Low-cost thermoregulation of wild sloths revealed by heart rate and temperature loggers.

Arboreal herbivores require large digestive tracts for leaf fermentation and detoxification; however, they must also have a low body mass that allows them to reach the foliage. The three-toed sloth, Bradypus tridactylus, experiences this trade-off, as leaves comprise 97.2% of its diet. Their calorie intake is extremely low owing to the low available caloric density of leaves and slow digestive processes related to leaf fibre fermentation and secondary compound detoxification. Sloths may require a high body temperature to assist fermentation; however, thermogenesis is energy-consuming. To investigate how sloths accomplish thermoregulation using marginal energy, we attached heart rate (HR) and temperature loggers to wild B. tridactylus individuals inhabiting the Amazon rainforest and recorded their HR and body surface temperature (Tskin). Tskin changed with ambient temperature (Ta) but was higher than Ta in 99.2% of cases. Increases in Tskin and HR did not coincide, suggesting that the increases were not caused by thermogenesis. Instead, they may passively increase Tskin by selecting warmer microhabitats and sunbathing. Consequently, 90.5% of Tskin were within 27.6-36.0 °C while the Ta fluctuated between 21.5 and 42.9 °C. This low-cost thermoregulation results in a low HR. In this study, the mean HR during observation was approximately 38.4% of the expected value based on the mammalian allometric relationship between body mass and HR. Thus, these properties may contribute to the low metabolic rates of sloths, alleviating their restricted energy intake.

EFFICACY OF THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE WITH VITRECTOMY FOR RETINAL DETACHMENT ASSOCIATED WITH MYOPIC MACULAR HOLES.

PURPOSE: To evaluate the anatomical and functional outcome of the inverted internal limiting membrane (ILM) flap technique with vitrectomy for retinal detachment associated with macular hole (MHRD) in highly myopic eyes. METHODS: In this retrospective observational study, 21 eyes with MHRD that underwent vitrectomy with conventional ILM peeling (ILM-peeling group, n = 11) or the inverted ILM flap technique (ILM flap group, n = 10) combined with C3F8 tamponade were enrolled in this study. The initial retinal reattachment rate, macular hole closure rate, and postoperative visual acuity at the final visit were compared between the ILM-peeling group and ILM flap group. RESULTS: There was no significant difference in the retinal reattachment rate between ILM-peeling and ILM flap groups (91% and 100%, respectively). The macular hole closure rate in the ILM flap group was 80% (8 of 10 eyes), and was significantly higher than 36% (4 of 11 eyes) in the ILM-peeling group (P = 0.039). Among 12 eyes that achieved macular hole closure, there was no significant difference in median visual acuity after vitrectomy between the ILM flap group and ILM-peeling group (logMAR unit [Snellen acuity]: 1.0 [20/200] and 0.76 [20/125], respectively, P = 0.300). CONCLUSION: Compared with conventional ILM peeling, the inverted ILM flap technique was more effective for macular hole closure after vitrectomy for MHRD in myopic eye but showed no advantage in the postoperative visual outcome in this study.

PERSISTENT OVERPRODUCTION OF INTRAOCULAR VASCULAR ENDOTHELIAL GROWTH FACTOR AS A CAUSE OF LATE VITREOUS HEMORRHAGE AFTER VITRECTOMY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: The purpose of this study was to investigate whether vitreous levels of vascular endothelial growth factor (VEGF) predict late vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy, and how VEGF level changes in patients with postoperative late VH. METHODS: Eighty-five eyes of 68 patients with proliferative diabetic retinopathy who underwent vitrectomy were analyzed retrospectively. Vitreous samples were collected from eyes undergoing primary vitrectomy and from eyes with late VH undergoing second vitrectomy. Vitreous VEGF levels were measured using enzyme-linked immunosorbent assay. The relationship between VEGF level and late VH (>4 weeks) occurring during follow-up as well as clinical findings, and changes in VEGF level in eyes with late VH undergoing second vitrectomy were analyzed. RESULTS: Late VH occurred in 20 (24%) of 85 eyes, and 9 eyes required second vitrectomy. Vitreous levels of VEGF were significantly higher (median: 1,945 pg/mL; P < 0.0001) in eyes with late VH than in those without. Preexisting iris neovascularization (P < 0.0001), hypertension (P = 0.002), and proteinuria (P = 0.040) were also significant risk factors of late VH. Multivariate logistic regression analysis showed that a higher vitreous VEGF level was independently associated with a risk of postoperative late VH in patients with proliferative diabetic retinopathy (odds ratio: 20.8, 95% confidence interval: 2.72-159.47; P = 0.003). Vitreous VEGF level at second vitrectomy in patients with late VH was significantly lower compared with that at primary vitrectomy, but remained elevated (median: 1,610 pg/mL; P = 0.023). CONCLUSION: In patients with proliferative diabetic retinopathy, high intraocular VEGF level at primary vitrectomy was identified as an independent risk factor of postoperative late VH. Persistent overproduction of intraocular VEGF may be associated with postoperative late VH.

Pericentric H3K9me3 Formation by HP1 Interaction-defective Histone Methyltransferase Suv39h1.

Pericentric regions form epigenetically organized, silent heterochromatin structures that accumulate histone H3 lysine 9 tri-methylation (H3K9me3) and heterochromatin protein 1 (HP1), a methylated H3K9-binding protein. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1. However, the importance of HP1 interaction for Suv39h-mediated H3K9me3 formation at the pericentromere is not well characterized. To address this question, we introduced HP1 binding-defective, N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient cells. Pericentric H3K9me3-positive cells were not detected by endogenous-level expression of ΔN. Notably, ΔN could induce pericentric accumulation of H3K9me3 as wild type Suv39h1 did if it was overexpressed. These findings demonstrate that the N-terminal region of Suv39h1, presumably via HP1-Suv39h1 interaction, is required for Suv39h1-mediated pericentric H3K9me3 formation, but can be overridden if Suv39h1 is overproduced, indicating that Suv39h1-mediated heterochromatin formation is controlled by multiple modules, including HP1.

Knockout mouse production assisted by Blm knockdown.

Production of knockout mice using targeted embryonic stem cells (ESCs) is a powerful approach for investigating the function of specific genes in vivo. Although the protocol for gene targeting via homologous recombination (HR) in ESCs is already well established, the targeting efficiency varies at different target loci and is sometimes too low. It is known that knockdown of the Bloom syndrome gene, BLM, enhances HR-mediated gene targeting efficiencies in various cell lines. However, it has not yet been investigated whether this approach in ESCs is applicable for successful knockout mouse production. Therefore, we attempted to answer this question. Consistent with previous reports, Blm knockdown enhanced gene targeting efficiencies for three gene loci that we examined by 2.3-4.1-fold. Furthermore, the targeted ESC clones generated good chimeras and were successful in germline transmission. These data suggest that Blm knockdown provides a general benefit for efficient ESC-based and HR-mediated knockout mouse production.

Hormonal regulation and developmental role of Krüppel homolog 1, a repressor of metamorphosis, in the silkworm Bombyx mori.

Juvenile hormone (JH) has an ability to repress the precocious metamorphosis of insects during their larval development. Krüppel homolog 1 (Kr-h1) is an early JH-inducible gene that mediates this action of JH; however, the fine hormonal regulation of Kr-h1 and the molecular mechanism underlying its antimetamorphic effect are little understood. In this study, we attempted to elucidate the hormonal regulation and developmental role of Kr-h1. We found that the expression of Kr-h1 in the epidermis of penultimate-instar larvae of the silkworm Bombyx mori was induced by JH secreted by the corpora allata (CA), whereas the CA were not involved in the transient induction of Kr-h1 at the prepupal stage. Tissue culture experiments suggested that the transient peak of Kr-h1 at the prepupal stage is likely to be induced cooperatively by JH derived from gland(s) other than the CA and the prepupal surge of ecdysteroid, although involvement of unknown factor(s) could not be ruled out. To elucidate the developmental role of Kr-h1, we generated transgenic silkworms overexpressing Kr-h1. The transgenic silkworms grew normally until the spinning stage, but their development was arrested at the prepupal stage. The transgenic silkworms from which the CA were removed in the penultimate instar did not undergo precocious pupation or larval-larval molt but fell into prepupal arrest. This result demonstrated that Kr-h1 is indeed involved in the repression of metamorphosis but that Kr-h1 alone is incapable of implementing normal larval molt. Moreover, the expression profiles and hormonal responses of early ecdysone-inducible genes (E74, E75, and Broad) in transgenic silkworms suggested that Kr-h1 is not involved in the JH-dependent modulation of these genes, which is associated with the control of metamorphosis.

Noninvasive vascular imaging of ruptured retinal arterial macroaneurysms by Doppler optical coherence tomography.

BACKGROUND: To describe Doppler optical coherence tomography (OCT) imaging of ruptured retinal arterial macroaneurysms (RAMs). METHODS: Four eyes of four patients with ruptured RAMs were prospectively studied. Vascular imaging was obtained using swept-source Doppler OCT, and compared with indocyanine green angiography images. RESULTS: En face projection of Doppler OCT images clearly showed RAMs at the corresponding locations of lesions in the indocyanine green angiography images. In Doppler OCT images, RAMs were located in the inner retina in three eyes and in the medium layer of the retina in one eye. In one eye, detection of RAMs by standard OCT was difficult because of the presence of inner retinal hemorrhage. In one eye, disappearance of blood flow after direct laser photocoagulation could be confirmed by Doppler OCT images. CONCLUSIONS: Doppler OCT imaging may potentially function as a noninvasive complementary procedure with indocyanine green angiography.

Complete pyridine-nucleotide-specific conversion of an NADH-dependent ferredoxin reductase.

The coenzyme specificity of enzymes is one of the critical parameters for the engineered production of biological compounds using bacteria. Since NADPH is produced abundantly in photosynthetic organisms, conversion of an NADH-specific enzyme into an NADPH-specific one is a useful approach for the efficient carbon-neutral production of biological compounds in photosynthetic organisms. In the present study, an NADH-specific ferredoxin reductase component, BphA4 of biphenyl dioxygenase BphA from Acidovorax sp. strain KKS102, was changed to an NADPH-dependent form using a method combining structure-based systematic mutations and site-directed random mutagenesis. The resultant CRG mutant, in which Glu175-Thr176-Gln177 of an NADH-recognition loop in the wild-type BphA4 was replaced with Cys175-Arg176-Gly177, was highly specific and active for NADPH, and its biochemical and structural properties for NADPH were nearly the same as those of the wild-type BphA4 for NADH. In addition, this mutation project was assessed by a semi-empirical prediction method of mutation effects, and the results suggested that the CRG mutant was one of the best NADPH-specific mutants.

Pericentric heterochromatin generated by HP1 protein interaction-defective histone methyltransferase Suv39h1.

Pericentric regions form epigenetically organized silent heterochromatin structures that accumulate histone H3 lysine 9 trimethylation (H3K9me3) and HP1. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1, a methylated H3K9-binding protein. However, it is not well characterized how HP1 interaction is important for Suv39h accumulation and Suv39h-mediated H3K9me3 formation at the pericentromere. To address this, we introduced the HP1 binding-defective N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient embryonic stem cells. Interestingly, pericentric accumulation of ΔN and ΔN-mediated H3K9me3 was observed to recover, but HP1 accumulation was only marginally restored. ΔN also rescued DNA methyltransferase Dnmt3a and -3b accumulation and DNA methylation of the pericentromere. In contrast, other pericentric heterochromatin features, such as ATRX protein association and H4K20me3, were not recovered. Finally, derepressed major satellite repeats were partially silenced by ΔN expression. These findings clearly showed that the Suv39h-HP1 binding is dispensable for pericentric H3K9me3 and DNA methylation, but this interaction and HP1 recruitment/accumulation seem to be crucial for complete formation of heterochromatin.

Correlation of complement fragment C5a with inflammatory cytokines in the vitreous of patients with proliferative diabetic retinopathy.

PURPOSE: To determine the vitreous concentration of complement fragment C5a in patients with proliferative diabetic retinopathy (PDR) and the relation between C5a and inflammatory cytokines including vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). METHODS: Vitreous samples were obtained at the time of vitrectomy from 12 eyes of 11 PDR patients and from 11 eyes of 11 patients without diabetes with macular disease (controls). Vitreous and serum concentrations of human C5a, VEGF, and MCP-1 were quantified using FACS Caliber flow cytometer. RESULTS: Vitreous concentration of C5a increased significantly in patients with PDR [median (range): 928.7 (46.6 to 3,319.4) pg/ml] compared with controls [58.7 (22.2 to 1,432.4) pg/ml; p < 0.01]. In PDR patients, vitreous concentration of C5a correlated significantly with those of VEGF (p < 0.05) and MCP-1 (p < 0.05). CONCLUSIONS: Our results suggest that C5a may play an important role in the pathogenesis of PDR and work in concert with inflammatory cytokines such as VEGF and MCP-1 in pathological angiogenesis.

Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

Effects of heat degradation of betanin in red beetroot (Beta vulgaris L.) on biological activity and antioxidant capacity.

Betanin is a red pigment of red beetroot (Beta vulgaris L.), providing the beneficial effects to maintain human health. Betanin is involved in the characteristic red color of red beetroot, and used as an edible dye. Betanin is known to be a highly unstable pigment, and water solutions of betanin are nearly fully degraded after heating at 99°C for 60 min in the experimental conditions of this study. The present study investigated the effects of red beetroot juice (RBJ) and betanin on immune cells, and found that stimulation with RBJ and betanin induces interleukin (IL)-1ß, IL-8, and IL-10 mRNA in a human monocyte derived cell line, THP-1 cells. This mRNA induction after stimulation with RBJ and betanin was not significantly changed after heat treatment when attempting to induce degradation of the betanin. Following these results, the effects of heat degradation of betanin on the inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264 cells and the antioxidant capacity were investigated. The results showed that the inhibition activity of RBJ and betanin with the LPS induced NO production is not altered after heat degradation of betanin. In addition, the results of FRAP (ferric reducing antioxidant power) and DPPH (1,1-Diphenyl-2-picrylhydrazyl) assays indicate that a not inconsiderable degree of the antioxidant capacity of RBJ and betanin remained after heat degradation of betanin. These results suggest that it is important to consider the effects of degradation products of betanin in the evaluation of the beneficial effects of red beetroot on health.

Effects of chondroitin sulfate oligosaccharides on osteoclast differentiation of RAW264 cells, and myotube differentiation of C2C12 cells.

Chondroitin sulfate (CS) is a glycosaminoglycan, and CS derived from various animal species is used in drugs and food supplements to alleviate arthralgia. The CS is a high molecular weight compound, and hydrolysis of CS by intestinal microbiota is thought to be required for absorption in mammalians. Chondroitin sulfate oligosaccharides (Oligo-CS) are produced by hydrolysis with subcritical water from CS isolated from a species of skate, Raja pulchra for the improvement of bioavailability. The present study conducted in vitro experiments using murine cell lines, to compare the biological activities of Oligo-CS and high molecular weight CS composed with the similar disaccharide isomer units of D-glucuronic acid and N-acetyl-D-glucosamine (CS-C). The results show that Oligo-CS inhibits osteoclast differentiation of RAW264 cells significantly at lower concentrations than in CS. The cell viability of a myoblast cell line, C2C12 cells, was increased when the cells were grown in a differentiated medium for myotubes with Oligo-CS, where there were no effects on the cell viability in CS. These results suggest that in vitro Oligo-CS exhibits stronger bioactivity than high-molecular weight CS.

Preparation and Characterization of Electric Double-Layer Capacitors Having a 3D Stainless-Steel Fiber Sheet as the Current Collector.

One strategy to improve the performance of electric double-layer capacitors (EDLCs) is changing the current collector material. In this study, a three-dimensional porous current collector comprising stainless-steel fibers is fabricated using a relatively simple method. Capacitor properties of the EDLC using this unique current collector are characterized by cyclic voltammetry and charge-discharge tests. The voltammograms of the EDLC develop a more butterfly shape and an increased specific capacity at higher electrolyte concentrations. It shows reversible charge-discharge potential profiles, little capacity degradation (∼98% of the initial capacity at 1000th cycle), and a good rate performance at higher electrolyte concentrations (90% capacity retention for 2.5 times increase in discharge current). Its capacitance values (95-99 F g-1) are roughly twice the specific capacitance of an EDLC using the flat stainless-steel plate current collector (51 F g-1) without any performance degradation even at a higher loading of electrode active materials. Based on the AC impedance analysis, these good properties are attributed to the reduction in several resistances compared to the case of a flat stainless-steel plate: (i) the contact resistance between the electrode active material and the current collector, (ii) the resistance of the electrolyte in the finely branched space formed by the fibers and the active material, and (iii) the resistance in the diffusion layer. Increasing the electrolyte concentration further reduces the latter two resistances and the bulk electrolyte resistance, resulting in higher performance of the EDLC using the stainless-steel fiber sheet current collector.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

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.

Long-Term Outcome of Eyes with Vitrectomy for Submacular and/or Vitreous Hemorrhage in Neovascular Age-Related Macular Degeneration.

PURPOSE: To study long-term clinical outcomes in patients with submacular hemorrhage (SMH) and/or vitreous hemorrhage (VH) associated with neovascular age-related macular degeneration (nAMD) and the real-world clinical situation of adding anti-VEGF therapy after pars plana vitrectomy (PPV). METHODS: In this retrospective case series, 25 eyes with SMH and/or VH associated with nAMD were treated by PPV and followed up for at least 24 months. When exudative changes were unresolved or recurred after PPV, additional intravitreal anti-VEGF therapy was given. RESULTS: The reasons for performing PPV were SMH (8 eyes) and VH (17 eyes) associated with nAMD. Mean best-corrected visual acuity (BCVA) of eyes with SMH improved significantly at 6 months (P < 0.01) and 12 months (P < 0.05) after PPV. Mean BCVA of eyes with VH improved at 1, 3, 6, 12, 18, and 24 months (P < 0.01) and at the final visit (P < 0.05). Post-PPV anti-VEGF therapy was initiated in 6 of 8 (75.0%) eyes with SMH and 7 of 17 (47.1%) eyes with VH. Of the 13 eyes given anti-VEGF therapy after PPV, 11 eyes had anti-VEGF therapy initiated within 10 months after surgery. Dry macula rate after PPV was 50.0% in SMH and 70.6% in VH. CONCLUSIONS: BCVA improved in eyes with SMH at 6 and 12 months after PPV, and the BCVA was maintained until the end of the study. BCVA improved significantly in eyes with VH at all time points after PPV. In eyes undergoing PPV for nAMD, recurrence of exudative changes after 11 months from the initial PPV was rare.

In vitro anti-inflammatory and anti-lipid accumulation properties of taxifolin-rich extract from the Japanese larch, Larix kaempferi.

The Japanese larch, (Larix kaempferi) is known to contain abundant taxifolin (dihydroquercetin) in its xylem. In this study, to assess the bioactivities of taxifolin rich methanol extract of L. kaempferi (LK-ME), anti-inflammatory effect, and the anti-lipid accumulation effect of LK-ME were investigated. The results showed that nitric oxide (NO) and reactive oxygen species (ROS) were reduced after treatment with LK-ME, and that lipid accumulation in adipocyte differentiated 3T3-L1 cells was inhibited after the cells were grown in medium containing LK-ME. Taxifolin, the major compound contained in LK-ME, and its related compounds, quercetin and luteolin also exhibited similar effects with LK-ME. The LK-ME exhibits relatively strong anti-inflammatory and anti-lipid accumulation activities compared with that of similar amounts of taxifolin contained in LK-ME, suggesting that other minor compounds contained in LK-ME is involved in the effects. These results indicate the potential of taxifolin-rich L. kaempferi extract for use as a supplement to prevent excess inflammation and obesity.

Successful Treatment of Necrotizing Retinitis with Epstein-Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection.

PURPOSE: To present a case of necrotizing retinitis with Epstein-Barr virus (EBV)-positive ocular fluid in a patient with sudden unilateral vision loss, which was successfully treated with intravitreal methotrexate (MTX) injections. METHODS: Retrospective case report. RESULTS: An 83-year-old female who had been on methylprednisolone for 20 years due to interstitial pneumonia developed vitreous opacity and extensive necrotizing retinitis with retinal hemorrhage sparing the posterior pole in the left eye. Multiplex polymerase chain reaction (PCR) for viral DNA using vitreous sample was positive for EBV but negative for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Real-time PCR detected EBV-DNA in aqueous humor but not in peripheral blood sample. Serologic testing was negative for Toxoplasma gondii, syphilis, and HIV. The patient did not respond to systemic ganciclovir or acyclovir. Subsequent treatment with intravitreal MTX resulted in immediate clinical improvement correlating with a decrease in copy number of EBV-DNA. CONCLUSION: Intravitreal MTX may be an effective treatment option for patients with necrotizing retinitis and EBV-positive ocular fluid not responding to conventional antiviral therapy.

Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study.

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.