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AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

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Pathologic myopia is a major cause of low vision and blindness worldwide. Its social and economic burden has been demonstrated by epidemiological studies. There have been recent advances in the classification system for myopic maculopathy that enables clinicians to describe different types of lesions, including tessellated fundus, diffuse/patchy chorioretinal atrophy, macular atrophy, lacquer cracks, choroidal neovascularization (CNV), and Fuchs' spot, in a standardized format. From a therapeutic point of view, anti-vascular endothelial growth factor therapy has been established as first-line choice for myopic CNV. For myopic retinoschisis and macular holes with/without retinal detachment, pars plana vitrectomy has been generally accepted as an efficient strategy. Studies are being conducted to determine how to avoid the development of a postoperative macular hole and to improve the quality of vision after surgery. In recent years, studies have revealed preventive measures that can be taken against myopia progression, including low-dose atropine eyedrops and contact lens wearing with peripheral myopic defocusing.

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BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.

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BACKGROUND/AIMS: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). METHODS: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C). RESULTS: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively. CONCLUSION: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.

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Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Therefore, it is important to detect DR accurately during mass screening. The purpose of this study was to determine whether a small, hand-held, mydriasis-free, full-field flicker electroretinographic (ERGs) device called RETeval can be used to screen for DR. To accomplish this, we recorded full-field flicker ERGs with this device from 48 normal eyes and 118 eyes with different severities of DR in patients with diabetes mellitus (DM). This system delivered a constant flash retinal luminance by adjusting the flash luminance that compensated for changes in the pupil size. Our results showed that there were significant correlations between the severity of DR and the implicit times (P < 0.001; r = 0.55) and the amplitudes (P = 0.001; r = -0.29). When the implicit time was used for the index, the area under the receiver operating characteristic curve was 0.84 for the detection of DR, and was 0.89 for the detection of DR requiring ophthalmic treatments. These results suggest that the implicit times of the flicker ERGs recorded by the small, mydryasis-free ERG system can be used as an adjunctive tool to screen for DR.

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Diabetic retinopathy is a major cause of vision loss in Japan. Recent progress in the treatments of diabetic retinopathy includes the use of pattern scan laser photocoagulation, subthreshold micropulse laser photocoagulation, and micro incision vitreous surgery with chandelier illumination and wide-angle viewing system. The use of triamcinolone, indocyanine green or brilliant blue G, which are used to visualize the vitreous and the internal limiting membrane, respectively, has greatly facilitated vitreous surgery. As for intraocular drug therapy, antivascular endothelial growth factor agents are now available for diabetic retinopathy, useful not only for treating diabetic macular edema, but also for controlling bleeding during vitreous surgery and for temporarily suppressing the symptoms of proliferative diabetic retinopathy.

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AIM: To describe a case in which vitrectomy was required for vitreous hemorrhage and fibrovascular proliferation after laser-induced chorioretinal venous anastomosis (LCVA) for non-ischemic central retinal vein occlusion (CRVO). METHODS: Observational case report. RESULTS: A 72-year-old man complained of central scotoma in the left eye, and was diagnosed as suffering from non-ischemic CRVO. LCVA was performed in another hospital. Although favorable visual function was briefly maintained postoperatively,severe vitreous hemorrhage developed in his left eye, necessitating vitrectomy. CONCLUSION: Considering that LCVA carries a risk of serious complications, we must apply this treatment with caution, especially in ethnic groups, such as the Japanese, in whom pigmentation reacts to photocoagulation excessively.

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We evaluated the influence of posterior subtenon injection of triamcinolone acetonide on blood glucose and blood pressure in type 2 diabetes patients. This treatment, in this limited series, did not significantly increase HbA1c levels or blood pressures. But spike-like increases of fasting blood glucose were observed in some cases.

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BACKGROUND: We aim to study the circulatory parameters in the retrobulbar central retinal artery and vein in diabetic patients with and without medically treated systemic hypertension. METHODS: The study included 108 patients with diabetes that were allocated in four different groups according to the presence of diabetic retinopathy (DR) and hypertension: group 1-patients without DR and without hypertension (n = 23), group 2-patients without DR and with hypertension (n = 21), group 3-patients with nonproliferative DR and without hypertension (n = 36), group 4-patients with nonproliferative DR and with hypertension (n = 28). The circulatory parameters that were evaluated were: peak systolic blood velocity (PSV), end-diastolic blood velocity (EDV), maximum venous velocity (Vmax), minimum venous velocity (Vmin) and the Pourcelot index which were measured using color Doppler imaging. Non-parametric tests were used to test inter-group differences. Spearman's coefficient of correlation was tested between ocular perfusion pressure and the circulatory parameters in each of the patient groups. Contingency table was performed to test the relation of diabetic retinopathy and hypertension to the PSV in the central retinal artery. RESULTS: The PSV and EDV in the central retinal artery was significantly higher in group 1 (p = 0.02, p = 0.04) and group 2 (p = 0.02, p = 0.02) than in group 3. The Pourcelot index in the central retinal vein was significantly lower in group 1 than in group 4 (p = 0.02), and in group 2 than in groups 3 and 4 (p = 0.02, p < 0.01). A significant relationship was detected between the presence of hypertension, the stage of diabetic retinopathy and the PSV in the central retinal artery of our patients (chi(2) = 8.29; p = 0.04). CONCLUSION: Medically treated hypertension affects the retrobulbar circulatory parameters in the central retinal artery and vein in diabetes.

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PURPOSE: To compare eyes that received treatment with untreated fellow eyes to assess the effectiveness of injection of 20 mg of triamcinolone acetonide (TA) into the posterior sub-Tenon capsule for treatment of diabetic macular edema (DME). METHODS: Nine adult patients (mean age, 60.4 years) with DME in both eyes were followed up for 3 months after unilateral treatment. We compared central macular thickness before and after treatment with those of the untreated fellow eye. RESULTS: In 9 eyes injected with 20 mg of TA, the mean central macular thickness +/- SD was 624.8 +/- 173.7 microm before treatment. In the fellow eyes, it was 452.8 +/- 235.2 microm. There was no significant difference between the two groups (P=0.10, unpaired t-test). One month after injection, it was 434.0 +/- 120.7 microm in injected eyes (P=0.017, paired t-test) and 462.2 +/- 232.7 microm in fellow eyes (P=0.70, paired t-test), and after 3 months, the respective values were 423.1 +/- 186.3 microm (P=0.052, paired t-test) and 478.3 +/- 269.1 microm (P=0.65, paired t-test). CONCLUSION: Injection of 20 mg of TA into the posterior sub-Tenon capsule effectively reduces macular thickening due to DME, at least in the short term.

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PURPOSE: To investigate the influence of retinal photocoagulation with an indirect ophthalmoscopy contact lens on corneal endothelial cells. METHODS: Seventeen eyes of 17 patients were evaluated, and corneal endothelial cells were measured twice: just before retinal photocoagulation using an indirect ophthalmoscopy contact lens and 33.2 +/- 10.2 days after surgery. RESULTS: A statistically significant reduction was found in corneal endothelial cell numbers before versus after surgery (P = 0.0003). CONCLUSION: Our results show corneal endothelial cells to be decreased by retinal photocoagulation with an indirect ophthalmoscopy contact lens. When a patient with a low corneal endothelial cell density receives retinal photocoagulation using an indirect contact lens, it is important to be aware of the potential for further loss.

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OBJECTIVE: To examine factors that affect the development of retinopathy after short-term inpatient management of diabetes. PATIENTS AND METHODS: The subjects were 143 patients with type 2 diabetes who were admitted for inpatient management of diabetes, and did not have retinopathy of the right eye at admission, and had an HbA1c level of > or =8.0%. We studied the characteristics of patients who developed retinopathy within one year after discharge. RESULTS: Between the admission date and one year after discharge, twenty-six patients developed retinopathy and the retinopathy subsequently regressed in 5 patients. The 26 patients who developed retinopathy had a significantly longer duration of diabetes (p<0.005), had a higher fasting blood glucose level at admission (p=0.06), and received insulin therapy during the admission at a higher rate (p=0.06) than the 117 patients without retinopathy. The magnitude of the reduction in HbA1c level at 3 months after discharge was smaller in the 13 patients who developed retinopathy within 3 months after discharge than in the 130 patients who did not. Among the 26 patients who developed retinopathy, the HbA1c level at one year after discharge of the 5 patients whose retinopathy regressed was lower than that of the 21 patients whose retinopathy did not regress (p=0.06). CONCLUSIONS: A long duration of diabetes, high fasting blood glucose level at admission, and treatment with insulin were associated with the development of retinopathy. Patients with these characteristics should undergo frequent fundus examinations after correction of hyperglycemia. The retinopathy was likely to improve if patients maintained strict glycemic control after discharge.

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PURPOSE: To prospectively assess the relationship between contraction of the anterior capsule opening and posterior capsule opacification (PCO) after cataract surgery in patients with diabetes mellitus. SETTING: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaragi, Japan. METHODS: This study comprised 45 patients (45 eyes) with diabetes mellitus who had cataract surgery. In all eyes, the anterior capsule opening area and degree of PCO were determined by diaphanoscopy using an anterior eye segment analysis system (EAS-100, Nidek, Inc.) 1 day and 1 year postoperatively. RESULTS: There was no correlation between the size of the anterior capsule opening area 1 day after surgery and the degree of PCO 1 year after surgery (Pearson correlation coefficient [r] = 0.041; P =.79). The percentage reduction in the anterior capsule opening area from 1 day to 1 year after surgery did not correlate with the degree of PCO 1 year after surgery (r = -0.08; P =.60). CONCLUSION: Contraction of the anterior capsule opening and PCO after cataract surgery cannot be explained by a common mechanism.

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Telemedicine was used for taking ocular fundus images of diabetic patients, which were subsequently sent by electronic mail to experienced ophthalmologists at a university hospital. The ophthalmologists provided reports on the patients to the internists. The objective of the study was to evaluate the effectiveness of this telemedicine system. A total of 279 diabetic patients were admitted to the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, for blood sugar control or for education on lifestyle between April, 1999, and October, 2000. The subjects did not have eye disease nor diabetic retinopathy when evaluated by an ophthalmologist (at either Yokohama City University Hospital or other facility) within 3 months before enrollment in the study. After dilation of the pupil, fundus images were taken of each eye from four angles using a nonmydriatic fundus camera. The images were transmitted by electronic mail to the Division of Ophthalmology of Tokyo University Branch Hospital along with other patient information. The ophthalmologists there evaluated the images on the screen according to Fukuda's classification of diabetic retinopathy. They sent ophthalmologic reports to the internists at the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, and recommended whether the patient should be seen by his/her regular ophthalmologist earlier than the next scheduled visit. Fundus images were obtained at the time of admission, at 1, 3, and 6 months after discharge, and at every 6 months thereafter. Out of the images of 1170 eyes obtained at various time points from the 279 patients, 1076 (92.0%) were successfully evaluated by the ophthalmologists at the University of Tokyo, while 60 (5.1%) could not be evaluated and there was a communication problem for the images of 34 eyes. The ophthalmologists determined that 5 eyes of 3 patients required further evaluation by the patient's regular ophthalmologist based on the images transferred by telemedicine. No patient dropped out during the study period.

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To examine the physiological role of the histamine H(2) receptor, histamine H(2) receptor-null mice were generated by homologous recombination. Histamine H(2) receptor-null mice, which developed normally and were fertile and healthy into adulthood, exhibited markedly enlarged stomachs and marked hypergastrinemia. The former was due to hyperplasia of gastric gland cells (small-sized parietal cells, enterochromaffin-like cells and mucous neck cells which were rich in mucin), but not of gastric surface mucous cells, which were not increased in number as compared with those in wild-type mice despite the marked hypergastrinemia. Basal gastric pH was slightly but significantly higher in histamine H(2) receptor-null mice. Although carbachol but not gastrin induced in vivo gastric acid production in histamine H(2) receptor-null mice, gastric pH was elevated by both muscarinic M(3) and gastrin antagonists. Thus, both gastrin and muscarinic receptors appear to be directly involved in maintaining gastric pH in histamine H(2) receptor-null mice. Interestingly, gastric glands from wild-type mice treated with an extremely high dose of subcutaneous lansoprazole (10 mg/kg body weight) for 3 months were very similar to those from histamine H(2) receptor-null mice. Except for hyperplasia of gastric surface mucous cells, the findings for gastric glands from lansoprazole-treated wild-type mice were almost identical to those from gastric glands from histamine H(2) receptor-null mice. Therefore, it is possible that the abnormal gastric glands in histamine H(2) receptor-null mice are secondary to the severe impairment of gastric acid production, induced by the histamine H(2) receptor disruption causing marked hypergastrinemia. Analyses of the central nervous system (CNS) of histamine H(2) receptor-null mice revealed these mice to be different from wild-type mice in terms of spontaneous locomotor activity and higher thresholds for electrically induced convulsions. Taken together, these results suggest that (1) gastrin receptors are functional in parietal cells in histamine H(2) receptor-null mice, (2) abnormal gastric glands in histamine H(2) receptor-null mice may be secondary to severe impairment of gastric acid production and secretion and (3) histamine H(2) receptors are functional in the central nervous system.

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PURPOSE: We studied the effects of the age and/or disease duration in diabetics on the progression of diabetic retinopathy (DR). METHODS: The population consisted of 3614 type 2 diabetes mellitus (DM) patients. The subjects were divided into three age groups (elderly, > or = 65 years old; middle-aged, 64-40 years old, and younger < 40 years old) for disease duration-adjusted comparison with and without DR and proliferative diabetic retinopathy (PDR). Then, in 503 patients with 8-year follow-up data available, the frequency of development/progression of DR and the rate of progression to PDR were compared among the three groups. Thirdly, in the elderly patients, DR prevalence and the frequency of the development/progression of DR were compared between two groups with different diabetes duration (> or = 6 years and < or = 5 years). RESULTS: The prevalence of DR increased significantly with age (P < 0.001). The prevalence of PDR decreased significantly with age (P < 0.001). The overall frequency of the development and/or progression of DR increased significantly with age (P = 0.002); however, age was not related to the frequency of progression to PDR. In the patients with diabetes duration of 6-15 years, the frequency of the development/progression of DR and of progression to PDR after an 8-year follow up tended to decrease with age. Elderly patients with a diabetes duration of > or = 6 years showed significantly higher rate of prevalence of DR and frequency of development/progression of DR in an 8-year period than those with diabetes of a shorter duration (P < 0.001 and P < 0.001, respectively). CONCLUSION: In elderly DM patients, the prevalence of DR was increased even in the short duration and development/progression rates of DR were increased, while the relative frequency of PDR was decreased. Older-onset DM patients appear to be at a lower risk for progression to PDR.

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