Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

PURPOSE: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. STUDY DESIGN: A descriptive study involving four confirmed LHON patients. METHODS: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. RESULTS: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. CONCLUSION: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation.

Impact of drainage retinotomy on surgical outcomes of retinal detachment: insights from the Japan-Retinal Detachment Registry.

We investigated the impact of drainage retinotomy on the outcome of pars plana vitrectomy for repair of rhegmatogenous retinal detachment (RRD). This study was a retrospective observational multicenter study. All patients were registered with the Japan-Retinal Detachment Registry. We analyzed 1887 eyes with RRD that had undergone vitrectomy and were observed for 6 months between February 2016 and March 2017. We compared the baseline characteristics and postoperative outcomes between eyes with and without drainage retinectomy. We then performed propensity score matching using preoperative findings as covariates to adjust for relevant confounders. Of 3446 eyes, 1887 met the inclusion criteria. Among them, 559 eyes underwent vitrectomy with drainage retinotomy, and 1328 eyes underwent vitrectomy without drainage retinotomy. After propensity score matching, each group comprised 544 eyes. There was no significant difference between the two groups in BCVA at 6 months after vitrectomy (0.181 vs. 0.166, P = 0.23), the primary anatomical success rate (6.3% vs. 4.4%, P = 0.22), or the rate of secondary surgery for ERM within 6 months (1.5% vs. 1.3%, P = 1.0). Drainage retinectomy does not increase the risk of decreased postoperative BCVA, surgical failure, or secondary surgery for ERM within six months outcomes.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Macular hole and vitreous hemorrhage subsequent to stereotactic hypofractionated radiotherapy for choroidal melanoma: A case report and review of the literature.

Choroidal melanoma is the leading primary intraocular tumor with potentially fatal outcomes in adults. The coexistence of choroidal melanoma and a macular hole is extremely rare, and treatment strategies and information on the prognosis of associated complications are currently lacking. We report the first case of choroidal melanoma complicated with a macular hole and vitreous hemorrhage after stereotactic hypofractionated radiotherapy in Japan, and review the relevant literature in relation to the possible mechanisms, treatment strategies, and outcomes. An 83-year-old male with choroidal melanoma was treated with stereotactic hypofractionated radiotherapy in January 2021. Five months later, a full-thickness macular hole developed, followed by an acute massive vitreous hemorrhage about 2 weeks later. Following confirmation of tumor regression, the patient underwent a pars plana vitrectomy and internal limiting membrane peeling. The macular hole was closed postoperatively and the patient's best-corrected visual acuity improved to 20/125. There was no evidence of intraocular tumor dissemination or distant metastases during follow-up. A systematic literature search only identified 10 previous cases of choroidal melanoma with a macular hole in eight reports worldwide, mainly in females. Macular edema may be the primary cause of macular hole formation in these cases. Most patients who underwent vitrectomy for complications after tumor regression achieved a good prognosis. The development of a macular hole is a rare complication associated with choroidal melanoma. Anterior-posterior traction of posterior vitreous detachment and secondary macular edema may have contributed to the formation of the macular hole in the current case.

Incidence of Leber hereditary optic neuropathy in 2019 in Japan: a second nationwide questionnaire survey.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an acute or subacute optic neuropathy that mainly affects young males. The first nationwide epidemiological survey of LHON was conducted in 2014 in Japan, and LHON was officially designated as a rare intractable disease by the Japanese government in 2015. We conducted a second survey of the annual incidence of LHON in 2019, and estimated the total number of patients with LHON in Japan. RESULTS: A questionnaire was sent to 997 facilities accredited by the Japanese Ophthalmological Society and/or affiliated with the councilors of the Japanese Neuro-Ophthalmology Society. Responses were received from 791 facilities, with a response rate of 79%. Fifty-five newly diagnosed cases (49 males and 6 females) of LHON were reported from 35 institutions in 2019, with a median age of 28.5 for males and 49.5 years for females. The total number of newly diagnosed cases was calculated as 69 (62 were males and 7 were females, 95% confidence interval 55-83), and the total number of patients was estimated to be 2491 (95% confidence interval: 1996-2986), suggesting a prevalence of LHON in Japan of 1:50,000. CONCLUSION: The incidence of LHON in 2019 was lower than the estimate in 2014, whereas its prevalence may be similar to that reported in other countries. The accurate estimation of the incidence and prevalence of patients with LHON requires prospective registration.

Correction: Sugimoto et al. Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan. J. Clin. Med. 2022, 11, 165.

In the original publication [...].

Autotuning of Vibrational Strong Coupling for Site-Selective Reactions.

Site-selective chemistry opens new paths for the synthesis of technologically important molecules. When a reactant is placed inside a Fabry-Perot (FP) cavity, energy exchange between molecular vibrations and resonant cavity photons results in vibrational strong coupling (VSC). VSC has recently been implicated in modified chemical reactivity at specific reactive sites. However, as a reaction proceeds inside an FP cavity, the refractive index of the reaction solution changes, detuning the cavity mode away from the vibrational mode and weakening the VSC effect. Here we overcome this issue, developing actuatable FP cavities to allow automated tuning of cavity mode energy to maintain maximized VSC during a reaction. As an example, the site-selective reaction of the aldehyde over the ketone in 4-acetylbenzaldehyde is achieved by automated cavity tuning to maintain optimal VSC of the ketone carbonyl stretch during the reaction. A nearly 50 % improvement in site-selective reactivity is observed compared to an FP cavity with static mirrors, demonstrating the utility of actuatable FP cavities as microreactors for organic chemistry.

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.

Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion: Multicenter Study in Japan.

PURPOSE: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. METHODS: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients' baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. RESULTS: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = -0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (ß = 0.191, p < 0.001) and the right eye (ß = -0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. CONCLUSIONS: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.

Selective crystallization via vibrational strong coupling.

The coupling of (photo)chemical processes to optical cavity vacuum fields is an emerging method for modulating molecular and material properties. Recent reports have shown that strong coupling of the vibrational modes of solvents to cavity vacuum fields can influence the chemical reaction kinetics of dissolved solutes. This suggests that vibrational strong coupling might also effect other important solution-based processes, such as crystallization from solution. Here we test this hitherto unexplored notion, investigating pseudopolymorphism in the crystallization from water of ZIF metal-organic frameworks inside optical microcavities. We find that ZIF-8 crystals are selectively obtained from solution inside optical microcavities, where the OH stretching vibration of water is strongly coupled to cavity vacuum fields, whereas mixtures of ZIF-8 and ZIF-L are obtained otherwise. Moreover, ZIF crystallization is accelerated by solvent vibrational strong coupling. This work suggests that cavity vacuum fields might become a tool for materials synthesis, biasing molecular self-assembly and driving macroscopic material outcomes.

Clinical Characteristics and Outcomes in 314 Japanese Patients with Bacterial Endophthalmitis: A Multicenter Cohort Study from J-CREST.

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.

Neoadjuvant Hyperthermia and Chemoradiotherapy for Borderline Resectable Pancreatic Cancer.

Pancreatic cancer(PC)is associated with poor prognosis and low resectability rates. Currently, only 15-20% of all patients are candidates for upfront surgery at the time of diagnosis, which offers the chance of long-term survival. In recent years, patients with borderline resectable PC(BR-PC)have been treated with surgery following neoadjuvant chemoradiotherapy or intensive multi-agent chemotherapy. In PC, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of chemo(radio)therapy. An 84-year-old man with fatty stool was diagnosed with pancreatic head cancer according to the result of contrast computed tomography(CT), which showed a 37 mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric artery(SMA)plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was BR-PC, cT3, N0, M0, cStage Ⅱ A. The patient was treated with hyperthermia plus S-1 and radiotherapy. The size of the tumor had reduced from 37 mm to 15 mm after the neoadjuvant therapy, and the infiltration into the SMA plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)concomitant resection of the PV, SMV, SV confluence. The histopathological findings were invasive ductal carcinoma with R0 radical resection. There has been no recurrence 18 months after the surgery. Based on the above-mentioned findings, hyperthermia and chemoradiotherapy can be an effective option of neoadjuvant treatment for BR-PC.

Successful nonoperative management by endoscopic and percutaneous drainage for penetrating pancreatic duct injury: a case report.

BACKGROUND: Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage. CASE PRESENTATION: A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged. CONCLUSIONS: Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

Conventional Trabeculotomy versus Gonioscopy-Assisted Transluminal Trabeculotomy: A Retrospective Cohort Study.

BACKGROUND: Conventional trabeculotomy (CT) is performed in an ab-externo manner with at most 120 degrees of incision area of Schlemm's canal (SC). Recently, gonioscopy-assisted transluminal trabeculotomy (GATT), which makes possible a 360-degree incision area of SC in an ab-interno manner, is introduced. The purpose of this study was to compare surgical outcomes for CT and GATT with and without simultaneous phacoemulsification over 24 months and to identify factors associated with surgical success. RESULTS: Patients' baseline characteristics were not significantly different between two groups. The surgical success rate in CT and GATT with phacoemulsification groups were 40.4% and 96.6% and were significantly higher in the GATT group than in the CT group (p < 0.001). However, the surgical success rate in CT and GATT without phacoemulsification groups were 40.8% and 54.2%, and there were no significant differences between two groups without phacoemulsification (p = 0.55). Similarly, the postoperative IOP was significantly lower in the GATT group than in the CT group only in eyes with simultaneous phacoemulsification. There were no significant differences in the numbers of glaucoma medications between the two groups. Additional glaucoma surgery was needed in 13.2% and 25.9% of patients in the GATT and CT groups, respectively (p = 0.157). The multivariate logistic regression analysis revealed that the surgical success of trabeculotomy was significantly associated with combined phacoemulsification and the type of glaucoma surgery (GATT). CONCLUSION: Although both groups without phacoemulsification had a similar surgical success and IOP-lowering effect, GATT combined with phacoemulsification had a higher surgical success rate and a greater IOP-lowering effect compared with combined CT and phacoemulsification. Multivariate logistic regression analysis showed that the factors associated with higher surgical success at one year and two years postoperatively were the combined phacoemulsification procedure and the GATT.

Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.