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To identify optical coherence tomography (OCT) biomarkers, including thin and thick double-layer sign (DLS) for the progression from intermediate AMD (iAMD) to exudative macular neovascularization (MNV) over 24 months.Retrospective cohort study.Setting: Retina consultants of Texas.458 eyes of 458 subjects with iAMD in at least 1 eye with 24 months of follow-up data.The following biomarkers were assessed at baseline: high central drusen volume (≥0.03 mmDuring follow-up, 18.1% (83 of 458) of eyes with iAMD progressed to exudative MNV. Thick DLS, IHRF, and fellow eye exudative MNV were found to be independent predictors for the development of exudative MNV within 2 years. The baseline frequencies, odds ratios, 95% confidence intervals, and P values for these biomarkers were as follows: thick DLS (9.6%, 4.339, 2.178-8.644; P.001), IHRF (36.0%, 2.340, 1.396-3.922; P = 0.001), and fellow eye exudative MNV (35.8%, 1.694, 1.012-2.837; P = .045).Thick DLS, IHRF, and fellow eye exudative MNV were associated with an increased risk of progression from iAMD to exudative MNV. These biomarkers, which are readily identified by the review of OCT volume scans, may aid in risk prognostication for patients and for identifying patients for early intervention trials.

To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population.Genome-wide association study (GWAS).Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses.We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants.Associations of genetic variants with AMD.A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P5.0 × 10Our findings imply shared genetic components conferring the risk of both AMD and CSC.Proprietary or commercial disclosure may be found after the references.

This study investigated one-year outcomes of treatment with one session of intravitreal recombinant tissue plasminogen activator, ranibizumab, and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). An extended study of a previous prospective trial of this treatment modality in PCV patients was conducted in 64 patients (64 eyes). Early Treatment Diabetic Retinopathy Study (ETDRS) score, central retinal thickness (CRT), and central pigment epithelial detachment thickness (CPEDT) before and 1, 3, and 12 months after treatment were analyzed. Mean ETDRS score increased from 58 at baseline to 64 letters (p = 0.0122), CRT decreased from 543 to 192 μm (p < 0.0001), and CPEDT decreased from 161 to 103 μm (p = 0.0668) at 3 months and were maintained until 12 months. Complications requiring reoperation occurred within one month in four eyes. Recurrence was observed in 46 eyes (72%), and 1.6 ± 1.5 (0–7) intravitreal aflibercept injections were given pro re nata. Univariate and multivariate analyses identified CPEDT as the pre- and post-treatment factor affecting 12-month ETDRS score (p < 0.0001). Improved visual acuity stabilized 3 months after treatment. Although 72% of patients experienced recurrence, an average of 1.6 aflibercept injections/patient maintained visual acuity up to 12 months. CPEDT was the most important factor associated with visual outcome.

Background Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment. Case presentation A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography. Conclusions Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.

Surgical treatment of myopic foveoschisis (MF) can result in a macular hole in 11–17% of patients that may lead to poor visual outcomes and progression to macular hole retinal detachment. We evaluated the benefit of vitrectomy to treat MF using the inverted internal limiting membrane (ILM) flap and fovea-sparing ILM techniques. We studied 20 eyes of 20 patients (7 men, 13 women) with high MF (mean axial length, 29.3 ± 1.7 mm). MF was classified by optical coherence tomography findings: retinoschisis (7 eyes) or foveal detachment (13 eyes). Between October 2013 and June 2021, we performed vitreous surgery in all 20 patients, employing both techniques. Air tamponade was used in 4 eyes, SF6 gas in 10 eyes, and C3F8 gas in 6 eyes. All patients stayed in the face-down position for one full day postoperatively. Visual acuity and foveal contour were analyzed using optical coherence tomography before surgery and at 3 and 6 months postoperatively. LogMAR visual acuity was 0.46 before surgery, with a significant improvement at 3 months (0.34) and at 6 months (0.2) postoperatively (p = 0.024, p < 0.001, respectively). In all patients, the foveal contour showed improvement without macular hole formation after surgery. These results show that vitrectomy, performed using the inverted ILM flap and fovea-sparing ILM technique, is effective for treating MF.

Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD.This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography.The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 μm at baseline to 216.9 ± 110.2 μm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group.Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

Pachychoroid neovasculopathy (PNV) is treated with antivascular endothelial growth factor (VEGF) injection and photodynamic therapy (PDT), but no curative treatment has yet been established. We aimed to clarify the treatment results of a reduced dose of PDT for PNV. The subjects were 27 eyes of 27 patients (male:female = 20:7, mean age 58.9 years). PDT, at 2/3 of the conventional dose (2/3PDT), was administered once. The patients were then observed for one year. Eyes with polypoidal choroidal vasculopathy (PCV) were excluded. We investigated the associations among the central retinal thickness, choroidal thickness, and visual acuity changes before treatment and one, three, six and 12 months after PDT. When serous retinal detachment was increased or unchanged or new hemorrhages were observed, as compared with pretreatment findings, intravitreal injection of an anti-VEGF agent was performed. Visual acuity was significantly improved, as compared to before treatment, at three, six, and 12 months after 2/3PDT. Foveal retinal thickness was significantly decreased after versus before treatment in the 2/3PDT group (p &lt, 0.001). Foveal choroidal thickness was also significantly reduced in the 2/3PDT group (p = 0.001). Additional intravitreal anti-VEGF agent injections were administered to three patients (11%), while 24 (89%) required no additional treatment during the one-year follow-up period. For PNV without polyps, 2/3PDT appears to be effective.

Central serous chorioretinopathy (CSC) is a disease of unknown etiology, but half-dose photodynamic therapy (hPDT) is well known to be effective for CSC. Infrared reflectance (IR) has been shown to be effective for detecting retinal pigmented epithelial and choroidal lesions, but no reports have focused on chorioretinal changes using IR images after as compared to before hPDT. This study aimed to clarify the features of IR images as well as retinal and choroidal morphological changes before and after treatment with verteporfin hPDT for CSC. We also examined prognostic factors associated with CSC treatment. This was a retrospective study that included 140 eyes of 140 patients (male/female ratio 122:18, mean age 53.4 &plusmn, 10.8 years) diagnosed with CSC who underwent hPDT in our hospital during the period from April 2015 to December 2018. We determined changes in visual acuity, therapeutic efficacy, central retinal thickness (CRT), central choroidal thickness (CCT), and IR images at one and three months after hPDT as compared to before treatment. Dry macula was defined as a complete resolution of serous retinal detachment after hPDT. History of smoking, disease duration, presence of drusen, presence of retinal pigment epithelium abnormalities, type of fluorescein angiographic leakage, and presence of choroidal vascular hyperpermeability were investigated as prognostic factors associated with treatment efficacy. CRT and CCT were measured using optical coherence tomography (Spectralis HRA-2, Heidelberg Engineering), and IR images after versus before treatment were compared using ImageJ software (version 1.52) to calculate the mean luminance for a 3 &times, 3 mm area in the macula. Compared with the values before treatment, CCT, CRT, and visual acuity showed significant improvements at one and three months after treatment, and the mean luminance of IR images was also significantly increased. Furthermore, the luminance on IR images tended to rise, though the values at one month and three months after treatment did not differ significantly. Disease duration was significantly associated with dry macula one month after treatment, and visual acuity and CRT before hPDT were both significantly related to dry macula three months after treatment. IR images tended to improve over time, from before treatment through one and three months after hPDT.

The purpose of this study was to quantitatively analyze heart rate variability (HRV) in patients with central serous chorioretinopathy (CSC) by using a smartphone-based application (ANBAI: DUMSCO Inc.) for measurement, and to clarify its relationships with CSC. The subjects were 64 CSC patients (mean age 48.7 ± 7.6 years, 57 males and 7 females). After providing consent, the patients downloaded ANBAI apps to their smartphones. HRV was measured by photoelectric volume pulse wave measurement with a smartphone camera each morning for a minimum of 1 week. The primary outcome was to analyze HRV by calculating log LF/HF (Low Frequency/High Frequency components), an index of autonomic tone, which was then compared with a control group of 35,226 individuals from the application. Secondary outcome measures included disease duration, body mass index, exercise habits, smoking history, steroid use, occupation, lifestyle regularity, psychological fatigue, physical fatigue, and average sleep time. The log LF/HF was significantly higher in the patient group than in the control group (P P = 0.019). Analysis of HRV in CSC patients showed an impairment of the autonomic nervous system. Exercise habits may also be associated with CSC.

Objective This study aimed to evaluate the usefulness of a new wet laboratory (wet lab) system using porcine eyes with eyelids. Design Teaching device trial. Participants Porcine eyes with orbital tissues and eyelids. Methods Twenty porcine eyes with orbital tissues and eyelids were enucleated from pigs butchered at age 6 months. These eyes were positioned in the eye sockets of a model head and stabilized with a pin. Eye draping, dressing with tape, and speculum placement were conducted. The vertical and horizontal widths of the palpebra under the speculum setting were compared with those of 55 patients who underwent cataract surgery. The rotation and torsion of the porcine eye in the new wet lab system were also compared with those of a conventional wet lab system. For comparison with actual cataract surgery, 5 ophthalmologists, including residents, were asked to respond to a questionnaire survey. Results The horizontal widths of the palpebra under the speculum setting were 27.5 ± 3.1 mm in porcine eyes and 28.6 ± 5.1 mm in human eyes, and the vertical widths were 16.9 ± 1.3 mm and 16.1 ± 1.5 mm (p = 0.53, 0.05). The amounts of rotation and torsion were significantly greater with the new wet lab system. Ophthalmologists evaluated the new wet lab system as being more realistic than the conventional system, in terms of both natural eye movement and restriction of the surgical field by the eyelid and the speculum. Conclusions Wet lab training using porcine eyes with eyelids is more practical than older systems as it reproduces an ocular surgical field very similar to that of humans.

Purpose To compare the findings of optical coherence tomography angiography (OCTA) with indocyanine green angiography (ICGA) in polypoidal choroidal vasculopathy (PCV) that was divided into two types: polypoidal choroidal neovascularisation (CNV) and typical PCV (type 2 PCV). Methods We studied a retrospective case series of 32 patients with treatment-naive PCV (24 men, eight women; mean age 65.4 years). PCV was categorised into polypoidal CNV (type 1 PCV) and type 2 PCV based on ICGA findings. OCTA was performed using the RTVue XR Avanti. Macular cubes (3×3 or 6×6 mm) were acquired. To evaluate the locations of polyps and branched vessel networks (BVNs), we used B-mode scan. Results OCTA clearly depicted only 17% of the type 1 PCV polyps and 46% of the type 2 PCV polyps which were detectable by ICGA. All type 1 PCV polyps detectable by OCTA were located just beneath the retinal pigment epithelium (RPE). On the other hand, type 2 PCV polyps were detected in various locations. All BVNs of type 1 PCV were located between the RPE and Bruch9s membrane on OCTA images. However, the BVNs in type 2 PCV were located mainly under the RPE, though some were located in the choroid. Conclusions Polyps of type 1 PCV were more difficult to detect with OCTA than those of type 2 PCV. Polyps of type 1 PCV were located just beneath the RPE. The BVNs of type 1 PCV were located between the RPE and Bruch9s membrane.

Background To evaluate the efficacy of epiretinal membrane removal in patients with good best-corrected visual acuity (BCVA) for improving visual function and quality of life (QOL). Methods This prospective case study compared 37 subjects with preoperative BCVA ≦ 0.046 logMAR (Good group) to 35 patients with 0.10–0.52 logMAR (Moderate group) at 3 and 6 months. Linear mixed-effect models were used for statistical analysis. The primary outcome was the horizontal metamorphopsia score (MH) at 6 months postoperatively (post-6 M), while secondary outcomes were postoperative BCVA, vertical metamorphopsia score (MV), aniseikonia, stereopsis and central foveal thickness. In the Good group, QOL was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) at 6 and 12 months. Results MH was significantly improved at post-3 M and post-6 M in the both groups but there were no significant differences between the two groups. MV showed no improvement at the final observation in either group. LogMAR BCVA was significantly improved at post-6 M in the Good group, which had significantly better vision than the Moderate group. Preoperative vertical and horizontal aniseikonia scores remained unchanged in the Good group at post-6 M but worsened in the Moderate group. The NEI VFQ-25 score improved in the Good group, reflecting improved general health, general vision, and mental health. Conclusions Early epiretinal surgery for patients with BCVA ≦ 0.046 logMAR was effective for improvement of HM, BCVA, and QOL and prevented worsening of aniseikonia. Trial registration UMIN000021220. Registered 10 September 2015. UMIN Clinical Trials Registry.

A patient with acquired optic disc pit (ODP) maculopathy underwent vitrectomy with anterior capsule transplantation to the ODP and gas tamponade. Structural changes were evaluated by enhanced depth imaging optical coherence (OCT) tomography. During vitrectomy, the eye was confirmed to have preexisting posterior vitreous detachment. Postoperative OCT showed complete closure of the optic pit resulting in rapid absorption of subretinal fluid. The authors' observations suggest that the anterior capsule is a useful material for achieving optic pit closure. To the authors' knowledge, this is the first report describing application of the anterior capsule to the treatment of ODP maculopathy. [ Ophthalmic Surg Lasers Imaging Retina. 2019;50:649–652.]

Purpose To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects. Materials and methods The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7±3.9 years, range 23–40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress. Results Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38±0.49 before intake, 4.28±0.85 after intake; p p =0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake ( p Y =1.01 X 1 −0.005 X 2 −0.003 X 3 −0.017 X 4 ( Y =change in CFVR after 2 weeks of chocolate intake, X 1 =intake of dark (but not white) chocolate, X 2 =MDA-LDL, X 3 =TG, X 4 =HR). Conclusion Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.

It has been reported that mental stress is an independent risk factor for cardiovascular events and impairs coronary circulation. Lavender aromatherapy, one of the most popular complementary treatments, is recognized as a beneficial mental relaxation therapy. However, no study has examined the effect of this therapy on coronary circulation. We aimed to assess the effect of lavender aromatherapy on coronary circulation by measuring coronary flow velocity reserve (CFVR) with noninvasive transthoracic Doppler echocardiography (TTDE).We enrolled 30 young healthy men (mean age 34+/-4.7 years, range 24-40 years). Coronary flow velocities in the left anterior descending coronary artery were recorded by TTDE at rest and during hyperemia induced with an intravenous infusion of adenosine triphosphate (ATP). CFVR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. CFVR was assessed at baseline and immediately after lavender aromatherapy (four drops of essential oil diluted with 20 ml of hot water and inhaled for 30 min). Simultaneously, serum cortisol was measured as a marker of stress hormones. To exclude the relaxation effects of rest, the same measurements were repeated in the same volunteers without aromatherapy as a control study.CFVR measurements were obtained in all volunteers (100%). Blood pressure and heart rate responses to ATP infusion were not affected by lavender aromatherapy. Serum cortisol significantly decreased after lavender aromatherapy (8.4+/-3.6 to 6.3+/-3.3, p0.05), but remained unchanged in controls (9.1+/-3.5 to 8.1+/-3.9, p=ns). In addition, CFVR significantly increased after lavender aromatherapy (3.8+/-0.87 to 4.7+/-0.90, p0.001), but not in controls (3.9+/-0.8 to 3.9+/-0.8, p=ns).Lavender aromatherapy reduced serum cortisol and improved CFVR in healthy men. These findings suggest that lavender aromatherapy has relaxation effects and may have beneficial acute effects on coronary circulation.

Purpose To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattler's (CS) layer and/or the large vessel layer in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm. Methods We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan. Results Total choroidal thicknesses at each of the five sites were related to subject age (P

To evaluate left atrial (LA) function in subjects with early stage primary hypertension (HT) and without enlargement of LA, we used transthoracic echocardiogram and measured LA volumetric emptying fraction and compared the results with those in healthy volunteers.42 subjects with early stage primary HT (21 males, aged 61+/-12 years), within 1 year of HT diagnosis and starting initial treatment, were enrolled in the study. An additional inclusion criterion was normal sinus rhythm electrocardiogram without enlargement of LA. As the control group, 31 healthy volunteers with normal sinus rhythm electrocardiogram (13 male, aged 57+/-11 years) were enrolled. Maximum and minimum volume of LA (LAV max and min, respectively) were selected manually and visually in B mode images acquired from a four-chamber view from apex of left ventricle (LV) using a modified Simpson method, and the LA emptying fraction (LAEF) was calculated by the following formula: LAV min/LAV max x 100 (%).There were no significant differences in age, male:female ratio, end-diastolic and end-systolic LV diameter, LA maximum volume, LV ejection fraction and E/A in mitral annulus between the two groups. However, we found that end-diastolic inter-ventricular septum thickness and end-diastolic LV posterior wall thickness were significantly larger in the HT group in comparison with the control group (P0.01), but the HT group did not fit the classical criteria of LV myocardial hypertrophy. The systolic and diastolic blood pressure, the end-diastolic and end-systolic volume of LV, the total weight of LV myocardium and the LAEF were significantly higher in the HT group than in the control group (P0.05).In subjects with early stage primary HT with normal sinus rhythm, in spite of a normal LAV, the LAEF may increase. This increase of LAEF may be regarded as one of the compensatory reactions against preload to the left side of the heart and precedes the occurrence of LA enlargement.