A randomized Phase I study of the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 456906, a dual glucagon receptor/glucagon-like peptide-1 receptor agonist, in healthy Japanese men with overweight/obesity.

AIM: To report a Phase I study of subcutaneous glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist BI 456906 versus placebo in healthy Japanese men with overweight/obesity. MATERIALS AND METHODS: We investigated multiple rising doses of BI 456906 escalated over 16 weeks (maximum doses: 1.8 mg once weekly [dose group {DG} 1], 4.8 mg once weekly [DG 2] and 2.4 mg twice weekly [DG 3]) in Japanese men with a body mass index of 23 to 40 kg/m2 . RESULTS: Thirty-six participants were treated (n = 9 per DG and placebo). Overall, 10 participants (37.0%) treated with BI 456906 withdrew from dose escalation due to adverse events (amylase increase, n = 1; decreased appetite, n = 9), and the proportion of participants was higher in DG 2 (n = 6, 66.7%) versus DGs 1 and 3 (both n = 2, 22.2%). No participants receiving placebo withdrew from dose escalation. BI 456906 exposure increased with dose and dose escalation in each DG. Treatment with BI 456906 decreased placebo-corrected bodyweight after 16 weeks (placebo +1.06%): DG 1, -5.57%; DG 2, -12.37%; DG 3, -9.62%. Paracetamol absorption decreased in Week 1 for DGs 2 and 3, indicating transient delayed gastric emptying. BI 456906 reduced plasma alanine and glucagon levels, indicating indirect target engagement at GCGRs and GLP-1Rs. Drug-related adverse events were reported for all participants receiving BI 456906 and four receiving placebo, the most frequent being decreased appetite (n = 24, 66.7%). CONCLUSIONS: BI 456906 showed no unexpected tolerability concerns and it reduced placebo-corrected bodyweight by up to 12.37% in Japanese men with overweight/obesity after 16 weeks of treatment.

Prediction of Oral Drug Absorption in Rats from In Vitro Data.

PURPOSE: In 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. METHOD: The 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. RESULTS: The 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. CONCLUSION: The 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.

A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors.

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).

ONE-YEAR OUTCOMES OF METAMORPHOPSIA AND RETINAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To examine 1-year outcomes of metamorphopsia and tangential retinal displacement after epiretinal membrane surgery and identify predictors for metamorphopsia score at 1 year and its improvement from baseline. METHODS: M-CHARTS were used to measure metamorphopsia. Distances between the intersections of two sets of retinal vessels were measured with infrared or autofluorescence images. Predictors for metamorphopsia scores at 1 year after surgery and their differences from baseline were identified with multivariate regression analysis. RESULTS: Ninety-two eyes of 90 consecutive patients were included. The vertical and horizontal distances continued expanding for 1 year ( P < 0.001). Both vertical and horizontal metamorphopsia scores improved 3 months after surgery ( P = 0.025 and P < 0.001, respectively), and horizontal scores continued improving for a year. Horizontal metamorphopsia scores correlated with retinal displacement more strongly than vertical scores. Higher metamorphopsia score at baseline is predictive for that at 1 year. Older age and being male are predictive for less improvement of the score at 1 year from baseline. CONCLUSION: Metamorphopsia correlates with tangential retinal displacement at 1 year after epiretinal membrane surgery. Horizontal metamorphopsia scores keep improving until 1 year postoperatively. Being male and older age are both independent predictors for poor improvement of metamorphopsia after epiretinal membrane surgery.

Assessment of the deformation of the outer nuclear layer in the Epiretinal membrane using spectral-domain optical coherence tomography.

BACKGROUND: We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia. METHODS: Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated. RESULTS: ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 µm and 84.1 ± 12.9 µm, respectively; P < 0.001). In ERM patients, the MV score was 0.53 ± 0.50, the MH score was 0.71 ± 0.61, and the distance from the RPE line to the ONL-B was 153.5 ± 13.5 µm. The axis of the ONL-B in normal controls and ERM patients was - 6.25 ± 21.8 and - 1.28 ± 29.1, respectively, which indicates that the ONL is horizontally long in both normal individuals and ERM patients. The circularity and area ratio were significantly smaller in ERM patients than in normal controls. In all ERM patients, MH/MV had a significant correlation with axis (r = - 0.29, p = 0.034), circularity (r = - 0.28, p = 0.044), and area ratio (r = - 0.47, p = 0.001). Moreover, we found that the correlation was more significant if the subjects had an axis of the ONL within ±10 degrees (n = 16); the correlations of MH/MV with axis (r = - 0.29, p = 0.034), circularity (r = - 0.53, p = 0.021), and area ratio were more significant (r = - 0.78, P < 0.0001). CONCLUSION: The ONL is horizontally long in normal individuals and ERM patients. The direction of metamorphopsia is correlated with the direction of ONL deformation.

METAMORPHOPSIA AND TANGENTIAL RETINAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To determine whether the degree of metamorphopsia significantly correlated with the distance of the tangenital retinal displacement after epiretinal membrane surgery. METHODS: The M-CHARTS were used to measure the vertical metamorphopsia score and the horizontal score. The distances between the intersections of two sets of retinal vessels situated vertically or horizontally were measured in the near-infrared Spectralis images. RESULTS: Fifty eyes of 50 patients (22 men; age, 69.5 ± 7.8 years) were retrospectively studied. The vertical and horizontal metamorphopsia scores significantly improved at 1 month after the surgery, and the vertical and horizontal retinal distances increased. The baseline horizontal and vertical metamorphopsia scores significantly correlated with the ratio of the pre- and postoperative vertical and horizontal retinal displacements, respectively (P = 0.038 and P = 0.015 at 1 week; P = 0.036 and P = 0.036 at 1 month). The postoperative horizontal metamorphopsia score at 1 month and the vertical metamorphopsia score at 3 months significantly correlated with the vertical displacement at 1 month (P = 0.034) and the horizontal displacement at 3 months (P = 0.001), respectively. CONCLUSION: The degree of metamorphopsia significantly correlated with the tangential retinal displacement. Dislocated Müller cells may stimulate the photoreceptors located away from original positions, which consequently results in the sensation of metamorphopsia in patients with an epiretinal membrane.

RETINAL PIGMENT EPITHELIUM UNDULATIONS IN ACUTE STAGE OF VOGT-KOYANAGI-HARADA DISEASE: Biomarker for Functional Outcomes After High-Dose Steroid Therapy.

PURPOSE: To determine the clinical significance of retinal pigment epithelium (RPE) undulations in the acute stage of Vogt-Koyanagi-Harada disease. METHODS: Retinal pigment epithelium undulations were detected and classified into 3 grades: Grade 1, slight; Grade 2, moderate; and Grade 3, severe undulations, in the enhanced depth imaging optical coherence tomographic images. The relationship between the clinical characteristics and the presence of RPE undulations was investigated. RESULTS: Among the 61 eyes of 31 patients with Vogt-Koyanagi-Harada disease, 40 eyes had some degree of RPE undulations (Grade 1 = 12, Grade 2 = 15, and Grade 3 = 13). The patients with RPE undulations in both eyes were significantly older at the onset (P = 0.0002). The eyes with RPE undulations were more likely to develop posterior recurrences (P = 0.032) and have worse vision at 12 months (P = 0.043). Multiple regression analysis revealed that RPE undulations were an independent predictor of posterior recurrences (P = 0.009) and poor visual outcomes (P = 0.035). CONCLUSION: Retinal pigment epithelium undulations detected by enhanced depth imaging optical coherence tomographic are relatively frequent occurrences at the acute stage of Vogt-Koyanagi-Harada, and their presence is a predictor of posterior recurrences and poor visual outcomes after high-dose steroid therapy.

Preclinical metabolism and disposition of luseogliflozin, a novel antihyperglycemic agent.

1. We investigated the metabolism and disposition of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in rats and dogs, as well as in vitro metabolism in rats, dogs and humans. In addition, we studied its localization in the rat kidney. 2. [14C]Luseogliflozin was rapidly and well absorbed (>86% of the dose) after oral administration to rats and dogs. The drug-derived radioactivity was mainly excreted via the feces in both species. 3. The predominant radioactivity component in the excreta was associated with the metabolites, with only a minor fraction of unchanged luseogliflozin. The major metabolites were two glucuronides (M8 and M16) in the rats, and the O-deethylated form (M2) and other oxidative metabolites (M3 and M17) in the dogs. 4. The in vitro metabolism in dog and human hepatocytes was significantly slower than that in the rat hepatocytes. The biotransformation in animal hepatocytes was similar to that observed in vivo. Incubation with human hepatocytes resulted in the formation of metabolites, including M2, M3, M8 and M17, via multiple metabolic pathways. 5. [14C]Luseogliflozin was well-distributed to its target organ, the kidney, and was found to be localized in the renal cortex, which shows SGLT2 expression. This characteristic distribution was inhibited by preinjection of phlorizin, an SGLT inhibitor, suggesting that the renal radioactivity was associated with SGLT2.

Catalytic amide allylation of α-ketoesters: extremely high enantioselective synthesis of ester functionalised α-methylene-γ-butyrolactones.

This communication reports a significant breakthrough on the novel catalytic amide allylation to the acyclic α-ketoester systems, achieving satisfactorily high yields and extremely high levels of the asymmetric induction to allow for highly enantioselective synthesis of ester functionalised α-methylene-γ-butyrolactones.

Stage-specific quercetin sulfation in the gut of Mythimna separata larvae (Lepidoptera: Noctuidae).

The metabolism of quercetin was investigated in Mythimna separata larvae. Quercetin 4'-O-sulfate was mainly identified in the frass when 6th instar larvae were fed artificial diets containing 1% quercetin. In the case of the 3rd instar larvae, a larger amount of quercetin was detected in the frass. M. separata larvae had different metabolic strategies for quercetin at different developmental stages.

Photoreceptor inner and outer segment layer thickness in multiple evanescent white dot syndrome.

PURPOSE: To evaluate the photoreceptor inner and outer segment layer thickness in eyes with MEWDS. DESIGN: Prospective, non-comparative, observational case series. The follow-up duration was 4 months. METHODS: Four women were diagnosed with unilateral MEWDS. The ages of the patients were 25, 24, 35, and 40 years. The retinal microstructure was assessed by spectral-domain optical coherence tomography (SD-OCT). The thickness of the photoreceptor inner (IS) and outer (OS) segments and sum of them (IS + OS) at the fovea were analyzed. RESULTS: The visual acuity was reduced in three of four eyes at the acute phase. SD-OCT showed that the border of IS and OS (IS/OS) line and the cone outer segment tips (COST) line in the macula area were not detected in all four eyes. The IS + OS thickness was 50.3 ± 5.6 µm and that of the healthy fellow eyes was 73.5 ± 7.0 µm (n = 4 eyes). The thickness of the IS was 27.8 ± 2.6 µm and that of the OS was 45.8 ± 7.3 µm. In all eyes, there was a spontaneous improvement of the visual acuity. SD-OCT showed a recovery of only the IS/OS line in the macular area, but the COST line was not visible in three cases. The mean IS + OS thickness increased to 56.0 ± 7.9 µm (n = 4), IS = 26.0 ± 2.0 µm (n = 3), and OS = 30.1 ± 8.7 µm (n = 3) in the early recovery phase, and to 64.8 ± 9.3 µm (n = 4), IS = 28.5 ± 1.7 µm (n = 4), and OS = 36.3 ± 7.9 µm (n = 4) in the late recovery phase. The mean inner and outer segment thickness remained unchanged in the fellow eyes. CONCLUSION: Eyes with MEWDS have changes in the photoreceptor microstructures. The change in the IS + OS thickness during the natural recovery course might be due to an increase in the OS length.

Aniseikonia and retinal morphological changes in eyes undergoing macular hole surgery.

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.

Predictors for metamorphopsia in eyes undergoing macular hole surgery.

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.

Current situation and clinical burden of pediatricians for children with eating disorders during the COVID-19 pandemic.

During the COVID-19 pandemic, the incidence of eating disorders (ED) has increased not only in Japan but also worldwide. This online survey for pediatricians showed that caregivers tend to visit specific pediatric institutions or child psychiatry departments when children under junior high school age develop eating disorders. There are few pediatric institutions regarding treatment acceptance for children with ED. Of the 34 respondents, 16 (47.1%) answered that the number of visits for children with eating disorders had "stayed the same", one answered it had "decreased" and 17 (50.0%) answered it had "increased" or "increased very much". In addition, 28 of the 34 respondents (82.3%) experienced difficulties with psychotherapy for children with ED. For treating children with ED, pediatricians usually conducted physical examination and have some clinical burden. ED are increasing in the COVID-19 pandemic. Because children with severe ED need to be hospitalized, child and adolescent psychiatric wards are overcrowded and some children with other mental disorders can't be admitted.

Influence of skin thickness on the in vitro permeabilities of drugs through Sprague-Dawley rat or Yucatan micropig skin.

The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 model drugs with different physicochemical properties (nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP)) through Sprague-Dawley rat (rat) or Yucatan micropig (YMP) skin. Intact, dermis-split, stratum corneum-stripped or stratum corneum-stripped and dermis-split rat or YMP skin (rat skin thickness: approximately 0.4, 0.9 or 1.2 mm; YMP skin thickness: approximately 0.4, 0.9, 1.8 or 2.8 mm) were set in Franz-type diffusion cells to determine the permeation rate, lag time and resistance ratio of the viable epidermis and dermis against whole skin (R(ved)/R(tot)) of the drugs. The YMP skin permeabilities of the drugs decreased with an increase in the skin thickness, and significant differences were observed in the permeation rates and lag times between intact and dermis-split (0.4 mm) YMP skins. The decreases in the permeabilities of the drugs through the YMP skin were larger than those through the rat skin. The influence of resistances of ISDN and FP through the dermis-split rat or YMP skin was greater at 0.9 mm skin thickness than 0.4 mm skin thickness. The R(ved)/R(tot) values for the YMP skins were relatively large for lipophilic drugs (ISDN and FP), and these ratios increased with an increase in the dermis thickness. These results suggest that in vitro skin permeation studies must be done using dermis-split (0.4 mm) skin with the thinnest dermis for predicting in vivo human percutaneous absorption rate.

Outer retinal microstructure and visual function after macular hole surgery with and without Brilliant Blue G.

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.

Retinal displacement and intraretinal structural changes after idiopathic macular hole surgery.

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.

Surgical Success Rate of Scleral Buckling Surgery and Postoperative Incidence of Cystoid Macular Edema: 10 Years of Experience at a Single Academic Hospital.

The purposes of this study were to report the surgical success rate of scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD) in a single academic hospital, analyze the incidence of cystoid macular edema (CME) after SB using optical coherence tomography (OCT), and reveal the factors associated with the development of CME. This was a retrospective observational study of patients with RRD who underwent SB from 2010 to 2020 in a single academic hospital. The anatomical success was initially achieved in 267 of 288 eyes (92.7%), and finally achieved in 288 eyes (100%). After excluding 17 eyes that underwent vitrectomy for reoperations, a total of 271 eyes of 267 patients (173 men; age, 43.5 ± 16.9 years) were retrospectively analyzed to evaluate the incidence of postoperative CME. CME occurred in 6 of 271 eyes (2.2%) within 3 months after initial surgery. Pseudophakic and aphakic eyes appeared more likely to develop CME (chi-squared test: p = 0.0078). Five of the six cases with postoperative CME were able to be medically treated. Scleral buckling surgery showed a high success rate even in the era of small-gauge vitreous surgery, and the postoperative frequency of CME after SB was low (2.2%). Previous cataract surgery may be associated with the development of postoperative CME, which is mostly medically manageable.

Inner retinal structure and visual function after idiopathic epiretinal membrane surgery with and without brilliant blue G.

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.

Choroidal thickness and intraocular pressure after 25-gauge and 23-gauge vitrectomy for idiopathic epiretinal membrane.

PURPOSE: To determine the relationship between the subfoveal choroidal thickness (SCT) and intraocular pressure (IOP) following 25-gauge (25G) and 23-gauge (23G) vitrectomy for idiopathic epiretinal membrane (ERM). STUDY DESIGN: Retrospective, consecutive, interventional case series. METHODS: Sixty-two patients undergoing 25G vitrectomy and 56 patients undergoing 23G vitrectomy for ERM participated. SCT was measured using enhanced depth imaging optical coherence tomography and IOP were measured both at baseline and postoperatively. RESULTS: In both groups, the IOPs on day one and one week after surgery were significantly lower than at baseline (P < 0.001 for both). The rates of changes of IOP were significantly greater in 23G compared to 25G on day one (P = 0.026). In 23G the SCTs on day one and one week after surgery were significantly thicker (P < 0.001) than baseline. The rates of changes in SCT between baseline and day one negatively correlated with those of IOP in 23G (r = -0.559, P < 0.001) but no correlation was observed with 25G (r = -0.129, P = 0.316). CONCLUSION: Choroidal thickness increases soon after 23G vitrectomy for ERM which is probably due to the transient hypotony, however, early SCT change does not appear in 25G vitrectomy. Twenty-five-gauge vitrectomy may have an advantage in minimizing postoperative choroidal changes.