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Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.

We investigated the relationship between pachydrusen and choroidal thickness and age in eyes with polypoidal choroidal vasculopathy (PCV) and fellow eyes, compared to eyes with central serous chorioretinopathy (CSC). This retrospective study included 89 eyes with PCV and 146 eyes with CSC. The number, location, and shape of the pachydrusen and their association with choroidal thickness and age were analyzed. PCV eyes showed pachydrusen more frequently than eyes with CSC (52% vs. 20%, p < 0.001). Large solitary type and clustered type were more frequent in PCV eyes compared to CSC eyes (p = 0.003 and p = 0.001, respectively). Subfoveal choroidal thickness was associated with pachydrusen in eyes with PCV (odds ratio [OR] 1.006, 95% confidence interval [CI] 1.001–1.011, p = 0.027), while age was associated with pachydrusen in CSC eyes (OR 1.137, 95% CI, 1.073–1.205; p < 0.001). Pachydrusen were localized directly over the pachyvessel on optical coherence tomographic findings in approximately two thirds of PCV eyes and fellow eyes (62% and 67%, respectively). Risk factors for pachydrusen differ according to diseases. The presence of pachydrusen was associated with choroidal thickness in PCV, while the association with age was more prominent in CSC.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.

Background/AimsTo analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum.MethodsThis study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed.ResultsFifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS.ConclusionPatients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.

Introduction There are only a few studies on the clinical utility of filler injections for penile augmentation (PA) in patients with small penis syndrome (SPS), which is a type of anxiety or body dysmorphic disorder, not a true micropenis. Aim To compare the clinical outcomes of hyaluronic acid (HA) with polylactic acid (PLA) filler injection for temporary PA in patients with SPS. Methods Our prospective, patient/evaluator-blind, comparative, randomized, non-inferiority trial consisted of a single filler injection and a 24-week post-injection period. Seventy-four men with SPS were included between November 2017 and February 2018. Patients were divided into those injected with HA (n = 39) and those injected with PLA filler (n = 35). Main Outcome Measure The psychological effects of PA, based on the Beliefs about Penis Size Scale, penile girth, and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks post-injection. Results At 24 weeks, the mean penile girth increases were 2.1 ± 1.0 cm (P < .001) in the HA group and 1.6 ± 0.9 cm (P < .001) in the PLA group, with a mean difference of 0.5 ± 0.2 cm between groups (P = .031). In both groups, satisfaction levels significantly increased at 24 weeks, with 1.8 ± 1.7 and 1.6 ± 1.4 mean increases in the visual analog scale for penile appearance satisfaction in the HA and PLA groups, respectively (each P < .001), and 1.0 ± 1.1 and 0.7 ± 1.2 mean increases in the visual analog scale for sexual life satisfaction in the HA and PLA groups, respectively (each P < .001), with no significant differences between groups (P = .950 and P = .287). The mean Beliefs about Penis Size Scale scores significantly decreased at 24 weeks, with 7.8 ± 8.3 and 5.3 ± 7.2 mean decreases in the HA and PLA groups, respectively (each P < .001), and no significant difference between the groups (P = .920). There were no serious adverse events, but filler injection-related adverse events in the HA and the PLA groups were reported in 2 cases (5.13%) and 5 cases (14.29%), respectively (P = .245). Clinical Implications Our study provides an overview of clinical course after HA and PLA filler injections for PA and suggests that filler injections can be considered an alternative approach in patients with SPS. Strengths & Limitations Our study is the first to assess the psychological symptoms in patients with SPS who received the filler injection for PA; however, the follow-up duration was insufficient to prove the long-term outcomes of fillers. Conclusion Without serious adverse events, HA and PLA filler injections for PA significantly resulted in not only an augmentative effect but also improvement of psychological distress, and the clinical utility was comparable between the fillers.

Post-micturition dribble (PMD) is the involuntary loss of urine immediately after urination. It is classified as a post-micturition symptom and is more common in males. Traditionally, PMD has been considered to be part of the aging process, to have a low prevalence, and to be less bothersome than other lower urinary tract symptoms (LUTS). However, recent evidence suggests that PMD is not less common and does not elicit less discomfort compared with other LUTS in males. Also, PMD seems to commonly overlap with other LUTS and to be associated with erectile dysfunction. Although the etiology of PMD is not fully understood, a weakness or failure of the pelvic floor muscles is considered to be the most important factor. Although bulbar urethral massage and pelvic floor exercises are known to be effective in treating PMD, pharmacologic treatment has not yet been introduced. Recently, the possibility of treating PMD with phosphodiesterase-5 inhibitor has been suggested.

We aimed to determine the upper and lower cutoff values to simplify the diagnosis of gestational diabetes mellitus (GDM). We investigated the 50-g oral glucose tolerance test (OGTT) results from 1441 pregnancies and identified 423 gravidas who underwent the 100-g OGTT from 2011 to 2019. We collected the results of 50- and 100-g OGTTs. Moreover, we obtained the sum of the 50-g OGTT and 0-hour values, and the sum of those levels and 1-hour values. We determined the upper cutoff at 50-g OGTT, 0-, 1-hour, sum of 50-g OGTT and 0-hour results, and sum of those levels and 1-hour results for the confirmation of GDM. Also, we determined the lower cutoff at these tests for the exclusion of GDM. The upper cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 222, 115, 212, and 315 mg/dL, respectively. The lower cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 131, 65, 151, and 208 mg/dL, respectively. In addition, we discovered that the upper and lower cutoffs in the sum of 50-g OGTT, 0- and 1-hour values were516 and373 mg/dL, respectively. We implemented these cutoffs to our study group at 50-g OGTT and 0-, 1-hour of 100-g OGTT. It could omit 2- and 3-hour sampling in 216 gravidas (51.1%). Our approach was able to simplify GDM diagnostic steps in half of our study group.

PurposeTo compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study.DesignHAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration.MethodsOf the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96.ResultsMean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept.ConclusionIn Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.

PurposeTo develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti–vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment.DesignClinical study evaluating diagnostic accuracy.ParticipantsPatients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments.MethodsIn phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN).Main Outcome MeasuresSensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA.ResultsIn eyes with persistent activity, the combination of 3 non–ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN.ConclusionsIn nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.

PurposeTo evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.MethodsThis retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.ResultsForty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.ConclusionNon-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

Survival analyses for malignancies, including renal cell carcinoma (RCC), have primarily been conducted using the Cox proportional hazards (CPH) model. We compared the random survival forest (RSF) and DeepSurv models with the CPH model to predict recurrence-free survival (RFS) and cancer-specific survival (CSS) in non-metastatic clear cell RCC (nm-cRCC) patients. Our cohort included 2139 nm-cRCC patients who underwent curative-intent surgery at six Korean institutions between 2000 and 2014. The data of two largest hospitals’ patients were assigned into the training and validation dataset, and the data of the remaining hospitals were assigned into the external validation dataset. The performance of the RSF and DeepSurv models was compared with that of CPH using Harrel’s C-index. During the follow-up, recurrence and cancer-specific deaths were recorded in 190 (12.7%) and 108 (7.0%) patients, respectively, in the training-dataset. Harrel’s C-indices for RFS in the test-dataset were 0.794, 0.789, and 0.802 for CPH, RSF, and DeepSurv, respectively. Harrel’s C-indices for CSS in the test-dataset were 0.831, 0.790, and 0.834 for CPH, RSF, and DeepSurv, respectively. In predicting RFS and CSS in nm-cRCC patients, the performance of DeepSurv was superior to that of CPH and RSF. In no distant time, deep learning-based survival predictions may be useful in RCC patients.

Pachychoroid is characterized by dilated Haller vessels and choriocapillaris attenuation that are seen on optical coherence tomography (OCT) B-scans. This study investigated the feasibility of using deep learning (DL) models to classify pachychoroid and non-pachychoroid eyes from OCT B-scan images. In total, 1898 OCT B-scan images were collected from eyes with macular diseases. Images were labeled as pachychoroid or non-pachychoroid based on strict quantitative and qualitative criteria for multimodal imaging analysis by two retina specialists. DL models were trained (80%) and validated (20%) using pretrained convolutional neural networks (CNNs). Model performance was assessed using an independent test set of 50 non-pachychoroid and 50 pachychoroid images. The final accuracy of AlexNet and VGG-16 was 57.52% for both models. ResNet50, Inception-v3, Inception-ResNet-v2, and Xception showed a final accuracy of 96.31%, 95.25%, 93.40%, and 92.61%, respectively, for the validation set. These models demonstrated accuracy on an independent test set of 78.00%, 86.00%, 90.00%, and 92.00%, and an F1 score of 0.718, 0.841, 0.894, and 0.920, respectively. DL models classified pachychoroid and non-pachychoroid images with good performance. Accurate classification can be achieved using CNN models with deep rather than shallow neural networks.

To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings.Evaluation of diagnostic test results.Panel of retina specialists.As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts.Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD.The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%.We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

AimsAutomatic identification of pachychoroid maybe used as an adjunctive method to confirm the condition and be of help in treatment for macular diseases. This study investigated the feasibility of classifying pachychoroid disease on ultra-widefield indocyanine green angiography (UWF ICGA) images using an automated machine-learning platform.MethodsTwo models were trained with a set including 783 UWF ICGA images of patients with pachychoroid (n=376) and non-pachychoroid (n=349) diseases using the AutoML Vision (Google). Pachychoroid was confirmed using quantitative and qualitative choroidal morphology on multimodal imaging by two retina specialists. Model 1 used the original and Model 2 used images of the left eye horizontally flipped to the orientation of the right eye to increase accuracy by equalising the mirror image of the right eye and left eye. The performances were compared with those of human experts.ResultsIn total, 284, 279 and 220 images of central serous chorioretinopathy, polypoidal choroidal vasculopathy and neovascular age-related maculopathy were included. The precision and recall were 87.84% and 87.84% for Model 1 and 89.19% and 89.19% for Model 2, which were comparable to the results of the retinal specialists (90.91% and 95.24%) and superior to those of ophthalmic residents (68.18% and 92.50%).ConclusionsAuto machine-learning platform can be used in the classification of pachychoroid on UWF ICGA images after careful consideration for pachychoroid definition and limitation of the platform including unstable performance on the medical image.

PURPOSE: To investigate outcomes of combined photodynamic therapy (PDT) and intravitreal bevacizumab in association with choroidal morphology in polypoidal choroidal vasculopathy (PCV). METHOD: Eighty-six PCV eyes (83 patients) treated with PDT in combination with intravitreal bevacizumab and followed for 1 year were evaluated. Choroidal morphological features including subfoveal choroidal thicknesses, diameter of pachyvessel, and choroidal vascularity were analyzed for association with responsiveness and recurrence. RESULT: Total choroid, Haller’s layer, and pachyvessel were thicker in responders (n = 70) compared with non-responders (n = 16) at baseline (298 vs. 227 μm, 213 vs. 144 μm, and 276 vs. 210 μm, respectively; all P ≤ 0.001). Choroidal vascularity was significantly higher (0.68 vs 0.60, P

The aim of the present study was to evaluate the efficacy of the inverted internal limiting membrane (ILM) flap technique that involved the use of a perfluorocarbon liquid (PFCL) bubble for the selective prevention of indocyanine green (ICG) staining of the parts of the inverted flap in contact with the retinal pigment epithelium for large macular hole (MH) closure.This retrospective, interventional, comparative study included 26 patients with idiopathic large MHs (minimum diameter, 400 µm) who underwent vitrectomy using the inverted ILM flap technique with conventional ILM staining with ICG (n = 14, Group 1) or PFCL-mediated selective ILM staining with ICG (n = 12, Group 2). The hole closure rate, best-corrected visual acuity (BCVA), and optical coherence tomography findings were analyzed at baseline and 1, 3, and 6 months after surgery in both groups.Hole closure was achieved in all the eyes. BCVA significantly improved after surgery in both groups (p 0.001 for both groups), although Group 2 exhibited significantly better values at 3 and 6 months after surgery (p = 0.008 and 0.001 at 3 and 6 months, respectively). The sizes of ellipsoid zone defect significantly decreased after surgery in both groups (p 0.001 relative to the baseline width in both groups), and it was significantly smaller in Group 2 than in Group 1 at 3 (p = 0.006) and 6 (p = 0.001) months after surgery.The findings of this study suggest that recovery of the photoreceptor layers and, consequently, the postoperative VA are better with the inverted ILM flap technique employing PFCL-mediated selective ILM staining with ICG than with the technique employing conventional ILM staining with ICG methods for patients with large MHs.

To compare choroidal vascular characteristics of age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC) by qualitative and quantitative analyses using swept-source en face optical coherence tomographic (OCT) images. Eyes with non-neovascular AMD (n = 32), neovascular AMD (n = 30), thick and thin choroid PCV (n = 33 and 27), and CSC (n = 34) were enrolled. Subfoveal choroidal thickness (SFCT) and the presence and patterns of pachyvessels were assessed. En face images of the large choroidal vessel layer were converted to binary images for the analysis of vascular density. Pachyvessels were identified in 8 (25%), 14 (46%), 28 (85%), 26 (96%), and 34 (100%) non-neovascular AMD, neovascular AMD, thin choroid PCV, thick choroid PCV, and CSC eyes, respectively (P

To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity.Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes.The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common.Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

BACKGROUND AND OBJECTIVE: To evaluate the retinal morphologic characteristics of patients with macropsia caused by epiretinal membrane (ERM) based on spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: A cross-sectional, non-interventional study was performed to compare the characteristics of retinal structures in eyes with ERM according to the presence or absence of macropsia. Twenty-six patients with ERM and macropsia were defined as the macropsia group and 26 age-matched patients with ERM without macropsia were the control group. All participants underwent a full ophthalmologic examination and SD-OCT examination. Macropsia was diagnosed and quantified using a double dot chart. The thickness of retinal layers, including the outer nuclear layer (ONL) and inner segment / outer segment / retinal pigment epithelium (IS/OS/RPE) at the central fovea, were measured by electronic calipers of the SD-OCT system. The interocular ratio of each parameter was calculated for each patient and compared between the two groups. The integrity of the external limiting membrane (ELM), IS/OS junction, and cone outer segment tips (COST) line were evaluated. RESULTS: The thickness of the IS/OS/RPE differed significantly between both eyes in the macropsia group ( P < .001), whereas the control group was not significantly different ( P = .161). The ONL in the diseased eye was significantly thicker in the macropsia group than in the control group ( P = .020), whereas these two groups did not differ significantly in the thickness of ONL in the control eye ( P = .860). More patients had a disrupted COST line in the macropsia group ( P < .001 for macropsia group, P = .252 for control group). No eye showed disrupted ELM and IS/OS junction, regardless of the presence of macropsia. CONCLUSIONS: Eyes with macropsia showed thicker foveal ONL, IS/OS/RPE, and more frequently disrupted COST lines. This may indicate that the contractile strength of ERM can lead to centralization of photoreceptor cells. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:656–663.]

We compared the outcomes of SWL to treat distal ureter stones with regard to the conventional prone and supine positions using the transgluteal approach through the greater sciatic foramen. A prospective, randomized, single-blind, and multicenter study was conducted between October 2014 and July 2015. The inclusion criteria were radio-opaque distal ureter stones with a maximum diameter of 0.5−2 cm as measured on a CT scan. The included 160 patients were randomly assigned to two groups: the prone group (n = 80; treated in the conventional prone position) and the transgluteal group (n = 80; treated in the supine position using a transgluteal approach). In the latter group, the focused shock wave was transmitted through the greater sciatic foramen with the head positioned at a 40° angle to the vertical. “Stone-free” was defined as the complete clearance of stone fragments, assessed using a CT scan at 2 weeks after treatment. Overall satisfaction was self-reported using a 0–5 Likert scale. The overall efficacy was 66.9%. The stone-free rate was significantly higher in the transgluteal group (72.6%) than in the prone group (54.7%; odds ratio 2.413, 95% CI 1.010−5.761, P = 0.023). No serious adverse events due to treatment were observed in either group. The satisfaction score of the transgluteal group was 4.21 ± 0.81, and 83.6% were willing to repeat the same procedure if necessary. SWL using the transgluteal approach via a supine position through the greater sciatic foramen was more effective than via the conventional prone position. Furthermore, this approach provided a comparably safe and satisfactory procedure.

Purpose To investigate vascular endothelial growth factor (VEGF) level according to the clinical and imaging features, and to explore its relationship with the responsiveness to anti-VEGF treatment in eyes with polypoidal choroidal vasculopathy. Methods Aqueous samples were collected from 62 eyes of 62 patients with treatment-naive polypoidal choroidal vasculopathy. Vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay. Baseline best-corrected visual acuity, central macular thickness, subfoveal choroidal thickness, greatest linear dimension of the lesion, and the presence of hemorrhage were included in the analysis. The effects of 3 monthly intravitreal ranibizumab injections on best-corrected visual acuity and central macular thickness were assessed. Results Baseline VEGF level was negatively correlated with subfoveal choroidal thickness (r = -0.33, P = 0.01). Other variables had no correlation with VEGF level. The mean change in central macular thickness after anti-VEGF treatment was -51 ± 64 μm, which is positively correlated with VEGF concentration (r = 0.30, P = 0.04) and negatively correlated with subfoveal choroidal thickness (r = -0.35, P = 0.02). Conclusion Vascular endothelial growth factor level demonstrated a negative correlation with baseline subfoveal choroidal thickness and was associated with response to anti-VEGF treatment. These findings suggest that VEGF has a variable contribution to the pathogenesis of polypoidal choroidal vasculopathy depending on choroid thickness.

Polylactic acid (PLA) fillers are widely used for cosmetic volume augmentation. But, no study has evaluated the use of PLA filler in penile augmentation (PA No. 4). We evaluated the efficacy and safety of a newly developed PLA filler for PA during a 18-month follow-up period. A total of 23 healthy adult men were prospectively enrolled between June and November 2012. Penile girth was measured at proximal-, mid- and distal-shaft at baseline, 3, 6, 12 and 18 months following injection. Subjects' satisfaction was assessed with visual analogue scale (VAS). Adverse events (AEs) were also reported. Mean injected volume was 20 ml. The circumference of proximal-, mid-, and distal-shaft increased by a mean of 2.2±0.2, 2.7±1.0 and 2.7±1.0 cm at 3 months, respectively (each P0.001). No significant differences were noted in girth circumference between 3 and 18 months post-injection (each P0.05). VAS score increased from 51.6±14.7 at baseline to 64.8±19.3 and 74.3±14.6 at 3 and 6 months, respectively (each P0.05). Six cases of mild, transient treatment-emergent AEs were reported in 5 subjects. Serious AEs were not reported. In conclusion, penile injection of a newly developed PLA filler led to significant penile augmentative effects for up to 18 months and was well tolerated without serious AEs.

Purpose To determine the impact of choroidal vascular morphology on clinical outcomes in patients with polypoidal choroidal vasculopathy/aneurysmal Type 1 neovascularization. Methods Sixty-six eyes with polypoidal choroidal vasculopathy/aneurysmal Type 1 were included. Eyes were subdivided according to the choroidal vascular morphology of the large vessel layer on optical coherence tomography en face images: focal (n = 39) versus diffuse (n = 27) pachyvessels. All patients were treated with intravitreal ranibizumab pro re nata with or without rescue photodynamic therapy. Results Best-corrected visual acuity at baseline, 6, and 12 months did not differ between groups (P = 0.394, 0.142, and 0.292). At Month 3, best-corrected visual acuity was worse, and the proportion of eyes with fluid was higher in the focal group (P = 0.016 and 0.024). Among responders, the number of injections during 12-month follow-up was higher in the focal group (P = 0.033). During the total follow-up period, photodynamic therapy was required in 15 eyes (10 focal and 5 diffuse group, P = 0.497). The injection-free period after the photodynamic therapy was shorter in the focal group (P = 0.018). Conclusion The polypoidal choroidal vasculopathy/aneurysmal Type 1 eyes with a diffuse pattern of pachyvessels required fewer injections during 12-month follow-up and showed a longer injection-free period after rescue photodynamic therapy.

To compare the effects of taking tadalafil 5 mg and placebo once daily on post-micturition dribble (PMD) in men with lower urinary tract symptoms (LUTS).Our prospective, randomized, double-blind, placebo-controlled, multicentre trial enrolled 102 men with PMD and other LUTS. PMD was assessed using the Hallym Post-Micturition Dribble Questionnaire (HPMDQ) and according to PMD volume. Over a 12-week period, patients took either tadalafil 5 mg (n = 51) or placebo (n = 51) once daily and their HPMDQ and PMD volume results were evaluated. Adverse events (AEs) were also reported.Over the course of 12 weeks, total HPMDQscores and PMD volumes improved significantly more in the tadalafil group than in the placebo group (reduction of total HPMDQ score of ≥2 points in the tadalafil and placebo group in 68.8% and 31.9% of patients (P0.001) and decreased mean PMD volume in the tadalafil and placebo group at 0.48 mL and 0.22 mL, respectively (P = 0.046). Specifically, PMD frequency decreased and quality of life increased significantly more in the tadalafil group than in the placebo group (P = 0.029 and P0.001, respectively). Furthermore, 66.7% of the tadalafil group reported moderate and significant PMD improvement, whereas only 4.2% reported that tadalafil was ineffective. Treatment-emergent AEs did not significantly differ between the groups (all P0.05), and no serious AEs were observed.Taking tadalafil 5 mg once daily reduced PMD symptom severity and PMD volume in men with PMD, without inducing serious AEs, more effectively than placebo, suggesting that taking tadalafil 5 mg once daily may be an effective and well-tolerated PMD treatment.

To analyze features of the choriocapillaris in eyes with earlier stages of pachychoroid spectrum, this study included 46 eyes with PPE, 32 age-matched eyes with pachychoroid without epitheliopathy, and 30 normal controls. Macular 3 × 3 mm2 angiographic images were obtained with swept-source optical coherence tomography. Vascular density and signal void area in the choriocapillaris were analyzed. Topographical correlation of signal voids with the dilated choroidal large vessel (pachyvessel) was assessed. Choriocapillaris vascular density was significantly lower in eyes with PPE compared with controls (p = 0.003). The number, the total area and the average size of signal voids was the highest in the PPE group followed by the pachychoroid without epitheliopathy and then controls (all p ≤ 0.001). 89.0% signal void area colocalized with pachyvessels. The average size of the signal void was higher if it was colocalized with pachyvessel (p

To describe the clinical characteristics and courses for eyes with retinoschisis associated with pachychoroid. A retrospective interventional case series study. Twenty-one eyes (18 patients) with pachychoroid that showed retinoschisis without evidence of neovascularization that had been followed for 1 year were included. Multimodal imaging, including fundus photography, spectral-domain optical coherence tomography (OCT) with an enhanced depth protocol, fluorescein angiography (FA), and indocyanine green angiography (ICGA), was provided and treatment outcomes were analyzed. Focal RPE atrophy was present below or adjacent to the schisis in all eyes, and the mean atrophy area was 1.38 ± 1.37 mm2. Intraretinal fluids of the schisis originated from the atrophy area and involved the retinal layer which was correlated with the extent of outer retinal defect. Dilated Haller layer vessel and choroidal vascular hyperpermeability were observed under the area with atrophy in all eyes. After 1 year of treatment, 11 eyes (52%) still had fluid and 7 of them had fluid at the macula. Nonetheless, the mean central macular thickness decreased (144.4 to 121.8, P

Postmicturition dribbling (PMD) is a stressful symptom in middle-aged men characterized by urinary leakage after the completion of normal voiding. Appropriate treatments have not yet been introduced. This study assessed the efficacy of treatment of PMD with 75 mg udenafil daily.The study included 138 men with regular sexual lifestyles. The Hallym PMD questionnaire (HPMDQ) was used to assess PMD symptoms. After all basic examinations, patients were randomly assigned to either udenafil or placebo. Patients completed the surveys, uroflowmetry (UFM), a bladder scan, and the paper test during the follow-up visit.The mean age of the patients was 57.6 years. PMD with one of every three urinations was experienced by 59 patients (42.8%), whereas 45 patients (32.6%) experienced PMD with two of every three urinations. PMD with every urination was experienced by 34 patients (24.6%). More than half of the patients (89 patients, 65.4%) indicated that persistent PMD symptoms would likely result in moderate to severe discomfort in their daily activities. As time passed, the udenafil group showed significant improvement in PMD symptoms (Udenafil 75 mg once daily can be an effective treatment for patients with PMD symptoms.

Background Limited data exist on real-world treatment patterns for diabetic macular edema (DME) in Korea. In this study, we investigated DME treatment patterns from 2009 to 2014 and the impact of baseline treatment on healthcare resource utilization and visual acuity (VA) outcomes. Methods A retrospective cohort chart review of DME patients treated at 11 hospital ophthalmology clinics between January 1, 2012 and December 31, 2013 was conducted. We collected data on demographics, healthcare resource utilization (clinic visits, treatment visits, and visits for ocular investigations), distribution of DME treatments, and VA. Results Overall, 522 DME patients (men, 55.2%; mean age, 59 years; mean HbA1c [n = 209], 8.4%) with 842 DME eyes were evaluated. For all treatments, healthcare resource utilization was significantly higher during the first 6 months versus months 7–12, year 2, or year 3 (P ≤ 0.001), but was highest for patients whose first treatment was an anti-vascular endothelial growth factor (VEGF) treatment (visits/quarter; anti-VEGF, 1.9; corticosteroids, 1.7; laser, 1.4). Use of macular laser therapy decreased (44% to 8%), whereas use of anti-VEGF injections increased (44% to 69%) during the study period. However, VA improvement was not commensurate with healthcare resource utilization of anti-VEGF treatment (mean VA gain, 2.7 letters). Conclusion A trend toward increasing use of intravitreal anti-VEGF injections for DME treatment was observed in Korea. However, the frequency of dosing and monitoring was lower in clinical practice versus major clinical trials, which may have led to the less-than-favorable improvements in visual outcomes., Graphical Abstract

Purpose To study the efficacy of deep convolutional neural networks (DCNNs) to differentiate pachychoroid from nonpachychoroid on en face optical coherence tomography (OCT) images at the large choroidal vessel. Methods En face OCT images were collected from eyes with neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous chorioretinopathy. All images were prelabeled pachychoroid or nonpachychoroid based on quantitative and qualitative criteria for choroidal morphology on multimodal imaging by two retina specialists. In total, 1188 nonpachychoroid and 884 pachychoroid images were used for training (80%) and validation (20%). Accuracy for identification of pachychoroid by DCNN models was analyzed. Trained models were tested on a test set containing 79 nonpachychoroid and 93 pachychoroid images. Results The accuracy on the validation set was 94.1%, 93.2%, 94.7%, and 94.4% in DenseNet, GoogLeNet, ResNet50, and Inception-v3, respectively. On a test set, each model demonstrated accuracy of 80.2%, 83.1%, 89.5%, and 90.1% and an F1 score of 0.782, 0.824, 0.904, and 0.901, respectively. Conclusions DCNN models could classify pachychoroid and nonpachychoroid with good performance on OCT en face images. Automated classification of pachychoroid will be useful for tailored treatment of individual patients with exudative maculopathy. Translational Relevance En face OCT images can be used by DCNN for classification of pachychoroid.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

PURPOSE To subsegment the choroid in patients with polypoidal choroidal vasculopathy and to determine whether the ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness is decreased at sites of polypoidal pathology. METHODS Retrospective, observational, cross-sectional study. A total of 320 eyes of 305 patients with polypoidal choroidal vasculopathy were studied with optical coherence tomography and dye angiography. The ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness was calculated at polypoidal lesion sites in eyes with subfoveal choroidal thickness (SFCT) ≤200 μm. RESULTS Mean SFCT was 267.7 ± 118.5 μm for the entire cohort. Mean SFCT was 151.2 ± 35.0 μm in eyes with SFCT ≤200 μm (n = 124, 39%). In this subgroup, dilated Haller vessels (pachyvessels) were identified under the site of neovascular ingrowth in 117 eyes (94%). Choroidal thickness in the pachyvessel zone was greater (213.3 ± 52.2 μm) than SFCT (P < 0.001) with a significantly lower choriocapillaris/Sattler layer to total thickness ratio (P < 0.001). Qualitative alterations of the retinal pigment epithelium were observed in 60 eyes (51%). CONCLUSION Eyes with normal or subnormal SFCT exhibited extrafoveal choroidal thickening at sites of polypoidal disease. The choriocapillaris and Sattler layers were attenuated at these locations, but Haller vessels were markedly dilated. These changes were topographically associated with sites of neovascular ingrowth and support the classification of polypoidal choroidal vasculopathy as a pachychoroid disorder.

Purpose To describe the findings of enhanced depth imaging (EDI) optical coherence tomography (OCT) of the lamina cribrosa (LC) in glaucoma and pachychoroid spectrum diseases associated with peripapillary retinoschisis. Design Retrospective, observational case series. Participants A total of 16 patients from 1 institution. Methods Detailed medical case histories, optic disc and retinal imaging with EDI using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and clinical course were reviewed for patients with peripapillary retinoschisis without a known predisposing condition. Main Outcome Measures Clinical features and findings of the EDI OCT. Results Among the 16 eyes with peripapillary retinoschisis that had abnormal findings on EDI of the LC, 8 had glaucoma and 8 had pachychoroid spectrum diseases, including chronic central serous chorioretinopathy (CSC) (6 eyes), small pigment epithelium detachment (1 eye), and polypoidal choroidal vasculopathy (PCV) (1 eye). The abnormal LC findings were central or peripheral focal LC defects in eyes with glaucoma and LC disinsertions or peripheral focal LC defects in eyes with pachychoroid spectrum diseases. Central LC defects were related to inner layer retinoschisis, whereas LC disinsertions and peripheral LC defects were related to outer layer retinoschisis. The peripapillary retinoschisis did not show a topographic association with the underlying chronic CSC- or PCV-associated lesions. In 6 treated eyes with pachychoroid, peripapillary retinoschisis resolved along with subretinal fluid after anti–vascular endothelial growth factor injection in 4 eyes, whereas retinoschisis persisted after the resolution of subretinal fluid in 2 eyes. Conclusions Enhanced depth imaging OCT of the LC demonstrated alterations associated with peripapillary retinoschisis, pachychoroid spectrum diseases, and glaucoma.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people globally. It is estimated that there will be more Asians with AMD than the rest of the world combined by 2050. In Asian populations, polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative AMD, while choroidal neovascularization secondary to AMD (CNV-AMD) is the typical subtype in Western populations. The two subtypes share many common clinical features and risk factors, but also have different epidemiological and clinical characteristics, natural history and treatment outcomes that point to distinct pathophysiological processes. Recent research in the fields of genetics, proteomics and imaging has provided further clarification of differences between PCV and CNV-AMD. Importantly, these differences have manifested as disparity in response to intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) treatment between PCV and CNV-AMD, emphasizing the need for accurate diagnosis of PCV and in distinguishing PCV from CNV-AMD, particularly in Asian patients. Current clinical trials of intravitreal anti-VEGF therapy and photodynamic therapy will provide clearer perspectives of evidence-based management of PCV and may lead to paradigm shifts in therapeutic strategies away from those currently employed in the treatment of CNV-AMD. Further research is needed to clarify the relative contribution of specific pathways in inflammation, complement activation, extracellular matrix dysregulation, lipid metabolism and angiogenesis to the pathogenesis of PCV. Findings from this research, together with improved diagnostic technology and new therapeutics, will facilitate more optimal management of Asian AMD.

To evaluate the 1-year results of adjunctive photodynamic therapy in patients with Type 1 neovascularization associated with thickened choroid who were refractory to anti-vascular endothelial growth factor monotherapy.Data on 28 eyes of 28 patients with Type 1 neovascularization with a minimum subfoveal choroidal thickness of 300 μm were reviewed. All showed persistent subretinal and/or intraretinal fluid after at least 4 anti-vascular endothelial growth factor injections in the 6 months before adjunctive photodynamic therapy. No eyes had certain polypoidal lesions on indocyanine green angiography.At 3 months, complete fluid absorption was observed in 24 eyes (85.7%). The mean best-corrected visual acuity significantly improved (20/53-20/44, P = 0.040) and mean subfoveal choroidal thickness reduced (386 to 350 μm, P0.001) compared with baseline. Over a 1-year follow-up period, 17 eyes (60.7%) were free from recurrent fluid accumulation. Anti-vascular endothelial growth factor injection was mainly used in retreatment (mean: 1.5). At 12 months, best-corrected visual acuity improved by ≥0.3 logMAR or maintained compared with baseline in 27 eyes (96.4%).Adjunctive photodynamic therapy in eyes with Type 1 neovascularization with thickened choroid that were refractory to anti-vascular endothelial growth factor monotherapy resulted in complete fluid absorption in most eyes, which translated to visual improvement until 1 year.

Because diabetic retinopathy increases fracture risk, we studied the association between bone mineral density (BMD) and diabetic retinopathy in a nationally representative sample. A significant association between the presence of diabetic retinopathy and low BMD was observed. Therefore, diabetic retinopathy might be considered as a marker of low BMD. Several diabetic complications, including nephropathy, retinopathy, and peripheral neuropathy, are associated with a higher fracture risk in diabetic subjects. However, in contrast to diabetic nephropathy and peripheral neuropathy, which are associated with low bone mineral density (BMD), little is known about the association between BMD and diabetic retinopathy. The aim of the present study was to determine whether the prevalence of diabetic retinopathy is associated with BMD. This cross-sectional study included a nationally representative sample consisting of 4357 men aged 50 years and older and 4392 postmenopausal women who participated in the Korea National Health and Nutritional Examination Survey (KNHANES) from 2008 to 2011 and underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) and diabetic retinopathy assessments using seven standard gradable photographs. The diabetic women with retinopathy had lower mean BMD at all measured sites than those without retinopathy, although the BMD difference between the two groups was small (3–5 %). In addition, the diabetic women with retinopathy were 2.27 times more likely to have osteoporosis following adjustments for all clinically relevant covariates. However, the prevalence of diabetes mellitus (DM) or diabetic retinopathy was not associated with the prevalence of osteoporosis in men. This study has shown that the presence of diabetic retinopathy is significantly associated with a reduced BMD and increased prevalence of osteoporosis in diabetic women.

Background. The prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in nonmetastatic renal cell carcinoma (non-mRCC) is controversial, although NLR has been established as a prognostic factor in several cancers. The objective of our study was to assess the prognostic significance of preoperative NLR in non-mRCC, based on a large, multicenter cohort analysis. Methods. Totally, 1,284 non-mRCC patients undergoing surgery were enrolled from six institutions between 2000 and 2014. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were calculated, and the prognostic significance of NLR was evaluated. Results. Patients with higher NLR had larger tumors (p<0.001), higher T stage (p<0.001), worse Eastern Cooperative Oncology Group performance status (p<0.001), worse symptoms (p=0.003), sarcomatoid differentiation (p=0.004), and tumor necrosis (p<0.001). The 5-year RFS and CSS rates were significantly lower in patients with high NLR than in those with low NLR (each p<0.001). Multivariate analysis identified NLR to be an independent predictor of RFS and CSS (each p<0.05). Moreover, predictive accuracy of multivariate models for RFS and CSS increased by 2.2% and 4.2%, respectively, with NLR inclusion. Conclusions. Higher NLR was associated with worse clinical behavior of non-mRCC. Also, NLR was a significant prognostic factor of both RFS and CSS.

The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment.The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.ClinicalTrials.gov Identifier: NCT01846273.

PURPOSE. To evaluate the depth and pattern of retinal hemorrhage in acute central retinal vein occlusion (CRVO) and to correlate these with visual and anatomic outcomes. METHODS. Retinal hemorrhages were evaluated with color fundus photography and fluorescein angiography at baseline and follow-up. Snellen visual acuity (VA), central foveal thickness (CFT), extent of retinal ischemia, and development of neovascularization were analyzed. RESULTS. 108 eyes from 108 patients were evaluated. Mean age was 63.6 ± 16.1 years with a predilection for the right eye (73.1%). Average follow-up was 17.2 ± 19.2 months. Mean VA at baseline was 20/126 and 20/80 at final follow-up. Baseline (P = 0.005) and final VA (P = 0.02) in eyes with perivascular nerve fiber layer (NFL) hemorrhages were significantly worse than in eyes with deep hemorrhages alone. Baseline CFT was greater in the group with perivascular hemorrhages (826 ± 394 μm) compared to the group with deep hemorrhages alone (455 ± 273 μm, P < 0.001). The 10 disc areas of retinal ischemia was more common in patients with perivascular (80.0%) and peripapillary (31.3%) versus deep hemorrhages alone (16.1%, P < 0.001). Neovascularization of the iris was more common, although this differrence was not significant, in the groups with peripapillary (14.3%) and perivascular (2.0%) NFL versus deep hemorrhages alone (0.0%). CONCLUSIONS. NFL retinal hemorrhages at baseline correlate with more severe forms of CRVO, with greater macular edema, poorer visual outcomes, and greater risk of ischemia and neovascularization. This may be related to the organization of the retinal capillary plexus. The depth and pattern of distribution of retinal hemorrhages in CRVO may provide an easily identifiable early biomarker of CRVO prognosis.

Purpose We sought to evaluate longer-term efficacy and safety of intravitreal aflibercept monotherapy (IAI) vs IAI plus rescue photodynamic therapy (rPDT) in patients with polypoidal choroidal vasculopathy (PCV). Design This was a prospective multicenter, double-masked, sham-controlled randomized clinical study across 62 centers. Methods In this phase 3b/4 study, patients with PCV with best-corrected visual acuity of 73–24 Early Treatment Diabetic Retinopathy Study letters (20/40–20/320 Snellen equivalent) received IAI 2 mg every 4 weeks until week 12, when they were randomized 1:1 to receive IAI or IAI plus rPDT if rescue criteria were met. Patients not requiring rescue received IAI every 8 weeks; those requiring rescue received IAI every 4 weeks plus sham/active PDT. At week 52 (the primary endpoint), IAI was noninferior to IAI plus rPDT. After week 52, treatment intervals could be extended beyond 8 weeks at the investigators' discretion. Noninferiority of IAI vs IAI plus rPDT for mean best-corrected visual acuity change from baseline to week 96 was evaluated. Results Over 96 weeks, 54 patients (17.0%) met rescue criteria. At week 96, IAI was noninferior to IAI plus rPDT in terms of Early Treatment Diabetic Retinopathy Study letters gained (+10.7 vs +9.1, P = .48). Proportions of patients with complete polyp regression (33.1% vs 29.1%) or without active polyps (82.1% vs 85.6%) were similar. In year 2, the mean number of injections was 4.6 in both arms. No new safety signals were observed. Conclusion IAI monotherapy was noninferior to IAI with rescue PDT up to 96 weeks, and functional and anatomical improvements achieved at 52 weeks were maintained. Few patients required rescue PDT, which provided no additional visual benefit.

Background Studies about the clinical utility of fillers on penile augmentation (PA) are lacking. Furthermore, no randomized study has compared the utilities of fillers. Aim To compare the efficacy and safety between hyaluronic acid (HA) and polylactic acid (PLA) filler injection for PA. Methods This prospective, randomized patient/evaluator-blind, comparative multicenter study consisted of an initial 2-week baseline period and 48-week patient/evaluator-blind post-injection period. 72 patients with small penis syndrome were enrolled from 3 institutions between March–July 2016. Patients were divided into 2 groups: the HA group, comprising 36 patients injected with HA, and the PLA group, comprising 36 patients injected with PLA. Main Outcome Measures Penile girth and satisfaction were assessed at baseline and at 4, 12, 24, and 48 weeks after injection. Results Penile girth increases adequately lasted ≤48 weeks in both groups (16.95 ± 10.53 and 13.49 ± 9.98 mm of mean increase in the HA and PLA groups, respectively; P < .001). The mean penile girth increase in the HA group was significantly greater than that in the PLA group at 4 weeks (P < .001). Subsequently, it gradually decreased and was no longer significantly different at 48 weeks (P = .075). Satisfaction levels increased after injection and were maintained ≤48 weeks. No significant differences were observed in the overall satisfaction level between the groups (P > .05). Filler injection–related adverse events were mild and transient and occurred in 1 and 3 patients in the HA and PLA groups, respectively. Clinical Implications This study provides an overview of the efficacy and safety of HA and PLA fillers, which are the most commonly used soft tissue fillers for PA. Strength and Limitations This study, to our knowledge, is the first to compare the efficacy and safety between different filler injections for human PA. However, it was impossible to perform a researcher-blinded trial because of the unique properties of fillers, and 31 patients (43.1%) were dropped during the study period. Conclusions Both HA and PLA filler injections for PA led to a significant augmentative effect without serious adverse events and had clinically comparable efficacy and safety.

Purpose: To compare the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) combination therapy to single-agent antibiotic therapy for the resolution of symptoms during two restricted activity days in patients with acute uncomplicated cystitis (AUC)Materials and Methods: We performed a prospective, randomized control pilot study. A total of 55 patients were enrolled. Group I (n=28) was treated with cepodoxime (100 mg twice per day), and Group II (n=27) was treated with cepodoxime (100 mg) and aceclofenac (100 mg) twice per day; both groups were treated for three days. Upon dysuria after each administration, the participants entered a value on a numerical pain scale. The primary outcome was whether there were any differences in the decrease rate in pain scale between the two groups.Result: The average age of the 55 patients was 49.9 ± 13.5 years, and prior to the clinical visit, the patients ex-perienced an average of 2.4 ± 2.2 days of dysuria symptoms. The average numerical pain scale score for dysuria was 4.98 ± 2.18. Thirty-four patients (61.8%) showed positive culture results, and E. coli was the most commonly found bacteria, cultured in 32 patients.Fifty-one patients visited the clinic on day 7, and 42 (76.4%) reported symptom improvement, while nine patients (16.3%) had persistent symptoms. The follow-up numerical pain score was 0.39 ± 1.02 points. The pain score was dramatically decreased after medication. No difference was observed in the magnitude of the pain scale reduction between the two groups (P = 0.134). However, group II showed faster symptom resolution (P = 0.035) at the third administration (day 1.5).Conclusion: Combination therapy with NSAIDs and antibiotics for AUC patients can improve symptoms faster during two restricted activity days when patients have difficulty performing daily living activities.

To identify prognostic factors that may predict the amount of long-term visual improvement after idiopathic epiretinal membrane removal.A retrospective study of 114 patients who underwent epiretinal membrane removal was performed. The central foveal thickness, inner retinal layer thickness, inner retinal irregularity index, length of the cone outer segment tip line defect, and length of the ellipsoid zone defect were measured. The optical coherence tomography parameters that were associated with the amount of visual improvement were determined at 24 months postoperatively.Central foveal thickness and inner retinal irregularity index were not associated with best-corrected visual acuity at 24 months (P = 0.227 and P = 0.544, respectively), whereas the lengths of cone outer segment tip line defect and ellipsoid zone defect were associated with worse best-corrected visual acuity at 24 months (P = 0.015 and P0.001, respectively). Univariate regression analysis indicated that central foveal thickness and inner retinal irregularity index were associated with visual improvement (P = 0.011 and P0.001, respectively). Multivariate regression analysis indicated that inner retinal irregularity index, a marker of the inner retinal deformation, was associated with visual improvement after adjusting for age, gender, and other optical coherence tomography findings (P0.001).Patients with preoperative inner retinal deformation were found to have significantly improved long-term visual outcomes after epiretinal membrane removal.

Importance Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed. Objective To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT). Design, Setting, and Participants This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent). Interventions Participants received 2 mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a “rescue” of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks. Main Outcomes and Measures Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95% CI of the difference entirely above −5 letters). Results Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95% CI, −2.9 to 1.6;P = .55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (−137.7 [IAI monotherapy] vs −143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]). Conclusions and Relevance Improvement in visual and/or functional outcomes was achieved in more than 85% of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15% met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined. Trial Registration ClinicalTrials.gov Identifier:NCT02120950

IMPORTANCE To reveal choroidal morphological profiles under pachydrusen. BACKGROUND Drusen in pachychoroid disorders show certain differences from conventional drusen and are recently named as "pachydrusen." This study analysed the specific choroidal morphology under pachydrusen. DESIGN This study is a cross-sectional case series. PARTICIPANTS Enrolled were 136 eyes with pachydrusen from 134 patients. METHODS The presence of pachydrusen in fundus area covered by a 12 × 9 mm2 optical coherence tomography (OCT) image was accessed in eyes with pachychoroid-related diseases or their fellow eyes using colour fundus photography and swept source OCT. Choroidal morphology under the pachydrusen was analysed using OCT B-scans and en face images. MAIN OUTCOME MEASURES Choroidal thicknesses and topographical correlation between pachydrusen and pachyvessels. RESULTS A total of 225 pachydrusen in 136 eyes were analysed. The mean number of pachydrusen was 1.65 ± 1.07 per eye. Most pachydrusen were located para- or perifoveally (37 subfoveal, 86 parafoveal and 102 perifoveal). The proportion of Haller's layer to total choroidal thickness was higher at the area of the pachydrusen compared to the subfovea (0.881 ± 0.081 vs 0.765 ± 0.111, P

Purpose This study analyzes a subset of patients with peripapillary polypoidal choroidal vasculopathy (PCV) to determine whether quantifiable pachychoroid features colocalize with disease foci. Methods Patients with PCV diagnosed by indocyanine green angiography were identified for the analysis of medical records and multimodal imaging and classified as having peripapillary or macular PCV. The ratio of Haller layer thickness to total choroidal thickness was calculated at the fovea and at the site of dilated Haller vessels that showed spatial correlation with the origin of neovascularization. Choroidal thickness was measured horizontally across the fovea and circumferentially around the temporal side of the disk to study its relationship to neovascularization. Results Three hundred and fourteen eyes of 299 patients with PCV were identified, of which 17 eyes (5%) had peripapillary disease. Although eyes with peripapillary PCV exhibited thinner subfoveal choroids than those with macular PCV, at the extrafoveal disease foci, choroidal thickness, Haller's layer thickness, and its ratio to total choroidal thickness were relatively high. Conclusion Quantitative indices of choroidal structure previously identified in macular PCV performed consistently when applied to a peripapillary PCV cohort, thus supporting the hypothesis that inner choroidal thinning and Haller vessel enlargement are mechanistically relevant to these related entities.

BACKGROUND AND OBJECTIVES The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age-dependent prognostic value of body mass index (BMI) in a large multicenter cohort of patients with non-metastatic clear cell renal cell carcinoma (nm-cRCC). METHODS This study evaluated 2092 patients with nm-cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014. RESULTS There was no significant difference in BMI between the young (

Pachychoroid is a relatively novel concept describing a phenotype characterized by attenuation of the choriocapillaris overlying dilated choroidal veins, and associated with progressive retinal pigment epithelium dysfunction and neovascularization. The emphasis in defining pachychoroid-related disorders has shifted away from simply an abnormally thick choroid (pachychoroid) toward a detailed morphological definition of a pathologic state (pachychoroid disease) with functional implications, which will be discussed in this review. Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome. These conditions all exhibit the characteristic choroidal alterations and are believed to represent different manifestations of a common pathogenic process. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders within the context of the recent findings related to pachychoroid disease.摘要: 肥厚型脉络膜疾病是近年来提出的新概念, 其描述了一类特征为脉络膜毛细血管层的静脉扩张, 并且与进行性视网膜色素上皮功能障碍和新生血管的形成有关的一类疾病。定义肥厚型脉络膜相关疾病的重点已经从简单的脉络膜厚度异常 (脉络膜肥厚) 转向影响功能的病理状态 (“肥厚型脉络膜疾病”) 的详细形态学定义, 这将在本综述中详细讨论。属于肥厚型脉络膜疾病谱的疾病, 包括中心性浆液性脉络膜视网膜病变, 肥厚型脉络膜色素上皮病变, 肥厚型脉络膜新生血管病变, 息肉状脉络膜血管病变/1型动脉瘤新生血管, 局灶性脉络膜凹陷, 视盘周围毛细脉络膜肥厚综合症。这些病症都表现出特征性的脉络膜改变, 并且被认为代表了常见致病过程的不同临床表现。 本综述基于目前已发表的文献和作者自身的临床经验以及最近在肥厚型脉络疾病的相关研究结果, 重点强调了临床表现、影像学特征、治疗要点以及目前对这些疾病发病机制的探讨。.

Preoperatively predicting postoperative kidney function is an essential step to achieve improved renal function and prevent chronic kidney disease. We introduce a novel formula especially to calculate resected and ischemic volume before partial nephrectomy. We examined whether resected and ischemic volume would have value for predicting postoperative renal function.We performed a retrospective cohort study in 210 patients who underwent robotic partial nephrectomy between September 2006 and October 2013 at a tertiary cancer care center. Based on abdominopelvic computerized tomography and magnetic resonance imaging we calculated resected and ischemic volume by the novel mathematical formula using integral calculus. We comparatively analyzed resected and ischemic volume, and current nephrometry systems to determine the degree of association and predictability regarding the severity of the postoperative functional reduction.On multivariable analysis resected and ischemic volume showed a superior association with the absolute change in estimated glomerular filtration rate/percent change in estimated glomerular filtration rate (B = 6.5, p = 0.005/B = 6.35, p = 0.009). The ROC AUC revealed accurate predictability of resected and ischemic volume on the stratified event of an absolute change in estimated glomerular filtration rate/event of percent change in estimated glomerular filtration rate compared to 3 representative nephrometry systems. The calibration plot of this model was excellent (close to the 45-degree line) within the whole range of predicted probabilities.We report a method of preoperatively calculating resected and ischemic volume with a novel formula. This method has superior correlation with the absolute and percent change in estimated glomerular filtration rate compared to current nephrometry systems. The predictive model achieved a strong correlation for the absolute and percent change in estimated glomerular filtration rate.