled. Patients received xentuzumab intravenously at a starting dose of 750 mg/wk. Dose escalation used a 3 + 3 design with dose de‐escalation. The primary endpoint was to determine the maximum tolerated dose (MTD) of xentuzumab. Safety, pharmacokinetics, pharmacodynamics, and anti‐tumor activity were also assessed. Fifteen patients received xentuzumab in the dose escalation part (750 mg/wk [n = 6]; 1000 mg/wk [n = 3]; 1400 mg/wk [n = 6]). There were no dose‐limiting toxicities at any dose; the MTD of xentuzumab was not reached. Xentuzumab 1000 mg/wk was recommended as the relevant biological dose. Six further patients received xentuzumab 1000 mg/wk in an expansion cohort. Of 21 patients, 13 (61.9%) experienced a drug‐related adverse event, most commonly fatigue (23.8%), neutropenia (19.0%), diarrhea, nausea, white blood cell count decrease, and muscle spasms (14.3% each). No relevant deviations from dose linearity of xentuzumab exposure were observed during dose escalation. Total IGF‐1 and IGF‐2 levels increased and bioactive IGF levels decreased from baseline to 24 h after the first infusion in cycle 1. Partial response was observed in 2 (9.5%) patients with desmoid‐type fibromatosis. Disease control was achieved in 6 (28.6%) patients (median duration 42.4 mo). Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti‐tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741). This phase 1 study assessed the safety and anti‐tumor activity of xentuzumab in 21 Japanese patients with solid tumors. Treatment was generally well tolerated with no significant changes in blood glucose levels and no drug‐related grade ≥3 adverse events. Two patients (9.5%) had a partial response and disease control was achieved in a total of 6 patients (28.6%); both patients with partial responses and 2 patients with stable disease had sarcomas.

Metamorphopsia is an important visual symptom of macular disease. We determined predictors for metamorphopsia investigating the relationships of macular hole (MH) diameter and retinal layer thicknesses with metamorphopsia after MH surgery. Forty-two eyes of 42 consecutive patients undergoing MH surgery were retrospectively studied. Metamorphopsia was measured with M-CHARTS. Inner nuclear layer (INL) and outer retinal layer (OR) thicknesses were measured 1000 μm away from central fovea at using Spectralis. Preoperative M-CHARTS scores correlated with MH diameters (P = 0.007–0.031) and changes of temporal OR thickness (P = 0.008–0.010). Postoperative M-CHARTS score at 3 months correlated with preoperative nasal and inferior OR thicknesses (P = 0.003 and 0.016) and with changes of superior INL at 3 and 6 months (P = 0.011 and 0.025), and score at 1 month with change of temporal OR at 6 months (P = 0.033). Postoperative improvement of M-CHARTS scores correlated with changes of temporal INL and superior OR (P = 0.026 and 0.002). Multiple regression analysis revealed that MH diameter was a significant predictor for metamorphopsia. Photoreceptor displacement and inner retinal change may generate metamorphopsia in MH undergoing surgery, however MH diameter is the most powerful predictor.

Purpose To determine the changes in retinal thickness and whether they correlate with the size of the macular hole (MH) after vitrectomy with internal limiting membrane peeling. Study design Retrospective, interventional case series Methods Consecutive patients with an MH and undergoing pars plana vitrectomy with internal limiting membrane peeling were studied. The retinal thicknesses in the inner 4 sectors as defined by the Early Treatment of Diabetic Retinopathy Study were measured using spectral-domain optical coherence tomography (SD-OCT) before and at 2 weeks and 1, 3, 6, and 12 months after the surgery. The basal and minimum diameters of the MHs were measured. The correlations between the retinal thicknesses and the size of the MH were determined. Results Thirty-three eyes of 32 consecutive patients (18 women; mean age, 64.2 ± 8.8 years) with an MH were studied. Thirteen eyes had a stage-2 MH; 12 eyes, a stage-3 MH; and 8 eyes, a stage-4 MH. The mean retinal thickness in the temporal sector was 362.8 ± 29.9 µm preoperatively, 337.9 ± 20.6 µm at 2 weeks postoperatively, and 307.6 ± 20.2 µm at 12 months postoperatively ( P < .001 for both, paired t tests). The respective mean thicknesses in the superior, inferior, and nasal sectors were 373.9 ± 34.9, 367 ± 28.7, and 385.5 ± 35.9 µm preoperatively; 361.6 ± 22.7, 359.4 ± 20.6, and 383.4 ± 29.0 µm at 2 weeks postoperatively ( P = .0087, P = .049, P = .635); and 339.4 ± 18.9, 331.6 ± 21.4, and 371.3 ± 23.2 µm at 12 months postoperatively ( P < .001, P < .001, P = .033). The changes in the retinal thickness at 2 weeks and 12 months in all 4 sectors were significantly correlated with the basal and minimum diameters of the MH. Conclusions Retinal thinning was observed soon after the MH surgery mainly in the temporal sector but also in the superior and inferior sectors. The thinning was greater in eyes with a larger MH, indicating that retinal structures dynamically change after internal limiting membrane peeling.