The relationship between blood vitamin A levels and diabetic retinopathy: a population-based study.

We assessed the relationship between blood vitamin A levels and the risk of diabetic retinopathy. The study was population-based epidemiological study for 11,727 participants aged 40 or older who participated in the Korean National Health and Nutrition Examination Survey. Vitamin A in the blood was classified into quartiles. Diabetic retinopathy was diagnosed by the Early Treatment for Diabetic Retinopathy Study. After adjusting confounding variables such as age, sex, smoking, cholesterol, diabetes prevalence period, glycated hemoglobin levels, and high blood pressure, the odd ratio (OR) of vitamin A at quartile level 4 for diabetic retinopathy was 0.32 (95% confidence interval [CI], 0.14-0.72, P for trend < 0.001). In male, the OR of quartile 3 level vitamin A for diabetic retinopathy was 0.11 (95% CI, 0.01-0.69, P for trend = 0.010). In adults under the age of 60, the OR of vitamin A at quartile level 3 for diabetic retinopathy was 0.10. (95% CI, 0.03-0.29, P for trend < 0.001). Serum vitamin A high levels are associated with low risk of diabetic retinopathy. Particularly, there is a more effective relationship in male and adults under the age of 60.

Are dietary intake parameters of vitamin A, carotene, retinol appropriate factors to evaluate the risk of diabetic retinopathy?

The purpose of this study is to investigate whether dietary parameters of vitamin A, carotene, and retinol are sufficient for assessing the risk of diabetic retinopathy (DR). This was a population-based cross sectional study using systematic stratified, multilevel, nationwide, clustered sampling methods. From 2008 to 2012, 1948 subjects aged ≥ 40 years who participated in the Korean National Health and Nutrition Examination Survey were included. Participants underwent standardized interviews, dietary vitamin A estimation, carotene and retinol level evaluation, and eye examination. Daily dietary intake was evaluated using data in the form of a single 24-hour recall. The odds ratio (OR) of dietary vitamin A between extreme quartiles for DR was 0.72 (95% confidence interval [CI], 0.45-1.16, P for trend = .462) after adjusting for covariates such as age, sex, hypertension, hemoglobin A1c levels, and diabetes duration. The adjusted OR of dietary carotene between extreme quartiles for DR was 0.65 (95% CI, 0.39-1.09, P for trend = .220). The adjusted OR of dietary retinol between extreme quartiles for DR was 1.05 (95% CI, 0.62-1.80, P for trend = .279). There was no statistical significance in proliferative DR and Vision-threatening Dr Our study did not find evidence that the risk of DR is correlated with dietary vitamin A levels. Dietary intake parameters of vitamin A, carotene, and retinol might be insufficient to determine the association between the risk of Dr To demonstrate an association for the risk of DR, the use of serum information and not dietary information is needed.

Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection.

A-Kinase anchoring protein 1 (AKAP1) is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis by anchoring several proteins, including protein kinase A, to the outer mitochondrial membrane. Glaucoma is a complex, multifactorial disease characterized by a slow and progressive degeneration of the optic nerve and retinal ganglion cells (RGCs), ultimately resulting in vision loss. Impairment of the mitochondrial network and function is linked to glaucomatous neurodegeneration. Loss of AKAP1 induces dynamin-related protein 1 dephosphorylation-mediated mitochondrial fragmentation and loss of RGCs. Elevated intraocular pressure triggers a significant reduction in AKAP1 protein expression in the glaucomatous retina. Amplification of AKAP1 expression protects RGCs from oxidative stress. Hence, modulation of AKAP1 could be considered a potential therapeutic target for neuroprotective intervention in glaucoma and other mitochondria-associated optic neuropathies. This review covers the current research on the role of AKAP1 in the maintenance of mitochondrial dynamics, bioenergetics, and mitophagy in RGCs and provides a scientific basis to identify and develop new therapeutic strategies that could protect RGCs and their axons in glaucoma.

Yearly trends in the incidence of ocular traumas and the effects of COVID-19 pandemic: a nationwide population-based study of Korean data.

Background: Ocular trauma can cause irreversible visual impairment, and its incidence is higher than that of other ocular diseases in young patients. Past studies on ocular trauma have been limited in terms of small sample sizes, specific age groups, or a short period of assessment. Moreover, no studies have yet investigated the effects of changes in lifestyle during the coronavirus disease 2019 (COVID-19) pandemic on these trends. Therefore, we aimed to determine the yearly trends in the incidence of various ocular traumas over a 10-year period (2011-2020), and to evaluate the effects of the COVID-19 pandemic on these trends. Methods: In this nationwide, population-based, cross-sectional study, we recorded the yearly number of patients diagnosed with hyphema and those who underwent open reduction surgery for orbital blowout fracture (BOF), primary closure of the cornea or sclera (PCCS), and intraocular foreign body (IOFB) removal. Results: While the annual incidence of closed-globe injuries and PCCS decreased significantly in age groups less than 60 years over the past 10 years, the incidence of surgery for BOF and IOFB increased significantly in age groups greater than or equal to 60 years during the same period. When the 2020 data were compared with data from 2011-2019, hyphema showed the largest decrease (47.24%) in incidence among all ocular traumas, reaching significance in those ages less than 20 years (64.41%, P=0.004); the incidence of surgery for BOF also showed the largest decrease, in patients age less than 20 years. In the population age greater than or equal to 60 years, higher incidences of surgery for BOF and IOFB were observed (13.08% and 25.53%, respectively). Conclusions: While the incidence of closed-globe injuries has decreased over the past 10 years in age groups less than 60 years, those age with more than 60 years have become more prone to serious ocular trauma. During the COVID-19 era, the incidence of closed-globe injuries fell markedly in patients younger than 20 years of the age, possibly due to social distancing which involved school closures and reduction in outdoor activities.

A Semantic Data-Based Distributed Computing Framework to Accelerate Digital Twin Services for Large-Scale Disasters.

As natural disasters become extensive, due to various environmental problems, such as the global warming, it is difficult for the disaster management systems to rapidly provide disaster prediction services, due to complex natural phenomena. Digital twins can effectively provide the services using high-fidelity disaster models and real-time observational data with distributed computing schemes. However, the previous schemes take little account of the correlations between environmental data of disasters, such as landscapes and weather. This causes inaccurate computing load predictions resulting in unbalanced load partitioning, which increases the prediction service times of the disaster management agencies. In this paper, we propose a novel distributed computing framework to accelerate the prediction services through semantic analyses of correlations between the environmental data. The framework combines the data into disaster semantic data to represent the initial disaster states, such as the sizes of wildfire burn scars and fuel models. With the semantic data, the framework predicts computing loads using the convolutional neural network-based algorithm, partitions the simulation model into balanced sub-models, and allocates the sub-models into distributed computing nodes. As a result, the proposal shows up to 38.5% of the prediction time decreases, compared to the previous schemes.

Prediction of Visual Outcomes After Diabetic Vitrectomy Using Clinical Factors From Common Data Warehouse.

Purpose: We sought to analyze the visual outcome and systemic prognostic factors for diabetic vitrectomy and predicted outcomes using these factors. Methods: This was a multicenter electronic medical records (EMRs) review study of 1504 eyes with type 2 diabetes that underwent vitrectomy for proliferative diabetic retinopathy at 6 university hospitals. Demographics, laboratory results, intra-operative findings, and visual acuity (VA) values were analyzed and correlated with visual outcomes at 1 year after the vitrectomy. Prediction models for visual outcomes were obtained using machine learning. Results: At 1 year, VA was 1.0 logarithm of minimal angle resolution (logMAR) or greater (poor visual outcome group) in 456 eyes (30%). Baseline visual acuity, duration of diabetes treatment, tractional membrane, silicone oil tamponade, smoking, and vitreous hemorrhage correlated with logMAR VA at 1 year (r = 0.450, -0.159, 0.221, 0.280, 0.067, and -0.105; all P ≤ 0.036). An ensemble decision tree model trained using all variables generated accuracy, specificity, F1 score (the harmonic means of which precision and sensitivity), and receiver-operating characteristic curve area under curve values of 0.77, 0.66, 0.85, and 0.84 for the prediction of poor visual outcomes at 1 year after vitrectomy. Conclusions: Visual outcome after diabetic vitrectomy is associated with pre- and intra-operative findings and systemic factors. Poor visual outcome after diabetic vitrectomy was predictable using clinical factors. Intensive care in patients who are predicted to result in poor vision may limit vision loss resulting from type 2 diabetes. Translational Relevance: This study demonstrates that a real world EMR big data could predict outcome after diabetic vitrectomy using clinical factors.

Characteristics of major and macular branch retinal vein occlusion.

We compared the aqueous profiles, baseline characteristics, and clinical outcomes of 54 eyes with macular edema secondary to major branch retinal vein occlusion (BRVO) and macular BRVO. We also identified the characteristics of poor responders to anti-vascular endothelial growth factor (VEGF) injections. Aqueous inflammatory cytokine and VEGF concentrations were significantly higher in major BRVO. In optical coherence tomography, major BRVO had a higher proportion with subretinal fluid, disorganization of retinal inner layers, and ellipsoid zone disruption. Comparing the clinical outcomes, major BRVO required more intravitreal anti-VEGF injections and had a poorer visual prognosis in the first 12 months. A significantly higher proportion of patients with major BRVO required additional treatments after 6 months compared to macular BRVO. Patients who responded poorly to anti-VEGF had higher aqueous VEGF levels and central subfield thickness (CST) at baseline. In conclusion, major BRVO patients required more and longer treatments, and had worse visual prognoses. BRVO that responds poorly to anti-VEGF had greater CST and higher aqueous VEGF levels at baseline.

A Novel Digital Twin Architecture with Similarity-Based Hybrid Modeling for Supporting Dependable Disaster Management Systems.

Disaster management systems require accurate disaster monitoring and prediction services to reduce damages caused by natural disasters. Digital twins of natural environments can provide the services for the systems with physics-based and data-driven disaster models. However, the digital twins might generate erroneous disaster prediction due to the impracticability of defining high-fidelity physics-based models for complex natural disaster behavior and the dependency of data-driven models on the training dataset. This causes disaster management systems to inappropriately use disaster response resources, including medical personnel, rescue equipment and relief supplies, to ensure that it may increase the damages from the natural disasters. This study proposes a digital twin architecture to provide accurate disaster prediction services with a similarity-based hybrid modeling scheme. The hybrid modeling scheme creates a hybrid disaster model that compensates for the errors of physics-based prediction results with a data-driven error correction model to enhance the prediction accuracy. The similarity-based hybrid modeling scheme reduces errors from the data dependency of the hybrid model by constructing a training dataset using similarity assessments between the target disaster and the historical disasters. Evaluations in wildfire scenarios show that the digital twin decreases prediction errors by approximately 50% compared with those of the existing schemes.

Aqueous Humor Analyses in Patients with Diabetic Retinopathy Who Had Undergone Panretinal Photocoagulation.

Purpose: To determine the associations between aqueous humor cytokine levels and the severity of diabetic retinopathy and the prior panretinal photocoagulation (PRP) status of patients with diabetic macular edema (DME). Methods: We divided 98 DME patients into those with nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and PRP patients. We compared the concentrations of interleukin- (IL-) 1ß, IL-6, IL-8, IL-10, and IL-17; placental growth factor (PlGF); and vascular endothelial growth factor (VEGF) in the aqueous humors. We subclassified PRP patients by the interval between PRP and aqueous sampling and analyzed the associations between aqueous cytokine levels and this interval. Results: The aqueous humor levels of IL-6, IL-8, VEGF, and PlGF were significantly higher in the PDR group than in the NPDR group. The PlGF and VEGF levels in the PDR group were significantly higher than those in the PRP group. On PRP subgroup analyses, patients who had undergone PRP within 6 months prior exhibited higher levels of VEGF, PlGF, and TNF-α than did those who had undergone PRP more than 12 months prior. The TNF-α level of the PRP subgroup treated within 6 months prior was significantly higher than that of the PDR group. Regression analyses showed that the levels of VEGF, PlGF, and TNF-α decreased significantly as the interval between PRP and aqueous sampling became longer. Conclusions: PDR patients exhibited higher concentrations of VEGF and certain inflammatory cytokines than did NPDR and PRP patients. In the latter patients, the intraocular VEGF and inflammatory cytokine levels fell gradually over time.

Predicting persistent central serous chorioretinopathy using multiple optical coherence tomographic images by deep learning.

We sought to predict whether central serous chorioretinopathy (CSC) will persist after 6 months using multiple optical coherence tomography (OCT) images by deep convolutional neural network (CNN). This was a multicenter, retrospective, cohort study. Multiple OCT images, including B-scan and en face images of retinal thickness (RT), mid-retina, ellipsoid zone (EZ) layer, and choroidal layer, were collected from 832 eyes of 832 CSC patients (593 self-resolving and 239 persistent). Each image set and concatenated set were divided into training (70%), validation (15%), and test (15%) sets. Training and validation were performed using ResNet50 CNN architecture for predicting CSC requiring treatment. Model performance was analyzed using the test set. The accuracy of prediction was 0.8072, 0.9200, 0.6480, and 0.9200 for B-scan, RT, mid-retina, EZ, and choroid modalities, respectively. When image sets with high accuracy were concatenated, the accuracy was 0.9520, 0.8800, and 0.9280 for B-scan + RT, B-scan + EZ, and EZ + RT, respectively. OCT B-scan, RT, and EZ en face images demonstrated good performances for predicting the prognosis of CSC using CNN. The performance improved when these sets were concatenated. The results of this study can serve as a reference for choosing an optimal treatment for CSC patients.

Real-world treatment intensities and pathways of macular edema following retinal vein occlusion in Korea from Common Data Model in ophthalmology.

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

Long-term prediction models for vision-threatening diabetic retinopathy using medical features from data warehouse.

We sought to evaluate the performance of machine learning prediction models for identifying vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus using only medical data from data warehouse. This is a multicenter electronic medical records review study. Patients with type 2 diabetes screened for diabetic retinopathy and followed-up for 10 years were included from six referral hospitals sharing same electronic medical record system (n = 9,102). Patient demographics, laboratory results, visual acuities (VAs), and occurrence of VTDR were collected. Prediction models for VTDR were developed using machine learning models. F1 score, accuracy, specificity, and area under the receiver operating characteristic curve (AUC) were analyzed. Machine learning models revealed F1 score, accuracy, specificity, and AUC values of up 0.89, 0.89.0.95, and 0.96 during training. The trained models predicted the occurrence of VTDR at 10-year with F1 score, accuracy, and specificity up to 0.81, 0.70, and 0.66, respectively, on test set. Important predictors included baseline VA, duration of diabetes treatment, serum level of glycated hemoglobin and creatinine, estimated glomerular filtration rate and blood pressure. The models could predict the long-term occurrence of VTDR with fair performance. Although there might be limitation due to lack of funduscopic findings, prediction models trained using medical data can facilitate proper referral of subjects at high risk for VTDR to an ophthalmologist from primary care.

CLINICAL FEATURES OF INTRAVITREAL DEXAMETHASONE IMPLANTATION IN VITRECTOMIZED EYES OF PATIENTS WITH DIABETIC MACULAR EDEMA.

PURPOSE: To identify the clinical outcomes of intravitreal dexamethasone implantation (IVD) in previously vitrectomized eyes of patients with diabetic macular edema. METHOD: We performed a retrospective observational study. We recorded central subfield thickness, best-corrected visual acuity, and intraocular pressure up to 12 months after IVD implant placement. We compared the duration of IVD action, intraocular pressure trends, and the prevalence of ocular hypertension after the first IVD treatment of nonvitrectomized and vitrectomized eyes. We also compared the central subfield thickness, best-corrected visual acuity, number of IVD treatments, and prevalence of ocular hypertension between the 2 groups after 12 months. RESULTS: We found no significant between-group differences in the central subfield thickness, best-corrected visual acuity, or the prevalence of ocular hypertension during treatment. However, the duration of action of the first IVD treatment was significantly shorter in vitrectomized eyes, and these eyes required more IVD treatments during the 12-month follow-up period. The maximal average intraocular pressure was observed at 2 months after the first IVD treatment in the nonvitrectomized group, but 1 month after the first IVD treatment in the vitrectomized group. CONCLUSION: These findings suggest that the IVD pharmacokinetics and pharmacodynamics differ between vitrectomized and nonvitrectomized eyes. Nevertheless, given the relatively long-lasting effectiveness of the treatment and the good clinical results, consecutive IVD treatments may be beneficial for patients with diabetic macular edema with previously vitrectomized eyes.

An Enhanced Water Solubility and Stability of Anthocyanins in Mulberry Processed with Hot Melt Extrusion.

Mulberry fruits are rich sources of anthocyanins that exhibit beneficial biological activity. These anthocyanins become instable in an aqueous media, leading to their low bioavailability. In this study, a colloidal dispersion was produced by processing mulberry samples with hot-melt extrusion. In this process, hydrophilic polymer matrices were used to disperse the compound in an aqueous media. Mulberry samples were processed with hot-melt extrusion and in the presence of an ionization agent and sodium alginate to form mulberry-extrudate solid formulations. The particle size of mulberry-extrudate solid formulations decreased, while the total phenol content, the total anthocyanin content, and solubility increased. Fourier transform infrared spectroscopy (FT-IR) revealed that mulberry-extrudate solid formulations now contained new functional groups, such as -COOH group. We investigated whether mulberry-extrudate solid formulations had a positive impact on the stability of anthocyanins. The non-extrudate mulberry sample and mulberry-extrudate solid formulations were incubated with a simulated gastric fluid system and an intestinal fluid system. The number of released anthocyanins was determined with HPLC. We found that anthocyanins were released rapidly from non-extrudate mulberry extract. Mulberry-extrudate solid formulations contained a large number of available anthocyanins even after being incubated for 180 min in the intestinal fluid system. Thus, hot-melt extrusion enhanced water solubility and stability of anthocyanins with the prolonged release.

Aqueous humor analyses of diabetic macular edema patients with subretinal fluid.

We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Risk factors for ocular hypertension after intravitreal dexamethasone implantation in diabetic macular edema.

We designed a retrospective observational study to identify factors associated with ocular hypertension [OHTN, defined as intraocular pressure (IOP) > 25 mmHg] after intravitreal dexamethasone (IVD) implantation in diabetic macular edema (DME) patients. We measured IOP monthly after placement of an IVD implant, and identified the trend of IOP, incidence of OHTN, and its associated systemic or ocular factors. On average, IOP was highest at 2 months after IVD implantation. Of 84 DME patients who received an IVD implant, 3 (3.57%) presented with an IOP ≥ 25 mmHg at 1 month after implantation, 6 (7.14%) at 2 months, and 2 (2.38%) at 3 months. Compared with the non-OHTN group, the OHTN group had significantly shorter axial lengths and were younger. Logistic regression analysis revealed that axial length < 23.00 mm and age < 57 years were associated with OHTN occurrence. Patients whose IOP was elevated > 30% or ≥ 20 mmHg at 1 month post-implantation, subsequently developed OHTN with statistical significance. In conclusion, shorter axial length and younger age were associated with OHTN occurrence after IVD implantation. Additionally, identifying levels or trends in IOP at 1 month after the IVD procedure may be helpful in predicting subsequent OHTN occurrence.

Incidence and seasonality of major ocular trauma: a nationwide population-based study.

We designed this study to identify the epidemiological characteristics and trends of various types of ocular trauma in the population of the Republic of Korea. We conducted a nationwide, population-based, cross-sectional study using the Korean National Health Insurance claims database for January 2010 to December 2018. We compiled the monthly numbers of patients diagnosed with hyphema and those who received open reduction surgery due to orbital blowout fracture (BOF), primary closure of the cornea or sclera (PCCS), or intraocular foreign body (IOFB) removal. We obtained annual and monthly incidence rates, and differences according to age, sex, yearly trends, and seasonal variations. The incidence rate (per 100,000 person-years) was high in the order of hyphema (18.43), BOF (11.58), PCCS (1.99) and IOFB removal (0.39). Male predominance was evident in all types of major ocular trauma, but the age distribution varied with the type: hyphemas were most prevalent at 10-14 years of age, BOFs at 25-29 years of age, and open globe injuries (OGIs) at age 60 and older. Although all types of trauma showed significant seasonality, hyphemas (amplitude: 174.81) and BOFs (23.17) showed higher amplitudes compared to OGIs (PCCS: 11.96; IOFB removal: 6.72). While the incidence of blunt trauma injuries, including hyphemas and orbital BOFs, decreased steadily from 2010 to 2018, that of OGIs showed no remarkable change.