Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

AIMS/INTRODUCTION: Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. MATERIALS AND METHODS: In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. RESULTS: Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. CONCLUSIONS: The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Efficacy of Subtraction Computed Tomography Arteriography During Preoperative Embolization in Spinal Tumors.

Background: This study aimed to evaluate the efficacy of subtraction computed tomography arteriography (s-CTA) during preoperative embolization in spinal tumors. Methods: The study analyzed 17 vertebrae in 13 patients who underwent preoperative embolization before spinal fixation surgery for malignant spinal tumors to decrease blood loss at our hospital from 2019 to 2021. Their ages ranged from 56 to 88 years (average, 73.5 years). Metastatic bone tumors were most common, including five cases originating as lung carcinomas and three as renal cancers. After digital subtraction angiography of selected tumor-feeding arteries and non-subtraction CTA (ns-CTA) were performed, s-CTA was conducted using data obtained from both procedures. A clarity score of the boundary between the normal bone and tumor was derived for each patient, which was then classified into four grades (good, 3 points; fair, 2 points; faint, 1 point; poor, 0 points) by two experienced radiologists, followed by a comparison between the s-CTA and ns-CTA groups using the Wilcoxon signed-rank test. Results: Clarity scores were significantly higher in the s-CTA group than in the ns-CTA group (P < 0.001). The agreement of Cohen's coefficients between the two radiologists was κ = 0.724 in s-CTA scoring and κ = 0.622 in ns-CTA scoring, which were moderately matched. Seven arteries were not embolized due to insufficient tumor contrast enhancement and their poor relation to the surgical invasion zone. No complications were observed during or after embolization. Conclusion: S-CTA successfully distinguished between tumor and normal bone and may help avoid unnecessary embolization.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Efficacy and safety of transdermal electrical stimulation in patients with nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: No effective treatment for NAION with strong evidence has been established till date. The aim of this investigator-led, prospective, non-randomized, open-label, uncontrolled multi-center exploratory clinical trial is to evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with NAION. METHODS: Five patients with monocular NAION underwent TdES (10-ms biphasic pulses, 1.0 mA, 20 Hz, 30 min) of the affected eye six times at 2-week intervals. The primary endpoint was the logarithm of the mini-mum angle of resolution (logMAR) visual acuity at 12 weeks compared with 0 weeks. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, and mean deviation (MD) of the Humphrey field analyzer (HFA) 10-2 and HFA Esterman test scores. Additionally, the safety of TdES was evaluated. RESULTS: LogMAR visual acuity improved by ≥ 0.1 in two eyes, and ETDRS visual acu-ity improved by ≥ 5 characters in one eye. The mean change in logMAR visual acuity from week 0 showed an increasing trend. The mean MD of HFA 10-2 showed no obvious change, while HFA Esterman score improved in four eyes. All patients completed the study according to the protocol, and no treatment-related adverse events were observed. CONCLUSIONS: TdES treatment may have improved visual acuity and visual field in some patients. Further sham-controlled study in larger cohort is needed on its effectiveness. TRIAL REGISTRATION: UMIN, UMIN000036220. Registered 15 March, 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041261 .

Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization.

A continuous downstream process of monoclonal antibody was developed based on the process characterization. Periodic-counter current chromatography (PCCC) with two protein A columns was used for the capture step. For low pH virus inactivation (VI), a batch reactor was employed, which can work as a surge (buffer) tank. Flow-through chromatography (FTC) with two connected columns of different separation modes (anion-mixed mode and cation exchange) was designed as a polish step. After 24 h PCCC run, the collected pool was processed for VI. After adjusting pH and electric conductivity, the solution was fed to the two connected FTC columns for 24 h. Virus filter was also connected to the exit of the connected-column. PCCC and FTC were run in parallel. Six runs of different feed rates (0.5-10 L/day) and feed concentrations (1-3.2 g/L) were performed with protein A columns of 1-5 mL and FTC columns of 3-10 mL. The largest run (feed rate 10 L/day, feed concentration 2 g/L) was carried out at a GMP facility with 15 mL protein A columns and 100 mL FTC columns. Good recovery and purity values were obtained for all runs. The process was found to be flexible and stable for feed fluctuations. Only three surge or pool tanks were needed in addition to the final product pool tank.

A Pediatric Case of Extraneural Subcutaneous Metastasis of Ependymoma.

Ependymoma is the third most common brain tumor in children. Extracranial metastases of ependymomas are uncommon. A 21-month-old Japanese boy was diagnosed to be brain dead due to a posterior fossa (PF) brain tumor. Surgical resection of the tumor was not performed. Twenty-seven months later, he developed a truncal subcutaneous tumor, which was pathologically diagnosed as PF ependymoma group A. We observed the intracranial recurrence of the brain tumor, an invasion to the left orbit, and a neoplasm in his liver before he died. This case suggests that PF ependymoma group A can metastasize extracranially to various organs.

Percutaneous ethanolamine oleate sclerotherapy for aggressive vertebral hemangioma: A case report.

Vertebral hemangiomas are the most common benign lesion of the spine which are often an asymptomatic incidental finding. However, a few hemangiomas are aggressive and characterized by bone expansion and extraosseous extension into the paraspinal and epidural spaces. We report the case of a patient presenting an aggressive vertebral hemangioma causing back pain and bilateral numbness of the legs. Among various treatment modalities, a minimally invasive percutaneous sclerotherapy procedure using ethanolamine oleate under computed tomography and fluoroscopic guidance was safely and successfully performed with good clinical outcomes.

Viral clearance in end-to-end integrated continuous process for mAb purification: Total flow-through integrated polishing on two columns connected to virus filtration.

There are few reports of the adoption of continuous processes in bioproduction, particularly the implementation of end-to-end continuous or integrated processes, due to difficulties such as feed adjustment and incorporating virus filtration. Here, we propose an end-to-end integrated continuous process for a monoclonal antibody (mAb) with three integrated process segments: upstream production processes with pool-less direct connection, pooled low pH virus inactivation with pH control and a total flow-through integrated polishing process in which two columns were directly connected with a virus filter. The pooled virus inactivation step defines the batch, and high impurities reduction and mAb recovery were achieved for batches conducted in succession. Viral clearance tests also confirmed robust virus reduction for the flow-through two-column chromatography and the virus filtration steps. Additionally, viral clearance tests with two different hollow fiber virus filters operated at flux ranging from 1.5 to 40 LMH (liters per effective surface area of filter in square meters per hour) confirmed robust virus reduction over these ranges. Complete clearance with virus logarithmic reduction value ≥4 was achieved even with a process pause at the lowest flux. The end-to-end integrated continuous process proposed in this study is amenable to production processes, and the investigated virus filters have excellent applicability to continuous processes conducted at constant flux.

Economic Impacts and Quality of Life for Caregivers of Patients with Retinitis Pigmentosa: A Cross-Sectional Japanese Study.

Retinitis pigmentosa (RP) is the second leading cause of visual impairment in Japan and causes progressive vision loss in affected patients. Caregiving for patients with RP is associated with socioeconomic impacts; however, data on the magnitude and scope of these impacts are lacking. This cross-sectional study surveyed informal caregivers of patients with RP in Japan. The questionnaire assessed the socioeconomic status of participants; work impacts through the Work Productivity and Activity Impairment Questionnaire adapted for caregivers; and quality of life impacts through the Japanese version of the Caregiver Reaction Assessment (CRA) and the 5-level EQ-5D version (EQ-5D-5L). Of the 37 participating caregivers, 28 (75.7%) were employed. Among those, the average annual income was 2,722,080 yen (n = 20) and the mean loss of work productivity was 6.6%. The mean EQ-5D-5L index score was 0.882, and the mean CRA total score was 2.1. A mild to very severe impact on family life, leisure and hobbies, social life, and mental health was experienced by 83.8%, 78.4%, 75.7%, and 70.3%, respectively. These results suggest that caregivers of patients with RP may be disadvantaged in terms of employment and income and may experience wide-ranging impacts on their quality of daily life.

Quality of Life and Economic Impacts of Retinitis Pigmentosa on Japanese Patients: A Non-interventional Cross-sectional Study.

INTRODUCTION: Retinitis pigmentosa (RP) is an inherited progressive disease, characterized by a loss of photoreceptors, and is the second leading cause of visual impairment in Japan. RP is currently incurable and can result in complete blindness, with affected patients typically experiencing a gradual loss of light sensitivity, visual field, and visual acuity. Identification of any unmet medical needs of patients with this condition requires an understanding of the impacts of RP; in this study, we surveyed Japanese patients with RP to investigate the quality of life and economic impacts of visual impairment. METHODS: This non-interventional, cross-sectional study surveyed Japanese patients with RP. Economic impact was measured using an original questionnaire that assessed out-of-pocket cost (e.g., vision aids and medical services), salary gap with the general public, and the cost of depression and anxiety. Worker productivity was assessed using the Work Productivity and Activity Impairment Questionnaire (WPAI). Quality of life was evaluated using the Health Utilities Index Mark 3 (HUI3), the National Eye Institute Visual Function Questionnaire-25 (VFQ-25), and the 5-level EQ-5D version (EQ-5D-5L). The primary outcome was direct and indirect costs of visual impairment or blindness during the lifetime of patients with RP. RESULTS: Among 122 surveyed patients with RP, the estimated annual cost per patient was 218,520 yen (2176 USD), and the estimated lifetime cost per patient was 18,523,909 yen (184,501 USD). Additional robustness testing increased the estimated annual cost and lifetime cost per patient to 783,176 yen (7801 USD) and 66,389,827 yen (661,253 USD), respectively. In working patients, work productivity loss was 26.2% per person and impairment of daily activities was 31.6% per person. The mean VFQ-25, HUI3, and EQ-5D-5L scores were 42.0, 0.393, and 0.833, respectively. CONCLUSION: RP imposed a heavy economic burden and negative quality of life impacts in Japanese patients.

Exploratory clinical trial to evaluate the efficacy and safety of transdermal electrical stimulation in patients with central retinal artery occlusion.

PURPOSE: To evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO). METHODS: Five eyes of five patients with CRAO underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) six times at 2-week intervals. Only the affected eye was stimulated with 1.0-mA pulses in all patients. The primary endpoint was the best-corrected logMAR visual acuity. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, mean deviation of the Humphrey field analyzer (HFA) 10-2, and HFA Esterman test score. We also evaluated its safety. RESULTS: The logMAR visual acuity at 12 weeks was improved by 0.1 or more in two patients and was maintained in two patients compared to the baseline. No obvious changes in the mean logMAR visual acuity, ETDRS visual acuity, mean deviation, and HFA Esterman score were observed at 12 weeks compared to the baseline. All five enrolled patients completed the study according to the protocol. No treatment-related adverse events were observed during this study. CONCLUSION: In this study, logMAR visual acuity was slightly improved in two patients, confirming the safety of TdES. Since CRAO has no established treatment method, further research into the effects of TdES treatment in CRAO patients may be beneficial.

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing.

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

An accelerated approach for mechanistic model based prediction of linear gradient elution ion-exchange chromatography of proteins.

With growing demands for therapeutic monoclonal antibodies, in silico downstream process development based on mechanistic modeling of chromatography separation process is being increasingly used for process optimization and process characterization. Application of mechanistic modeling in biopharmaceutical industry has been sparse due to the significant investment of time and resources that are required for performing model calibration. Mechanistic modeling of the chromatography process involves a large number of mass transport and binding parameters and their initial input values are required for simulations. These input values of column parameters can be easily obtained either from experiments or from empirical correlations available in literature. On the other hand, obtaining the model input valves for binding kinetic parameters is usually a cumbersome process as it involves performing batch experiments which are not only tedious but also require significant quantities of purely isolated main product and its related impurities, which is challenging as the product related impurities are typically present in smaller quantities and hence are difficult to obtain as pure species. In the present work, a mechanistic model that is based on the general rate model coupled with extended Langmuir binding model has been used for prediction of linear gradient elution peaks of monoclonal antibody on cation exchanger chromatography. The present work describes an accelerated approach for obtaining the input values for binding kinetic parameters in the extended Langmuir binding model from the two Yamamoto coefficient A and B values obtained by Yamamoto method directly from the model calibration linear gradient elution runs of different gradient slopes and at low to moderate protein loadings. The equations that can relate the two coefficients to the extended Langmuir model equation binding kinetic parameters were derived. Therefore, once A and B are determined, the binding kinetic parameter values were determined straightforward, thereby avoiding the problem of multiple solutions for the model parameters. The estimated binding parameters were successfully validated from isocratic elution experiments performed at low loading. What we demonstrate is that the proposed approach allows us to estimate binding kinetic parameters in a significantly more efficient and accelerated manner than presently used approaches, thereby accelerating development and implementation of mechanistic modeling for process chromatography.

Progression Rate of Visual Function and Affecting Factors at Different Stages of Retinitis Pigmentosa.

We reviewed medical records of 121 patients/235 eyes of typical retinitis pigmentosa (RP) patients who could be followed up for at least 5 years with the aim of investigating the long-term course of visual function progression at each RP stage and appropriate assessment methods. Patients were classified into three groups: mild RP (baseline mean deviation (MD) ≥ -5), moderate RP (-25 < baseline MD < -5), and late RP (baseline MD ≤ -25). Linear mixed-effect models were used to follow MD, the average retinal sensitivity of the central four points of the Humphrey field analyzer 10-2 program (S4), and visual acuity (VA) with increasing time. The associations among factors (baseline MD group, sex, hereditary form) and the interaction between each factor and time were also investigated. The mean reduction of the MD, S4, and VA for all patients was -0.37 dB/year, -0.25 dB/year, and 0.018/year, respectively. The moderate RP group had a faster progression than other groups in MD (-0.43 dB/year, p < 0.05). The moderate (-0.31 dB/year, p = 0.01) and late RP groups (-0.25 dB/year, p < 0.01) had faster progression than the mild RP group in S4. The late RP group had faster progression in VA than the other groups (0.03/year, p < 0.05). Females had a slower progression of the S4 (-0.15 dB/year, p = 0.02) and VA (0.01/year, p < 0.001) than males. The autosomal dominant group had a slower progression than the sporadic group in MD (-0.22 dB/year, p = 0.02); the autosomal dominant and autosomal recessive groups had a slower VA decline than the sporadic group (0.01/year, p = 0.03; 0.01/year, p = 0.04). Because the progression rates of VA and visual field test differed as per the RP stage, S4 and VA can also be useful assessment methods depending on the stage. Inheritance form and sex may affect the progression rate.

Randomized clinical trial comparing intravitreal aflibercept combined with subthreshold laser to intravitreal aflibercept monotherapy for diabetic macular edema.

To compare the efficacy and safety of intravitreal aflibercept with three loading doses + pro re nata regimen combined with subthreshold laser application to that of IVA monotherapy on eyes with diabetic macular edema. This was a phase 4 clinical trial with a prospective, randomized, and parallel investigator-driven protocol. Patients with DME were randomly assigned to the IVA monotherapy group (n = 25) or the IVA + SL combination therapy group (n = 26). The main outcome measures were the number of IVA injections and the changes in the best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) at the final evaluation at 96 weeks. The mean number of IVA injections in the monotherapy group was 5.86 ± 2.43 and it was 6.05 ± 2.73 in the IVA + SL group at 96 weeks, and this difference was not significant (P = 0.83). The differences in the mean changes of the CRT (P = 0.17) and the BCVA (P = 0.31) were also not significant between the two groups throughout the follow-up period. We conclude that adjunct of SL to anti-VEGF therapy does not reduce the number of necessary intravitreal injections.

Sodium-Glucose Co-Transporter 2 Inhibitors Reduce Macular Edema in Patients with Diabetes mellitus.

PURPOSE: To determine the efficacy of systemic sodium-glucose co-transporter 2 inhibitors (SGLT2i) on diabetic macular edema (DME). METHODS: The medical records of patients with DME with a central retinal thickness (CRT) ≥320 µm in men and 305 µm in women, more than 6 months after the initiation of diabetes mellitus treatment, were reviewed. The CRT and best-corrected visual acuity (BCVA) were evaluated before and after the initiation of systemic SGLT2i and non-SGLT2i treatments. RESULTS: There were 24 eyes of 19 patients with DME that were treatment naïve or had not received treatments for the DME within four months before the initiation of SGLT2i. In these patients, the BCVA had a 0.31 ± 0.39 logarithm of the minimum angle of resolution (logMAR) units at the baseline, and it did not improve significantly at 0.26 ± 0.29 logMAR units after the initiation of SGLT2i (p = 0.56). However, the SGLT2i treatment significantly reduced the CRT from 423.3 ± 79.8 µm to 379.6 ± 69.5 µm (p = 0.0001). In the same evaluation of 19 eyes of 14 patients with DME that were initiated with non-SGLT2i agents, there was no significant difference between the baseline BCVA and the BCVA after the initiation of non-SGLT2i (p = 0.47). The CRT increased significantly after the initiation of non-SGLT2i (p = 0.0011). In three eyes in which the SGLT2i treatments were administered at the time of anti-vascular endothelial growth factor (VEGF) treatments, the anti-VEGF treatment alone had only a limited effect on the DME, but the reduction in the DME was enhanced after the addition of SGLT2i. CONCLUSIONS: These findings indicate that systemic SGLT2i can reduce DMEs, and they suggest that SGLT2i may be an additional treatment option to anti-VEGF treatments for eyes with DMEs.

Long-term follow-up of retinal morphology and physiology after 2000 mg sildenafil overdose as a means of attempted suicide: a case report.

BACKGROUND: Few case reports have described sildenafil overdose, particularly ingestion of > 1000 mg, and overdose-induced changes in visual function remain unclear. We report retinal morphology, retinal sensitivity, and findings of electrophysiological evaluation over long-term follow-up in a case of sildenafil overdose (2000 mg). CASE PRESENTATION: Our patient developed visual abnormalities in the paracentral visual field accompanied by photophobia, decreased contrast sensitivity, and difficulty distinguishing colors in both eyes, 8 hours after the sildenafil overdose. These symptoms did not improve throughout the course, and although abnormalities of retinal morphology and sensitivity, as well as the electroretinogram findings showed slight improvement, the patient did not recover completely at 6-month follow-up. CONCLUSIONS: We observed that high-dose sildenafil ingestion leads to retinal toxicity; the ocular abnormalities may persist for at least 6 months. Optical coherence tomography, Humphrey perimetry, microperimetry, and multifocal electroretinography are useful to quantitatively monitor temporal changes.

Evaluating the efficacy and safety of transdermal electrical stimulation on the visual functions of patients with retinitis pigmentosa: a clinical trial protocol for a prospective, multicentre, randomised, double-masked and sham-controlled design (ePICO trial).

INTRODUCTION: Previously, we conducted a clinical trial to evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes to improve the visual functions in patients with retinitis pigmentosa (RP). No adverse events were related to the treatment during follow-up examinations, and TdES significantly improved the mean visual acuity and visual field sensitivity. METHODS AND ANALYSIS: We developed a study protocol for a prospective, multicentre, randomised, double-masked and sham-controlled clinical trial, planned to commence on June 2021. We intend to compare the maintenance or improvement in best-corrected visual acuity, and safety of TdES using skin electrodes between patients with RP and the sham group. The primary endpoint comprises the superiority of the logarithm of the minimum angle of resolution (logMAR) visual acuity change at week 24 from baseline in the treatment and sham groups. Secondary endpoints involve the comparison of the treatment and sham groups at week 24 for the logMAR visual acuity, early treatment diabetic retinopathy study visual acuity, the mean deviation value of Humphrey field analyser 10-2, monocular Humphrey Esterman visual field test score, ellipsoid zone length, central foveal thickness and 25-item National Eye Institute Visual Function Questionnaire score. We intend to enrol 50 patients from three Japanese institutions within 1 year and follow them up for 1 years. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board at the Chiba University Hospital and two other institutions, and was registered with the Japan Registry of Clinical Trials on 17 May 2021. The trial will be conducted in accordance with the principles of the Declaration of Helsinki, and is in accordance with Good Clinical Practice standards. The findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: JRCT2032210094.

The relationship between behavioral problems and screen time in children during COVID-19 school closures in Japan.

BACKGROUND AND OBJECTIVES: Studies have shown that COVID-19 school closures negatively impacted children's well-being. We assessed the impact of school closures on children in Japan. We postulated that screen time and sleep habits during school closure would be associated with children's mental health status. METHODS: A cross-sectional study was conducted with 959 children in four public elementary schools. Parents completed an original questionnaire in which we enquired about children's behavioral problems, screen time (duration of watching TV/videos and duration of playing video games), sleep habits, and bodyweight change during school closure. Logistic regression analyses were performed to investigate the relationships between behavioral problems, bodyweight gain, and screen time. RESULTS: It was found that 50.3% of children exhibited some behavioral problems during school closure; fewer children exhibited such problems after schools reopened. Moreover, children's behavioral problems during school closure were associated with longer total screen time (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.14-1.28, p < .001). Sleep habits were not different between children with behavioral problems and those without. Of the children, 16.7% experienced bodyweight gain during school closure, which was associated with behavioral problems (OR: 2.0, 95% CI: 1.43-2.92, p < .001) and time spent watching TV/videos (OR: 1.2, 95% CI: 1.08-1.28, p < .001) during closure. CONCLUSIONS: COVID-19 school closure negatively impacted school children physically and psychologically. Screen time was associated with both physical and mental health status. Therefore, children should not engage in arbitrary screen time during school closures and should be supported in their daily routines.

CASE OF IDIOPATHIC UVEAL EFFUSION THAT DEVELOPED PROLIFERATIVE DIABETIC RETINOPATHY AFTER SCLERAL RESECTION SURGERY.

BACKGROUND/PURPOSE: To report a diabetic patient with uveal effusion that developed proliferative diabetic retinopathy after unsuccessful scleral resection for the uveal effusion. CASE REPORT: A 50-year-old Japanese man with nonproliferative diabetic retinopathy and uveal effusion in his right eye underwent partial thickness sclerectomies at the four quadrants to treat the uveal effusion. These procedures reduced the amount of subretinal fluid and thus the choroidal and retinal detachment. However, the retinal detachment recurred and proliferative diabetic retinopathy developed with pre- and subretinal proliferation at 5 months after the surgery. The patient then underwent pars plana vitrectomy combined with phacoemulsification and implantation of an intraocular lens. During the surgery, the vasoproliferative membrane was removed, panretinal photocoagulation was performed, and intraocular tamponade with silicone oil was performed. After the removal of the silicone oil, the retina remained attached but the visual acuity was 2/20 because of macular atrophy. CONCLUSION: Clinicians should be aware that treatment of a uveal effusion by scleral resection can lead to a progression of nonproliferative diabetic retinopathy to proliferative diabetic retinopathy.