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Nicotinamide adenine dinucleotide regulates various biological processes. Nicotinamide mononucleotide (NMN) increases its intracellular levels and counteracts age-associated changes in animal models. We investigated the safety and efficacy of oral nicotinamide mononucleotide supplementation in older patients with diabetes and impaired physical performance.We carried out a 24-week placebo-controlled, double-blinded study of male patients with diabetes aged ≥65 years with reduced grip strength (26 kg) or walking speed (1.0 m/s). The primary end-points were to determine the safety of NMN oral administration (250 mg/day), and changes in grip strength and walking speed. The secondary end-points were to determine the changes in various exploratory indicators.We studied 14 participants aged 81.1 ± 6.4 years. NMN was tolerable without any severe adverse events. The changes in grip strength and walking speed showed no difference between the two groups: 1.25 kg (95% confidence interval -2.31 to 4.81) and 0.033 m/s (-0.021 to 0.087) in the NMN group, and -0.44 kg (-4.15 to 3.26) and 0.014 m/s (-0.16 to -0.13) in the placebo group, respectively. There were no significant differences in any exploratory indicators between the two groups. However, improved prevalence of frailty in the NMN group (P = 0.066) and different changes in central retinal thickness between the two groups (P = 0.051) was observed.In older male patients with diabetes and impaired physical performance, NMN supplementation for 24 weeks was safe, but did not improve grip strength and walking speed. Geriatr Gerontol Int 2022; ••: ••-••.

We present a case of a congenital retinal macrovessel (CRM) with spontaneous resolution of cystoid macular edema. A 39-year-old woman with sudden decreased vision in her right eye was referred to our clinic and found to have a CRM with macular edema. Her visual acuity was 20/25. A week later, the macular edema disappeared without any treatment, and her visual acuity was 20/15. We performed optical coherence tomography angiography and fluorescein angiography (FA), which revealed no obstruction of retinal flow but a slight disturbance of retinal flow near the central fovea on FA. We encountered a case of spontaneous resolution of macular edema with abnormal vessel crossing near the central macula by a CRM, and multimodal imaging was useful for investigating the pathology of the disease.

Purpose To quantitatively and morphologically document enlarged neovascularization elsewhere (NVE) using widefield swept-source (SS) optical coherence tomography angiography (OCTA) with vitreoretinal interface (VRI) slab images. Design Retrospective observational imaging study. Participants The study included 46 NVEs in 25 eyes of 21 consecutive patients who presented with severe proliferative diabetic retinopathy with NVEs between March 2018 and June 2020 at Osaka University Hospital. Methods All patients underwent ophthalmologic examinations, including ultra-widefield fluorescein angiography (UWF-FA) imaging and widefield SS-OCTA scans. Main outcome measures We evaluated the area and the vascular density (VD) of NVEs detected on five 12×12 mm2 or two 15×9 mm2 SS-OCTA panoramic VRI slab images taken at the first and final visits. Results At baseline, the mean area of the NVEs on OCTA was 1.85 ±2.81 mm2, and the vascular density of the NVEs was 73.9 ± 14.6%. At the final visit, the mean area of the NVEs on OCTA was 2.14 ± 3.14 mm2, and the mean vascular density of the NVEs was 65.3 ± 17.1%. The average NVE size change (mm2/month) was significantly associated with the ischemic index (P=0.009). NVE growth could be classified into two patterns: round-shaped (61.8%) and ramified (38.2%). The round-shaped group tended to have a larger ischemic index at baseline than the ramified group (p=0.0375). Conclusions We quantified the size and density of NVEs over time. The NVE size increase was significantly associated with the severity of ischemic changes. Furthermore, the ramified growth pattern was significantly correlated with the ischemic index. These findings suggest that the morphology of NVE is associated with more severe ischemia.

Background During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. Methods We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-μm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. Results In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. Conclusions Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.

Purpose Our previous 1-year pilot study evaluated the efficacy of intravitreally injected activated protein C (APC) in 10 eyes with ischemic central retinal vein occlusion (CRVO). The reperfusion of the areas of retinal nonperfusion (RNP) exceeded 50% of the baseline in five (50%) eyes 1 year after the APC injection. The current study evaluated the long-term efficacy and safety of intravitreal APC. Methods The 10 eyes in the pilot study were included in this study. Other treatments were administered at the physicians’ discretion after the pilot study. We evaluated visual acuity (VA), central retinal thickness (CRT) and perfusion status, and adverse events and severity over the long term. Results The median follow-up was 60 months (range, 48–68 months). Compared with baseline, the post-treatment VA improved significantly (P P Conclusion No complications were associated with intravitreal APC, the clinical course improved, and improved RNP was maintained for the long term, suggesting that intravitreal APC may be an alternative treatment for CRVO.

To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV).We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months.The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (RIntravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

PurposeThe endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.MethodsThis study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.ResultsTwo SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities.ConclusionThis study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.

Purpose To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. Methods Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. Results Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p Conclusion The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P

Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found a-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and a-synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.

To compare the choroidal neovascularization (CNV) flow patterns and the relationship between perforating vessels (PVs) and CNV in the three different stages of networks in myopic CNV (mCNV) using swept-source optical coherence tomography angiography (SS-OCTA). This retrospective study included 28 eyes with mCNV that was divided into three phases (active, scar, and atrophic) and observed by SS-OCTA. SS-OCTA findings, with special focus on the relationship between the PVs and CNV, were compared among the three phases. Overall, the CNV signal was detected in 31 of the 34 areas of CNV (91%); in the active, scar, and atrophic phases, respectively, CNV signals were detected in eight of eight areas of CNV (100%), 10 of 11 areas of CNV (91%), and 13 of 15 areas of CNV (86%). Two signal patterns were observed in each phase, i.e., dense and loop; in the atrophic phase, seven eyes were unclassifiable. The ratio between the dense and loop patterns did not differ significantly among the phases. In 30 of 34 areas of CNV for which clear images were obtained, the PVs and CNV were connected directly or indirectly in 19 area of CNV, and in five areas of CNV, trunk-like vessels were connected to the PVs within the CNV. The numbers of foveal or parafoveal CNVs accompanied by PVs were significantly (p=0.0048) greater than those of the extrafoveal CNV. OCTA provides detailed observation of mCNV and the relationship between CNV and PVs. Although the CNV signal pattern does not differ depending on the degree of atrophy, there are cases in which only the trunk-like vessels connect to the PVs within the CNV in the atrophic phase without CNV flow signal.

To examine the associations between the disorganization of the retinal inner layers (DRIL) and optical coherence tomography angiography characteristics and visual acuity (VA) outcomes in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). In this single-center cross-sectional cohort study, the data of 43 patients with macular edema secondary to BRVO that received pro re nata anti-vascular endothelial growth factor therapy were analyzed. B-scan and en face angiographic images were obtained by swept-source-based wide-field optical coherence tomography angiography performed at a single visit 1 month after the anti-vascular endothelial growth factor therapy session and evaluated. Correlations between the vascular indices in macula-centered 3 × 3 and 12 × 12 mm2 areas and B-scan parameters, such as DRIL length and VA, were examined. The mean DRIL length (Rs = 0.588, p

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient&rsquo, s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity.Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined.After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm in the SCP and 3.25 ± 0.91 mm in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm in the SCP and 1.78 ± 1.73 mm in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P0.001) and with smaller SCP and DCP foveal avascular zone areas (both P0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P0.05) and ischemia (determined via pretreatment fluorescein angiography, P0.05), and positively correlated with photoreceptor integrity (P0.001).Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

PurposeTo investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD).DesignRetrospective, interventional, consecutive case series.MethodsThree hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm.ResultsNineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 non-responders.ConclusionIntravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability.

Purpose The purpose of this study was to quantify choroidal vessels (CVs) in pathological eyes in three dimensions (3D) using optical coherence tomography (OCT) and a deep-learning analysis. Methods A single-center retrospective study including 34 eyes of 34 patients (7 women and 27 men) with treatment-naïve central serous chorioretinopathy (CSC) and 33 eyes of 17 patients (7 women and 10 men) with Vogt-Koyanagi-Harada disease (VKH) or sympathetic ophthalmitis (SO) were imaged consecutively between October 2012 and May 2019 with a swept source OCT. Seventy-seven eyes of 39 age-matched volunteers (26 women and 13 men) with no sign of ocular pathology were imaged for comparison. Deep-learning-based image enhancement pipeline enabled CV segmentation and visualization in 3D, after which quantitative vessel volume maps were acquired to compare normal and diseased eyes and to track the clinical course of eyes in the disease group. Region-based vessel volumes and vessel indices were utilized for disease diagnosis. Results OCT-based CV volume maps disclose regional CV changes in patients with CSC, VKH, or SO. Three metrics, (i) choroidal volume, (ii) CV volume, and (iii) CV index, exhibit high sensitivity and specificity in discriminating pathological choroids from healthy ones. Conclusions The deep-learning analysis of OCT images described here provides a 3D visualization of the choroid, and allows quantification of features in the datasets to identify choroidal disease and distinguish between different diseases. Translational Relevance This novel analysis can be applied retrospectively to existing OCT datasets, and it represents a significant advance toward the automated diagnosis of choroidal pathologies based on observations and quantifications of the vasculature.

Purpose: This study aimed to assess driving capabilities in patients with exudative age-related macular degeneration (AMD) causing unilateral blindness or paracentral scotoma without vision deterioration. Methods: Of the 275 patients with AMD who responded to a questionnaire regarding car driving at Osaka University Hospital, we excluded 78 patients who answered that they had never driven. Finally, 197 patients were included (50 with bilateral and 142 with unilateral AMD). We investigated the relationship between the questionnaire findings and best-corrected visual acuity (BCVA). Results: The mean age was 74.8 ± 6.9 years, and the mean BCVA in the right and left eyes were 0.48 and 0.47, respectively. A negative correlation was observed between the proportion of patients who stopped driving due to AMD and the vision in the worse eye (p &lt, 0.0001), however, 66% of participants were still driving. Regardless of the BCVA, 84% of them wished to continue driving. Concerning perceived dangerous situations, all patients reported an oversight of people or signals and night driving, further, patients with unilateral and bilateral vision deterioration reported vision narrowness and difficulty with discerning signal colours, respectively. Conclusion: Despite the associated danger, patients with AMD continued driving. Close attention should be paid to the driving activities among patients with AMD, even if they have passed the relevant driving tests.

The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of theThis study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs inTwo SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; IThis study revealed

At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis. Three hundred thirteen eyes (313 patients) with treatment-naive AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 μm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained. Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes. Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.

PURPOSE To evaluate the visual function of patients with cornea verticillata associated with Fabry disease through quantitative evaluations of contrast sensitivity function and straylight. METHODS We enrolled 28 eyes of 14 patients with Fabry disease (mean age, 37.1 ± 17.2 years) and 20 eyes of 20 age-matched healthy controls. Comprehensive ophthalmological examinations were performed and contrast sensitivity and letter contrast sensitivity were measured for all patients, following which the area under the log contrast sensitivity function (AULCSF) was calculated. Straylight was quantified using a straylight metre. Furthermore, subgroup analysis was performed according to the whorl-like pattern of cornea verticillata (mild and typical groups). RESULTS All 28 eyes showed cornea verticillata. Visual acuity and letter contrast sensitivity values were the same for normal eyes and those with Fabry disease. AULCSF differed by 0.15 log[s] between the eyes with Fabry disease and the control eyes (p

Purpose To establish geometrically based methods for simulating panretinal laser photocoagulation (PRP) for the photocoagulation index. Methods A formula for calculating the curved surface area of a spherical dome was used for the simulation. If the radius of the dome is c and the height of the dome is h, then the curved surface area (S) of the dome is S = π (c2 + h2). We calculated the area of the whole retina using this formula and the anatomical dimensions of the standard eyeball. To simulate PRP with a 400-μm spot on the retina with 1-spot spacing, we drew 400-μm-diameter circles, separated by 400 μm, on a retinal map. We calculated the ratio of the total retinal photocoagulated area to the whole retina, termed the photocoagulation index, in order to investigate the impact of the extent of the photocoagulated area and the pulse duration on PRP. Results The whole retinal area was 1,092 mm2. The numbers of spots in the scattered and full-scattered PRP were 1,222 and 1,814, respectively. The photocoagulation index was 14.1% and 20.9% for scattered and full-scattered PRP, respectively. These values changed to 14.3% (5.6%) and 21.3% (8.3%), respectively, for PRP with a 100-ms pulse or a 20-ms pulse. Conclusions This method will be useful for investigating the impact of various PRP parameters (duration, spacing, intensity of burns, extent of photocoagulated area, etc.) on the photocoagulation index.

Diagnostic biomarkers for amyotrophic lateral sclerosis (ALS) have yet to be identified. One of the causes of neuronal cell death in neurodegenerative diseases is abnormal RNA metabolism, although the mechanisms by which this occurs are unclear. Detection of abnormal RNA metabolism in white blood cells (WBCs) could lead to a new biomarker of ALS onset. TAR DNA-binding protein 43kDa (TDP-43) is an RNA-binding protein that regulates RNA metabolism. We previously developed a mouse model of ALS that exhibits adult-onset motor dysfunction; these mutant TDP-43 knock in (KI) mice heterozygously express mutant human TDP-43 (A382T or G348C). In the present study, we examined TDP-43 mRNA levels in WBCs of KI mice and found that A382T mutant mRNA is significantly higher than G348C. Our results suggest that each mutant TDP-43 induces distinct RNA metabolism, and that the expression of total TDP-43 alone in WBC is not suitable as an ALS biomarker. To identify additional candidates, we focused on survival and apoptosis-related factors and examined their mRNA metabolism in WBCs. mRNA levels of both Smn1 and Naip5 correlated with TDP-43 levels and also differed between A382T and G348C. Together, TDP-43 and these factors may enable detection of abnormalities in individual ALS pathologies.

We investigated changes in retinal vascular area and the foveal avascular zone (FAZ) after intravitreal aflibercept in diabetic macular edema (DME) and the association of these changes with visual outcomes. The retinal vascular area in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) and the FAZ area were measured using optical coherence tomography angiography (OCTA) in 23 eyes of 23 patients with DME, before and after intravitreal aflibercept. Overall, there was no significant change in retinal vascular area or FAZ. Better BCVA after treatment was significantly associated with larger retinal vascular area in the SCP and the DCP, both at baseline (R2 = 0.512, P 2 = 0.361, P = 0.002, respectively) and after intravitreal aflibercept (R2 = 0.717, P 2 = 0.618, P

Purpose To characterize wide-field optical coherence tomography angiography (OCTA) features of retinal nonperfusion in eyes with branch retinal vein occlusion (BRVO). Methods Automated scanning of five 12 × 12-mm areas of swept-source OCTA and wide-field fluorescein angiography (FA) images was performed in a consecutive case series of 27 eyes in 27 patients with BRVO in this institutional cross-sectional study. The correlation between the areas of retinal nonperfusion detected by both examinations was assessed. Panoramic images obtained in five 12 × 12-mm OCTA scans in eyes with retinal nonperfusion were binarized or skeletonized, and the associations between vascular parameters such as vascular density (VD) and vascular length (VL) with the wide-field FA characteristics were evaluated. Results The mean area of retinal nonperfusion in the OCTA images was 81.0 ± 66.8 mm2 (range, 0.0-188.8). The mean areas of retinal nonperfusion in FA and the total FA images were, respectively, 84.7 ± 72.5 mm2 (range, 0.0-221.9) and 184.1 ± 167.7 mm2 (range, 0.0-515.0). The mean VD was 27.6 ± 3.5% (range, 19.6-33.7), and the mean VL was 12.4 ± 8.5% (range, 5.4-31.3). Separate regression analyses of the areas of retinal nonperfusion in FA (p = 0.0004, R2 = 0.4627) and the total FA (p = 0.0008, R2 = 0.4214) images showed a significant association with the VL. Conclusions OCTA images based on wide-field technologies can quantitatively evaluate retinal nonperfusion in eyes with BRVO.