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Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that β-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that β-cell-specific p62 deficiency does not cause any apparent impairment in glucose metabolism. In the present study, we investigated the roles of p62 in β cells under autophagy-deficient conditions, by simultaneously inactivating both Atg7 and p62 in a β-cell specific manner. Whereas p62 accumulation was substantially reduced in the islets of Atg7 and p62 double-deficient mice, glucose tolerance and insulin secretion were comparable to Atg7 single-deficient mice. Taken together, these findings suggest that the p62 accumulation appears to have little effect on β-cell function under conditions of autophagy inhibition.

Autophagy is known to play a pivotal role in β-cell function. While the lifelong inhibition of autophagy through Atg7 deletion in β cells has been demonstrated to lead to impaired glucose tolerance together with β-cell dysfunction, the temporal association between autophagy inhibition and β-cell dysfunction remains unclear. To address such questions, inducible β-cell-specific Atg7-knockout (iβAtg7

As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, possible methods to efficiently generate surrogate β cells have attracted a lot of efforts. To date, insulin-producing cells have been generated from various differentiated cell types in the pancreas, such as acinar cells and α cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate β cells can be efficiently generated for establishing future regenerative therapies for diabetes. In this study, we demonstrated that the exogenous expression of PDX1 activated STAT3 in α cells in vitro, and STAT3-null PDX1-expressing α cells in vivo resulted in efficient induction of α-to-β reprogramming, accompanied by the emergence of α-cell-derived insulin-producing cells with silenced glucagon expression. Whereas β-cell ablation by alloxan administration significantly increased the number of α-cell-derived insulin-producing cells by PDX1, STAT3 suppression resulted in no further increase in β-cell neogenesis after β-cell ablation. Thus, STAT3 modulation and β-cell ablation nonadditively enhance α-to-β reprogramming induced by PDX1, which may lead to the establishment of cell therapies for curing diabetes.

Background: Estimating the nutritional content of food is essential for self-management in people with type 2 diabetes mellitus, but it is a difficult skill to learn. The aim of this study was to investigate how diabetes management was impacted by the ability of patients to search for items they ate from a database of 26,300 different foods, and to visualize nutritional intake using the Japanese mobile application (app) "Calomeal." Methods: This was a single-arm, single-center, pilot study. Eighteen outpatients with type 2 diabetes mellitus used the "Calomeal" app for 3 months. The primary endpoint was change in hemoglobin A1c (HbA1c). Secondary endpoints were changes in body weight (BW), lipid parameters, and quality of life scores. Results: The baseline characteristics of the study subjects were as follows: age: 53.4 ± 7.8 years; male/female ratio: 11/7; HbA1c: 7.9 (7.58 - 8.23)%; and body mass index (BMI): 25.17 (21.63 - 28.59) kg/m 2 . Significant reductions in HbA1c and BMI were observed over 3 months (HbA1c: 7.9 (7.58 - 8.23)% to 7.6 (7.3 - 8.23)%, P = 0.0410; BMI: 25.17 (21.63 - 28.59) to 24.54 (21.57 - 27.81) kg/m 2 , P = 0.0057). Reductions in HbA1c and BMI both correlated with decreased carbohydrate intake estimated by the mobile app. Conclusions: Japanese patients who used their smartphones to visualize their nutritional intake using the "Calomeal" app demonstrated improved short-term glycemic control and BMI. Although the validity of the results should be tested in future randomized controlled trials, this approach may be a clinical option for improving self-management in Japanese patients with type 2 diabetes mellitus. J Clin Med Res. 2021;13(8):425-433 doi: https://doi.org/10.14740/jocmr4558

Aims/Introduction In Japan, an insulin pump with predictive low‐glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. Materials and Methods We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of “post‐suspend hyperglycemia” with the 640G device. Results After changing to the 640G device, the percentage of time in hypoglycemia (glucose 180 mg/dL) significantly increased from 25.53% (15.78–44.14%) to 32.9% (24.71–45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2–53.75%), but it was significantly lower, 2.78% (0–21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20–61.66%; P = 0.0063). Conclusions Predictive low‐glucose management is an effective tool for reducing hypoglycemia, but possibly elicits “post‐suspend hyperglycemia.” This information is useful for achieving better blood glucose control in the patients treated with PLGM., An insulin pump with predictive low‐glucose management was launched in 2018 in Japan. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. Predictive low‐glucose management is an effective tool for reducing hypoglycemia, but possibly elicits “post‐suspend hyperglycemia.”

While pancreatic beta cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where beta cells emerge from and which transcripts define newborn beta cells. We therefore investigated characteristics of newborn beta cells extracted by a time-resolved reporter system.We established a mouse model, 'Ins1-GFP; Timer', which provides spatial information during beta cell neogenesis with high temporal resolution. Single-cell RNA-sequencing (scRNA-seq) was performed on mouse beta cells sorted by fluorescent reporter to uncover transcriptomic profiles of newborn beta cells. scRNA-seq of human embryonic stem cell (hESC)-derived beta-like cells was also performed to compare newborn beta cell features between mouse and human.Fluorescence imaging of Ins1-GFP; Timer mouse pancreas successfully dissected newly generated beta cells as green fluorescence-dominant cells. This reporter system revealed that, as expected, some newborn beta cells arise close to the ducts (βThe combination of time-resolved histological imaging with single-cell transcriptional mapping demonstrated novel features of spatial and transcriptional heterogeneity in beta cell neogenesis, which will lead to a better understanding of beta cell differentiation for future cell therapy.Raw and processed single-cell RNA-sequencing data for this study has been deposited in the Gene Expression Omnibus under accession number GSE155742.

While pancreatic β cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where β cells emerge and which transcripts define newborn β cells. Here, we used a mouse model “Ins1-GFP;Timer” that provides spatial information during β-cell neogenesis with high temporal resolution. Fluorescent imaging demonstrated that, as expected, some newborn β cells arise close to the ducts; unexpectedly, all the others arise away from the ducts and adjacent to blood vessels. Single-cell RNA-sequencing (scRNA-seq) demonstrated five distinct populations of newborn β cells, confirming the spatial heterogeneity of β-cell neogenesis, and integration analysis with scRNA-seq of hESC-derived β-like cells uncovered transcriptional similarity with the data in mouse β cells. Thus, the combination of time-resolved histological imaging with single-cell transcriptional mapping demonstrated novel features of spatial and transcriptional heterogeneity in β-cell neogenesis, which will lead to a better understanding of β-cell differentiation for future cell therapy.

Background: The estimation of nutrient content is difficult, but important for self-management of people with type 2 diabetes mellitus (T2DM). In Japan, food-log app has not been penetrated as a treatment tool yet. That could be because Japanese food is diverse and consists of various ingredients. In this study, we investigated the efficacy of app “Calomeal” that enables the patients to search for what they eat among the database of 26300 kinds of foods and to visualize the nutrients using smartphone. Method: We recruited 20 people with T2DM in Juntendo University. They used this app for 3 months on the regular treatment. The blood and urine exams were performed monthly. At the beginning and the end of the study, the estimation of food was also assessed by the dietitian and the questionnaires about QOL (DTSQ/PAID) were performed. Results: 2 were dropped out. 18 participants were 52.3±9.2 y.o., male/female 12/8, BMI 25.8±4.7 kg/m2, and HbA1c 8.1±0.4%. At the end of study, significant reduction was observed in HbA1c and BMI (7.92±0.4 to 7.75±0.5%[p=0.0410], 25.69±5.0 to 25.10±4.8 kg/m2 [p=0.0057]). Reduction of HbA1c and BMI were both correlated to the reduction of carbohydrate (r=0.5018 [p=0.0338], r =0.5542 [p=0.0170]). High correlation was also observed between the reduction of carbohydrate and calorie (r=0.8167 [p Conclusion: Visualizing nutrients via Calomeal improved glycemic control and BMI by reducing over intake. It is of note that in some Japanese people, the adjusting nutrient intake by raising the calorie may contribute to their QOL. Disclosure A. Tsunemi: None. J. Sato: Research Support; Self; Sanofi. Speaker’s Bureau; Self; Daiichi Sankyo, Medtronic, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. M. Enomoto: None. Y. Iwagaki: None. S. Sugimoto: None. Y. Someya: None. M. Kiya: None. E. Matsuhashi: None. Y. Wakabayashi: None. T. Funayama: None. T. Uchida: None. T. Miyatsuka: None. K. Azuma: None. T. Shimizu: None. H. Satoh: None. A. Kanazawa: Speaker’s Bureau; Self; Novartis Pharma K.K., Sanofi, Takeda Pharmaceutical Company Limited. H. Watada: Advisory Panel; Self; Abbott, Ajinomoto, Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Fuji Film, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Yakult. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

Acetaldehyde dehydrogenase 2 (ALDH2) is an enzyme involved in redox homeostasis as well as the detoxification process in alcohol metabolism. Nearly 8% of the world’s population have an inactivating mutation in the ALDH2 gene. However, the expression patterns and specific functions of ALDH2 in skeletal muscles are still unclear. Herein, we report that ALDH2 is expressed in skeletal muscle and is localized to the mitochondrial fraction. Oxidative muscles had a higher amount of ALDH2 protein than glycolytic muscles. We next comprehensively investigated whether ALDH2 knockout in mice induces mitochondrial adaptations in gastrocnemius muscle (for example, content, enzymatic activity, respiratory function, supercomplex formation, and functional networking). We found that ALDH2 deficiency resulted in partial mitochondrial dysfunction in gastrocnemius muscle because it increased mitochondrial reactive oxygen species (ROS) emission (2′,7′-dichlorofluorescein and MitoSOX oxidation rate during respiration) and the frequency of regional mitochondrial depolarization. Moreover, we determined whether ALDH2 deficiency and the related mitochondrial dysfunction trigger mitochondrial stress and quality control responses in gastrocnemius muscle (for example, mitophagy markers, dynamics, and the unfolded protein response). We found that ALDH2 deficiency upregulated the mitochondrial serine protease Omi/HtrA2 (a marker of the activation of a branch of the mitochondrial unfolded protein response). In summary, ALDH2 deficiency leads to greater mitochondrial ROS production, but homeostasis can be maintained via an appropriate stress response.

Mechanical unloading impairs cytosolic calcium (Ca2+) homeostasis in skeletal muscles. In this study, we investigated whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) itself or one of the regulators of the Ca2+SERCA pump, sarcolipin (SLN), is altered to deregulate Ca2+homeostasis in cast immobilized, atrophied muscles. Hindlimb muscles of 8-wk-old male C57BL/6J mice were subjected to bilateral cast immobilization for 2 wk. Two-week-cast immobilization induced both body weight and skeletal muscle loss. Highly phosphorylated Ca2+/calmodulin-dependent protein kinase II in the atrophied muscles suggested that cytosolic Ca2+concentration was elevated. Extremely high expression levels of SLN mRNA and protein were observed in the atrophied muscles. Upregulation of SLN at the transcriptional level was supported by low RCAN1 expression, which is a negative regulator of SLN. We treated C2C12cells with dexamethasone to mimic muscle atrophy in vitro and showed a direct relationship between high SLN mRNA expression and low Ca2+uptake by sarcoplasmic reticulum. Since SLN reportedly plays a role in nonshivering thermogenesis, we performed a cold tolerance test of the whole body. As a result, we found that mice with cast immobilization showed high cold tolerance, suggesting that cast immobilization promoted whole body thermogenesis. Although the activity level was decreased during cast immobilization without change in food intake, adipose tissue weights also decreased significantly after cast immobilization. Concomitantly, we conclude that cast immobilization of hindlimb increased thermogenesis in C57Bl/6J mice, probably via high expression of SLN.

As diabetes mellitus results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, the generation of surrogate β cells has attracted a lot of attention for the cure of diabetes. To date, insulin-producing cells have been generated from differentiated cell types in the pancreas, such as acinar cells and α cells, by inducing the exogenous expression of pancreas-specific transcription factors. However, it still remains unclear as to how surrogate β cells can be efficiently generated toward establishing future regenerative therapies for diabetes. STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, and we have reported that the activation of STAT3 signaling is required for acinar-to-ductal transition (Miyatsuka et al. Genes Dev. 2006), whereas the suppression of STAT3 signaling efficiently promotes acinar-to-β reprogramming (Miura M. et al. EBioMedicine. 2018). Therefore, we hypothesized that regulating STAT3 signaling may control the efficiency of α-to-β reprogramming. To address this, we generated transgenic mice that exogenously express Pdx1, Mafa and Ngn3 specifically in α cells, and deleted Stat3 in a tamoxifen inducible manner (Stat3KO; Gcg-CreERT2; Pdx1;Ngn3;Mafa mice: αStat3KO;PNM mice). Immunofluorescent imaging demonstrated that Stat3 deletion significantly increased the number of α-cell-derived insulin-producing cells in αStat3KO;PNM mice, compared with control mice (28.2±2.7 vs. 8.6±3.1%, p Disclosure Y. Wakabayashi: None. T. Miyatsuka: None. L. Suzuki: None. M. Himuro: None. T. Katahira: None. M. Miura: None. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

Background and Objective: Sensor-augmented pumps (SAP) that suspend insulin when glucose is low or predicted to go low within the next 30 minutes (The MiniMed™ 640G insulin pump) have been approved in Japan from March 2018. The system, Smart GuardTM technology, would automatically resume insulin delivery when glucose levels recover. The aim of this observational study is to evaluate the effectiveness of Smart GuardTM technology, which may offer the opportunity to reduce hypoglycemia for the patients with type 1 diabetes. The primary outcome is the change of the percentage of time in hypoglycemia (%Time in hypoglycemia Method: In Juntendo University Hospital, among 49 patients with the MiniMed™ 620G (SAP without Smart GuardTM technology), we analyzed the data of 17 patients (male/female: 4/13, age: 51.2±17.6 years old) who changed from 620G to 640G. Results: After 2 months use of 640G, %TIHypo decreased from 2.97[1.15-6.27]% to 1.48[0.06-2.81]%, and HbA1c (%) increased from 7.00[6.45-7.65]% to 7.25[6.73-8.28]%. %TIHyper (%Time in hyperglycemia>180 mg/dl) increased from 26.06[19.74-37.28]% to 31.80[18.65-46.31]%. None of them were statistically significant. Conclusions: In the real-world data, the Smart GuardTM technology of 640G could have decreased the time in hypoglycemia. In many cases, sensor glucose after suspending basal insulin tend to be higher, therefore, patients might have to increase the insulin dose after suspending. We need to study on a larger sample of patients and with a more prolonged follow-up. Disclosure A. Tsunemi: None. J. Sato: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited. M. Kurita: None. Y. Wakabayashi: None. N. Waseda: None. M. Koshibu: None. M. Shinohara: None. A. Ozaki: None. H. Nakamura: None. N. Hirano: None. F. Ikeda: None. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. Although βcell mass is increased during pregnancy and starts to return toward its original level shortly after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust down-regulation of cell cycle-related genes 1 day after parturition, and the biphasic up-regulation of serotonin metabolism-related genes during pregnancy and at postpartum day 7. Serotonin synthesis was activated during lactation in human as well as in mice. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis. Funding Statement: This work was supported by research grant for Cross-disciplinary Collaboration, Juntendo University 2017 (29-35). Declaration of Interests: The authors stated: "There is no conflict of interest on this study." Ethics Approval Statement: The study design was approved by the ethics committee of the Hirosaki University School of Medicine (approval number 2014-269), and the study conforms to the provision of the Declaration of Helsinki.

金沢大学附属病院眼科, Purpose: To describe fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (SD-OCT) findings of leopard spots in nanophthalmic uveal effusion syndrome. Methods: A 34-year-old man with retinal detachment associated with nanophthalmic uveal effusion syndrome in the right eye underwent sclerotomy three times. After the final surgery, the subretinal fluid resolved gradually. Then, SD-OCT examination, FAF photography, fluorescein angiography (FA), and indocyanine green angiography (ICGA) were performed simultaneously with the spectralis Heidelberg retina angiograph + OCT system. Results: SD-OCT revealed focal thickening of the retinal pigment epithelium (RPE) layer at the same locations as leopard spots, which appeared hypofluorescent on FA and ICGA. These spots showed hyperautofluorescence on FAF imaging. Six months later, focal thickening of the RPE layer became smaller on OCT and hyperautofluorescence was attenuated on FAF imaging. Conclusions: Simultaneous imaging of the fundus with multiple modalities including OCT, FAF, FA, and ICGA indicates that leopard spots in the fundus of uveal effusion syndrome may show hyperautofluorescence and correspond to focal thickening of the RPE layer by SD-OCT. This imaging method may help elucidate the pathology of various fundus lesions in vivo. © 2010 Springer-Verlag.

Purpose: To report clinical findings of three patients with unilateral peculiar choroidal excavation in the macula detected by spectral-domain (SD) optical coherence tomography (OCT). Methods: Three cases with unilateral choroidal excavation in the macula detected by SD OCT. Fluorescein angiography (FA), indocyanine green angiography (IA), ultrasonography, visual field tests and multifocal electroretinography (mfERG) were performed. Results: Although all three patients complained of metamorphopsia, visual acuity and central visual field were normal in the affected eyes. SD OCT demonstrated choroidal excavation in the macula despite a normal foveal contour along the inner retinal surface. The excavation involved the outer retinal layers up to the external limiting membrane in cases 1 and 2, while only the retinal pigment epithelium was involved in case 3. The excavation corresponded to foveal pigment mottling in cases 1 and 2 and to a parafoveal yellowish fusiform lesion in case 3. The lesions appeared hypoautofluorescent and unremarkable in FA except for circumferential hyperfluorescence in case 3 and hypofluorescent in IA. B-scan ultrasonography was unremarkable. MfERG in cases 1 and 2 was normal. Conclusions: SD OCT demonstrated two types of choroidal excavation in the macula. More case accumulation and a longer follow-up will elucidate the pathogenesis and prognosis of the lesions.

To examine the effects of multiple intraocular pressure (IOP) measurements on the correlation of response to glaucoma medication between fellow eyes.Latanoprost was applied to the first eye and then to both eyes of 16 patients with either primary open-angle glaucoma or ocular hypertension. IOP measurements were performed twice on different days for each of three periods: at baseline, during treatment of the first eye only and for both eyes. IOP decreases in the first and second eyes were evaluated with ∆IOP 1 (=IOP at baseline - IOP after treatment) and ∆IOP 2 (=∆IOP 1 - IOP fluctuation of the contralateral eye). The correlation of IOP decreases between the fellow eyes was analyzed by linear regression analysis using the Pearson correlation coefficient, r.No significant correlations of ∆IOP1 between fellow eyes were found regardless of the number of IOP measurements. ∆IOP2 was significantly correlated between fellow eyes using two post-treatment IOP measurements, but not with a single post-treatment IOP.Using multiple post-treatment IOP measurements may improve the prediction of a fellow eye's response to glaucoma medication in one-eye trials.