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PURPOSE: Trend analysis of visual field (VF) global indices may underestimate the rate of progression in severe glaucoma due to the influence of test points without detectable sensitivity. To test this hypothesis, we compared the rates of change of VF global indices with and without exclusion of undetectable points at various disease stages. METHODS: Six hundred and forty-eight eyes of 366 glaucoma patients with 8 or more reliable 30–2 standard automated perimetry over more than 2 years were enrolled. We calculated targeted mean total deviation (TMTD) by averaging total deviation except points which were consistently undetectable in 3 baseline tests. Eyes were classified as early (≥ −6 dB), moderate (− 6 dB to −12 dB), advanced (−12 dB to −20 dB), and severe (< −20 dB) based on baseline mean deviation (MD). The rates of change of MD and TMTD in each stage were statistically compared RESULTS: Mean age ± standard deviation at baseline was 56.9 ± 11.9 years. The MD slope (−0.34 dB/year) in severe glaucoma was significantly slower than TMTD slope (−0.42 dB/year, P=0.028) and was slower than MD slopes in the other stages. Difference between MD slopes and TMTD slopes was most prominent in eyes with MD values less than −25 dB (P=0.002). CONCLUSIONS: Undetectable locations in eyes with severe glaucoma may lead to an underestimate of the rates of VF progression. Trend analysis of TMTD rather than global indices offers a practical and simple approach for alleviating underestimation of VF progression in severe glaucoma.

Childhood glaucoma is one of the major causes of blindness in children, however, its diagnosis is of great challenge. The study aimed to demonstrate and evaluate the performance of a deep-learning (DL) model for detecting childhood glaucoma based on periocular photographs. Primary gaze photographs of children diagnosed with glaucoma with appearance features (corneal opacity, corneal enlargement, and/or globe enlargement) were retrospectively collected from the database of a single referral center. DL framework with the RepVGG architecture was used to automatically recognize childhood glaucoma from photographs. The average receiver operating characteristic curve (AUC) of 5-fold cross-validation was 0.91. When the 5-fold result was assembled, the DL model achieved an AUC of 0.95 with a sensitivity of 0.85 and specificity of 0.94. The DL model showed comparable accuracy to the pediatric ophthalmologists and glaucoma specialists in diagnosing childhood glaucoma (0.90 vs 0.81, p = 0.22, chi-square test), outperforming the average of human examiners in the detection rate of childhood glaucoma in cases without corneal opacity (72% vs. 34%, p = 0.038, chi-square test), with a bilateral corneal enlargement (100% vs. 67%, p = 0.03), and without skin lesions (87% vs. 64%, p = 0.02). Hence, this DL model is a promising tool for diagnosing missed childhood glaucoma cases.

Non-alcoholic steatohepatitis (NASH) is a progressive subtype of non-alcoholic fatty liver disease (NAFLD) that is closely related to cardiovascular disease (CVD). Nitric oxide (NO) plays a critical role in the control of various biological processes. Dysfunction of the NO signaling pathway is associated with various diseases such as atherosclerosis, vascular inflammatory disease, and diabetes. Recently, it has been reported that NO is related to lipid and cholesterol metabolism. Chronic NO synthase (NOS) inhibition accelerates NAFLD by increasing hepatic lipid deposition. However, the detailed relationship between NO and abnormal lipid and cholesterol metabolism in NAFLD/NASH has not been completely explained. We aimed to determine the effects of NOS inhibition by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME), a NOS inhibitor, on NASH and CVD via lipid and cholesterol metabolism.Stroke-prone spontaneously hypertensive rats were fed a high-fat and high-cholesterol diet for 8 weeks and administered L-NAME for the last 2 weeks. Following blood and tissue sampling, biochemical analysis, histopathological staining, quantitative RT-PCR analysis, and western blotting were performed.L-NAME markedly increased hepatic triglyceride (TG) and cholesterol levels by promoting TG synthesis and cholesterol absorption from the diet. L-NAME increased the mRNA levels of inflammatory markers and fibrotic areas in the liver. Cholesterol secretion from the liver was promoted in rats administered L-NAME, which increased serum cholesterol. L-NAME significantly increased the level of oxidative stress marker and lipid deposition in the arteries.NOS inhibition simultaneously aggravates NASH and atherosclerosis via hepatic lipid and cholesterol metabolism.

Background The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. Methods Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. Results SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (Pmeta = .0019, OR = 4.55, I2 = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (Pmeta = .81, OR = 1.05; I2 = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. Conclusions In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.

To compare early-stage intrableb structural changes after Ex-PRESS surgery using anterior-segment optical coherence tomography between primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG).Twenty-five POAG eyes and 15 XFG eyes that underwent Ex-PRESS surgery were evaluated. Intrableb images were classified into four categories based on previously reported scattering intensity: high-, medium-, and low-scattering walls and fluid-filled spaces. Bleb measurements were evaluated in both groups throughout 6 postoperative months. The 3-year surgical success was defined by the criteria intraocular pressure (IOP)18 mmHg and IOP15 mmHg with or without medications.The fluid-filled space volume at 3 and 6 months (P = 0.005 and P = 0.022, respectively) and the volume ratio of the low-scattering wall to the bleb wall (P = 0.028) at 6 months were significantly smaller in XFG than POAG postoperatively. The volume ratio of the high-scattering wall to the bleb wall was correlated positively (P = 0.007) with the IOP, and that of the low-scattering wall to the bleb wall was correlated negatively (P = 0.002) with the IOP in XFG. The 3-year surgical success rates for both criteria were significantly lower in XFG than POAG.Fluid-filled spaces were smaller in XFG than in POAG after Ex-PRESS surgery. The proportion of the high-scattering wall tended to increase and the low-scattering wall tended to decrease in XFG eyes with high IOP. Early-stage intrableb structural changes differed between POAG and XFG and may affect the prognosis.Our cutting-edge observation of intrableb fibrosis can be an important predictor of the surgical outcome.

The aim of this study was to report a technique for the removal of dislocated polymethyl methacrylate (PMMA) intraocular lenses (IOLs) in glaucomatous eyes.Dislocated PMMA IOLs were removed from the inferior sclerocorneal incision, and sutureless intrascleral fixation of each IOL was performed to preserve the intact superior conjunctiva and sclera for future trabeculectomy or to maintain a functional filtering bleb of trabeculectomy.In two cases, the condition of the bleb did not change, while the intraocular pressure improved or did not change after the procedures. IOL fixation was stable with no complications, such as tilt, decentration, or extrication of the IOL haptics.This procedure of preserving the superior conjunctiva and sclera can maintain the function of the bleb, superior cornea and sclera and may contribute to the success of future trabeculectomy.

Background Indapamide, a sulfonamide diuretic used to treat hypertension, has been reported to have ocular side effects of acute angle-closure glaucoma, transient myopia and choroidal effusion whose immediate etiology is uncertain. This report aims to clarify the nature of indapamide-induced edema of the entire eyeball using multimodal imaging. Case presentation A 60-year-old woman who was following a long-term carbohydrate-restricted diet and receiving oral treatment for hypertension was referred to our department for eye pain. Indapamide (1 mg daily) was prescribed for uncontrolled hypertension 5 days before her visit; she took the medication for only 3 days and then stopped due to dry eye. However, she began to feel eye pain the day after her last dose, and the pain gradually intensified. She experienced no decrease in visual acuity at the initial visit; however, an extremely shallow anterior chamber was observed in both eyes, along with a slight increase in intraocular pressure. For differential diagnosis, ocular manifestations were evaluated with wide-field fundus photography, optical coherence tomography (OCT) of both anterior and posterior segments, fluorescein / indocyanine green angiography, ultrasound biomicroscopy and head magnetic resonance, showing edema of the entire eyeball. Treatment with tropicamide and phenylephrine hydrochloride drops resulted in rapid recovery of the anterior chamber depth and disappearance of the choroidal effusion within 3 days. Conclusions Multimodal imaging is useful for diagnosing drug-induced choroidal effusion by evaluating ocular conditions before and after treatment.

A high-fat/high-cholesterol (HFC) diet, but not a high-cholesterol (HC) diet, is known to induce elevated serum apolipoprotein E (apoE)-rich high-density lipoprotein (HDL) levels in animal models. However, the exact mechanisms by which the combination of dietary fat and cholesterol induces apoE-rich HDL production is not well understood. Here, we investigated the effects of dietary fat and cholesterol on serum lipoprotein profiles and hepatic mRNA expression that are associated with HDL production, cholesterol transport, and bile acid metabolism. Male Sprague-Dawley rats were fed HFC, HC, high-fat, or control diets and then evaluated. The HFC diet induced significant increases in hepatic free-cholesterol accumulation (1.4-fold, p 0.01) and serum apoE-rich HDL cholesterol (8.7-fold, p 0.001) levels compared with the HC diet. The apoE-rich HDL induced by the HFC diet was remarkably rich in free cholesterol. Liver gene-expression was mostly similar between the HC and HFC diet groups. However, there was a significant increase of ATP-binding cassette transporter A1 (ABCA1) levels in the HFC group compared to the HC group for both mRNA (1.9-fold, p 0.001) and protein (6.6-fold, p 0.01). These results suggest that an increase in apoE-rich HDL induced by dietary fat and cholesterol may be involved in cholesterol efflux from the liver through increased ABCA1-mediated free-cholesterol efflux.

We evaluated regression of iris neovascularization (INV) using en-face anterior-segment optical coherence tomography angiography (AS-OCTA) after anti-vascular endothelial growth factor (VEGF) therapy. Seven consecutive eyes with INV were examined before and after anti-VEGF therapy, and all AS-OCTA scans were obtained using a swept-source OCTA system with an anterior-segment lens adapter. Slit-lamp microscopy photography and anterior indocyanine green angiography also were performed. Quantitative analyses of the vascular density, vascular lacunarity, and fractal dimension on AS-OCTA images were performed. AS-OCTA visualized the INV as signals around the pupillary margin, which corresponded to the vasculature confirmed by slit-lamp microscopy. After anti-VEGF drug injection, regression of INV was observed by AS-OCTA in all eyes (100%). The vascular density decreased and vascular lacunarity increased significantly after anti-VEGF therapy. This pilot study demonstrated the ability of AS-OCTA not only to detect but also to evaluate INV. Further study is warranted to improve the algorithm for delineating the iris vasculature to decrease artifacts.

We report the rare case of an adenoma of the nonpigmented ciliary epithelium (NPCE). A 67-year-old healthy man presented with a regularly shaped and nonpigmented mass at the iris root of his right eye. His best-corrected visual acuity was 1.5 with normal intraocular pressure. During observation, the size of the tumor remained stable for 1.5 years but then rapidly grew, extending through the iris, and gradually enlarged to the point of compressing the iris. Ultimately, an iridocyclectomy with scleral resection under a lamellar scleral flap was performed. The histopathologic features of the resected tissue were consistent with adenoma of the NPCE. Histopathological analysis showed that the tumor consisted of both tubular and solid components. There were solid lesions inside of the ciliary epithelium and tubular lesions outside. We observed positive immunoreactivity to vimentin and cytokeratin CK (AE1/AE3) and negative reactivity to S-100 and CD68, both rarely associated with adenoma of NPCE. During 1 year of follow-up after the iridocyclectomy, no signs of tumor recurrence were observed.

Purpose Recent studies have suggested that OCT-based classification of parapapillary atrophy (PPA) may be helpful in distinguishing glaucomatous from myopic optic disc changes. However, the pathologic implications of PPA may be different in highly myopic eyes that exhibit optic disc deformations distinct from low-to-moderate myopia. Therefore, we conducted the current study to investigate factors associated with OCT-defined PPA zones measured in en face reconstructed swept-source OCT (SS OCT) images in highly myopic eyes. Design Retrospective, cross-sectional study. Participants Seventy-seven eyes of 55 subjects with high myopia (spherical equivalent refractive error ≤ −8 diopters or axial length ≥26.5 mm) were included. Forty-nine eyes of 33 subjects had open-angle glaucoma (MG group), and 28 eyes of 22 did not (M group). Methods The beta zone and the gamma zone PPA areas were measured in en face images reconstructed from 3-dimensional SS OCT volumetric scans. Relationships between the PPA areas and patient characteristics such as glaucoma, axial length, and age were evaluated using multivariate mixed-effects models. The diagnostic capability of each PPA zone area for detecting glaucoma was assessed with the receiver operating characteristic (ROC) curve analysis. Main outcome measures were areas of the beta zone and the gamma zone PPA measured in en face OCT images and factors associated with each PPA area. Results Average ± standard deviation area of the beta and the gamma zone was 1.1±1.1 and 1.1±1.1 mm2. The gamma zone was positively correlated with axial length (P = 0.006) and age (P = 0.04951) but not with glaucoma (P = 0.776). The beta zone was positively correlated with both axial length (P = 0.039) and glaucoma (P = 0.011). The areas under the ROC curve of the beta zone and the gamma zone areas were 0.686 and 0.560, respectively. Conclusions The OCT-defined beta zone was associated with glaucoma and axial length, whereas the gamma zone was correlated with axial length but not with glaucoma, in highly myopic eyes. The OCT-based classification showed poor diagnostic performance for glaucoma. Relationships between PPA areas and baseline clinical factors may be different between high myopia and non–high myopia.

Purpose This study aimed to quantitatively analyze the association between follow-up duration and the severity of limbal stem cell deficiency (LSCD) or visual acuity in patients with aniridia. Methods A total of 52 eyes of 27 patients with aniridia were enrolled at Osaka University Hospital. Medical records were retrospectively reviewed to obtain information on the severity of LSCD and corrected distance visual acuity (CDVA). LSCD severity was based on a modified severity grading scale. We used an ordered logistic regression model to examine the association between follow-up duration and LSCD severity, and a linear regression model with a generalized linear mixed model for the association between follow-up duration and visual acuity. Results The mean follow-up duration was 5.2 ± 6.3 years. The mean age at the last follow-up visit was 40.5 ± 18.9 years. The mean CDVA was 1.52 ± 1.09 logMAR. At the last follow-up, 1 examined eye (1.9%) was categorized as stage 0, 7 (13.5%) as Ia, 9 (17.3%) as Ib, 5 (9.6%) as Ic, 2 (3.8%) as IIb, 12 (23.1%) as IIc, and 11 (21.2%) as III. Five eyes (9.6%) were unclassifiable. There was a significant association between follow-up duration and LSCD severity (odds ratio per +1 year, 1.41; P < 0.001). CDVA significantly decreased as follow-up duration increased. Each increase of 1 year in the follow-up duration was associated with a mean difference of +0.021 logMAR (95% confidence interval [CI] 0.01–0.03; P < 0.001). Conclusions We quantitatively demonstrate that LSCD severity and visual impairment significantly progress as follow-up duration increases.

Background High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents a small portion of plasma HDL. We recently established a method for measuring plasma apoE-rich HDL. This study aimed to investigate the relationship between metabolic syndrome (MetS) and apoE-rich HDL levels. Methods The apoE-rich HDL-cholesterol (HDL-C) levels and metabolic characteristics of 113 patients were analyzed. Results The MetS group (n = 58) had significantly lower apoE-rich HDL-C and a lower apoE-rich HDL-C/HDL-C ratio (apoE-HDL (%)) compared to the non-MetS group. The prevalence of MetS was increased when apoE-HDL (%) decreased. In simple regression analyses, apoE-HDL (%) was significantly inversely correlated with visceral fat area (rs = −0.370, P Conclusions Plasma apoE-rich HDL levels might be a valuable indicator of MetS. These findings may help further understand HDL subfraction analysis in cardiometabolic diseases.

To evaluate the capability of anterior segment Scheimpflug imaging for detecting primary angle closure disease (PACD): primary angle closure suspect, primary angle closure, and primary angle closure glaucoma, using cutoff points derived from reference databases of healthy subjects. Eighty-seven patients with PACD and 49 age-matched control subjects were included. We evaluated the sensitivity and specificity of anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) to differentiate patients with PACD from controls. Additionally, the study’s raw data was analyzed via receiver operating characteristic curves for comparison. One standard deviation from the normative data’s mean values was used as the cutoff point and yielded a sensitivity and specificity of 96.2% and 92.6% for ACD, 97.1% and 75.9% for ACV, and 93.3% and 72.2% for ACA, respectively. Receiver operating characteristic analysis of the raw data showed the area under the curve to be 0.984, 0.975, and 0.931 for ACD, ACV, and ACA, respectively. Our study demonstrated that the parameters of anterior segment Scheimpflug imaging, particularly ACD, accurately discriminate PACD. This was the first study to validate the device’s normative data in a separate population. With its high reproducibility, ease of use, non-invasiveness, and speed, anterior segment Scheimpflug imaging is a potentially powerful screening tool for PACD.

To evaluate the relationship between peripapillary tilt and visual field (VF) defects in glaucomatous eyes with axial myopia. Retrospective cross-sectional study. One hundred four eyes of 104 patients with primary open-angle glaucoma (POAG) with myopia were included (52 eyes with high myopia [HM], 26.5 mm ≤ axial length [AL]

Aim: Non-alcoholic steatohepatitis (NASH) increases cardiovascular risk regardless of risk factors in metabolic syndrome. However, the intermediary factors between NASH and vascular disease are still unknown because a suitable animal model has never been established. The stroke-prone (SP) spontaneously hypertensive rat, SHRSP5/Dmcr, simultaneously develops hypertension, acute arterial lipid deposits in mesenteric arteries, and NASH when feed with a high-fat and high-cholesterol (HFC) diet. We investigated whether SHRSP5/Dmcr affected with NASH aggravates the cardiac or vascular dysfunction. Method: Wister Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 rats each, and fed with a SP or HFC diet. After 8 weeks of HFC or SP diet feeding, glucose and insulin resistance, echocardiography, blood biochemistry, histopathological staining, and endothelial function in aorta were evaluated. Results: We demonstrate that SHRSP5/Dmcr rats fed with a HFC diet presented with cardiac and vascular dysfunction caused by cardiac fibrosis, endothelial dysfunction, and left ventricular diastolic dysfunction, in association with NASH and hypertension. These cardiac and vascular dysfunctions were aggravated and not associated with the presence of hypertension, glucose metabolism disorder, and/or obesity. Conclusions: SHRSP5/Dmcr rats may be a suitable animal model for elucidating the organ interaction between NASH and cardiac or vascular dysfunction.

Lavender essential oil (Lvn) has anti-inflammatory effects in an ovalbumin-sensitized murine model of asthma, and inhibits inflammatory cell infiltration into the lungs. The anti-inflammatory effects of Lvn on cell adhesion molecules are not clear. Here we evaluated the effects of Lvn and its main constituents, linalyl acetate (LA) and linalool (LO), on the expression of tumor necrosis factor-alpha (TNF-α)-induced cell adhesion molecules in murine brain endothelial bEnd.3 cells and human umbilical vein endothelial cells (HUVECs). The bEnd.3 cells were treated with Lvn, LA, or LO and subsequently stimulated with TNF-α. The mRNA expression levels of cell adhesion molecules were detected using RT-PCR. E-selectin and P-selectin protein and phosphorylated-NF-κB p65 were detected by western blotting. The effects of Lvn on HUVECs were measured by RT-PCR. In bEnd.3 cells, Lvn and LA suppressed TNF-α-induced E-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and phosphorylated-NF-κB p65 in the nucleus; LO did not suppress P-selectin or phosphorylated-NF-κB p65. Lvn inhibited TNF-α-induced E-selectin mRNA in HUVECs. These results indicate that Lvn and LA inhibit TNF-α-induced cell adhesion molecules in endothelial cells through the suppression of NF-κB activation. Consequently, Lvn or other essential oils including LA may be useful as alternative anti-inflammatory medicines.

PURPOSE To determine the prevalence of errors in segmentation of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) boundary in spectral-domain optical coherence tomography (SDOCT) images, and to identify factors associated with the errors. MATERIALS AND METHODS Peripapillary RNFL circle scans and macular 3-dimensional scans of consecutive cases imaged with SDOCT (RS-3000 Advance; Nidek, Gamagori, Japan) were retrospectively reviewed by a glaucoma specialist. Images with signal strength index (SSI)

High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied.We established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography.Our PEG-column method demonstrated high reproducibility (coefficient of variation3.52%) and linearity up to 15mg/dl for apoE-rich HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rThe PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis.

Purpose To evaluate the morphological characteristics of posterior corneal regions including keratic precipitates in eyes with cytomegalovirus (CMV) corneal endotheliitis using anterior segment spectral domain optical coherence tomography (SD-OCT). Methods Thirteen eyes of 13 patients with polymerase chain reaction-proven CMV corneal endotheliitis were included in this study. Slit-lamp images and anterior segment SD-OCT images of the posterior cornea were obtained to analyze the clinical characteristics of corneal structures and keratic precipitates. Morphological changes in the posterior cornea throughout the course of an antiviral treatment were also investigated. Results Anterior SD-OCT images showed protruding structures at the posterior cornea. These protruding structures exhibited dendritic, dome-shaped, quadrangular, or saw-tooth appearance, and reflectivity of these structures was high. Reflectivity of posterior corneal images including the endothelium and deep stromal corneal regions were also high (76.9%). Because corneal inflammation and corneal edema improved, the protruding structures and high-intensity regions of posterior corneal images were resolved after a course of antiviral treatment. Conclusions The anterior segment SD-OCT examination represents a useful noninvasive alternative to diagnose and monitor CMV corneal endotheliitis.

A deep-learning (DL) based noise reduction algorithm, in combination with a vessel shadow compensation method and a three-dimensional (3D) segmentation technique, has been developed to achieve, to the authors best knowledge, the first automatic segmentation of the anterior surface of the lamina cribrosa (LC) in volumetric ophthalmic optical coherence tomography (OCT) scans. The present DL-based OCT noise reduction algorithm was trained without the need of noise-free ground truth images by utilizing the latest development in deep learning of de-noising from single noisy images, and was demonstrated to be able to cover more locations in the retina and disease cases of different types to achieve high robustness. Compared with the original single OCT images, a 6.6 dB improvement in peak signal-to-noise ratio and a 0.65 improvement in the structural similarity index were achieved. The vessel shadow compensation method analyzes the energy profile in each A-line and automatically compensates the pixel intensity of locations underneath the detected blood vessel. Combining the noise reduction algorithm and the shadow compensation and contrast enhancement technique, medical experts were able to identify the anterior surface of the LC in 98.3% of the OCT images. The 3D segmentation algorithm employs a two-round procedure based on gradients information and information from neighboring images. An accuracy of 90.6% was achieved in a validation study involving 180 individual B-scans from 36 subjects, compared to 64.4% in raw images. This imaging and analysis strategy enables the first automatic complete view of the anterior LC surface, to the authors best knowledge, which may have the potentials in new LC parameters development for glaucoma diagnosis and management.

The non-alcoholic steatohepatitis (NASH) increases the cardiovascular risk regardless of risk factors in metabolic syndrome. The stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr), fed a high-fat and -cholesterol (HFC) diet and administered Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) presented NASH and cardiovascular disease. However, the intermediary factors between NASH and cardiovascular risk are still unknown. We investigated whether bile acids (BAs) play an intermediary role between NASH and cardiovascular disease in SHRSP5/Dmcr rats. SHRSP5/Dmcr rats divided into 2 groups were fed an SP (non-NASH group, n=7) or HFC diet (NASH group, n=10) for 8 weeks. L-NAME was administered intraperitoneally in the final 2 weeks. In the NASH group, total BA levels were increased in both serum and liver; they aggravated the endothelial dysfunction in aorta, which is the first step to atherosclerosis, and activated the gene expression levels of cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1) in coronary artery. In particular, the nuclear factor-kappa B (NFkB) was increased in the NASH group in the coronary endothelial cells activated by high BA levels. We demonstrated that liver BAs aggravated steatosis and fibrosis and serum BA accelerated arteriosclerosis and ischemic heart disease via the classical pathway of NFkB in the endothelial cells. BA metabolism disorder may be an intermediary factor between NASH and cardiovascular risk in SHRSP5/Dmcr rats.

Using recently developed diagnostic and treatment methods, we successfully diagnosed and treated a case of subclavian steal syndrome. Syncope and left upper arm weakness suggested ischemia of the cerebral and left upper arm circulation. Volume-plethysmographic blood pressure measurements clarified the differences between the upper arms simultaneously. A high-resolution Doppler instrument revealed a retrograde left vertebral artery waveform, indicating subclavian steal syndrome. Aortography demonstrated proximal left subclavian artery occlusion. The patient was treated with stent implantation via a femoral approach using the latest equipment. Advances in diagnostic and treatment approaches for this syndrome are reviewed in connection with this case. Summary : We present a case of subclavian steal syndrome successfully diagnosed using the latest technology and treated with stent implantation. The syndrome and its treatment are reviewed.

The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (Pcombined = 4.3 × 10−5, OR = 0.72, I2 = 0). Additionally, we replicated the association of one known SNP, rs33912345 (Pcombined = 0.0061, OR = 0.69, I2 = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (Pcombined = 0.017, OR = 0.70, I2 = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (Pcombined

Author(s): Miki, Atsuya; Ikuno, Yasushi; Weinreb, Robert N; Yokoyama, Junko; Asai, Tomoko; Usui, Shinichi; Nishida, Kohji | Abstract: ObjectiveTo measure the parapapillary atrophy (PPA) area in en face images obtained with swept-source optical coherence tomography (SS-OCT), and to evaluate its relationship to glaucoma, myopia, and age in non-highly myopic subjects.DesignRetrospective, cross-sectional study.ParticipantsFifty eyes of 30 subjects with open-angle glaucoma (G group) and forty-three eyes of 26 healthy control subjects (C group). Eyes with high myopia (spherical equivalent refractive error ≤ -8 diopters or axial length ≥ 26.5 mm) were excluded.MethodsMean age ± standard deviation was 59.9 ± 12.4 years. The beta zone and the gamma zone PPA areas were measured in en face images reconstructed from three-dimensional SS-OCT images. Relationship between the PPA areas and patient characteristics such as glaucoma, axial length, and age was statistically evaluated using multivariate mixed-effects models.Main outcome measuresAreas of the beta zone and the gamma zone PPA measured on en face OCT images.ResultsAverage ± standard deviation area of the beta and the gamma zone was 0.64 ± 0.79 and 0.16 ± 0.30 mm2, respectively. In multivariate models, the gamma zone significantly correlated with axial length (P = 0.001) but not with glaucoma (P = 0.944). In contrast, the beta zone significantly correlated with age (P = 0.0249) and glaucoma (P = 0.014).ConclusionsEn face images reconstructed from 3D SS-OCT data facilitated measurements of the beta and the gamma PPA zones even in eyes with optic disc distortion. The OCT-defined beta zone is associated with glaucoma and age, whereas the gamma zone correlated with myopia but not with glaucoma. This study confirmed the clinical usefulness of OCT-based classification of the PPA zones in distinguishing glaucomatous damage of the optic nerve from myopic damage in non-highly myopic eyes.

In this paper, we introduce a new estimation method for total creatine phosphokinase release based on a physiological model of the serum creatine phosphokinase (CPK) activity change that can be used to estimate the total CPK release accurately, as early as possible, without frequent blood sampling. The physiological model and a new calculation method were applied to the serum CPK activity change of patients who suffered acute myocardial infarction (AMI). According to the results, the physiological model showed good agreement with the serum CPK activity change and the estimated value of the total CPK release also agreed well with that calculated using the conventional technique with clinically acceptable accuracy.

Background In the treatment of bifurcation lesions, routine stenting of both branches has thus far failed to demonstrate a clear clinical advantage over a provisional one-stent strategy. On the other hand, large scale data evaluating different stent types for clinical outcomes after one-stent treatment with final kissing inflation (FKI) of bifurcation lesions is also limited. This prospective study evaluated the clinical and angiographic outcomes of paclitaxel-eluting stents (PES) vs. sirolimus-eluting stents (SES) in single crossover main branch stenting followed by FKI in patients with bifurcation lesions. Methods We randomized 800 patients with single bifurcation lesions to PES (n=400) and SES (n=400) groups. Results Crossover rates to the two-stent strategy were low in both groups (PES 1.5%, SES 2.8%; p=0.23). At 1year, there was no significant difference in the primary endpoint of this study, target lesion revascularization rate (PES 3.8%, SES 3.2%, hazard ratio 0.83; 95% confidence interval 0.39 to 1.76; p=0.62). Stent thrombosis occurred in only 1 case in the SES group after 282days. At 9months, a total of 593 patients underwent quantitative coronary measurement. The main branch restenosis rate in the PES group was significantly higher than that of the SES group (PES 12.2%, SES 5.5%; p=0.004), however both groups exhibited similar high side branch restenosis rates (PES 17.2%, SES 19.3%; p=0.6). Conclusions In patients with bifurcation lesions, a single stent strategy using PES and SES with FKI indicated similar 1year clinical outcomes and safety profiles.

To evaluate the efficacy of selective laser trabeculoplasty (SLT) for patients with open-angle glaucoma receiving maximal-tolerable medical therapy.Consecutive patients with open-angle glaucoma who were followed up for at least 1 year after SLT were retrospectively evaluated. The effectiveness was assessed using Kaplan-Meier survival analysis with 2 criteria for failure: (1) intraocular pressure (IOP) equal to or more than baseline; and (2)20% reduction from baseline, on 2 consecutive visits. Those 2 failure criteria also included loss of light perception, reoperation of SLT, and glaucoma surgery. Influence of baseline factors on success were assessed using mixed-effects Cox proportional hazard models.Seventy-five eyes [39 primary open-angle glaucoma, 23 exfoliation glaucoma, and 13 secondary open-angle glaucoma (SOAG)] of 59 patients (21 females) aged 65.5±15.9 (mean±SD) were included. Preoperative mean IOP was 23.3±6.5 mm Hg with 3.4±1.3 IOP lowering medications. The overall success ratio at the end of study period was 45.3% by criterion 1 and 14.2% by criterion 2. The success ratio by criterion 1 and 2 was 61.1% and 21.7% in primary open-angle glaucoma, 29.3% and 14.5% in exfoliation glaucoma, and 15.4% and 7.7% in SOAG, respectively. Higher preoperative IOP and diagnosis of SOAG were significantly associated with treatment failure (P0.01 and 0.04, respectively).One-year efficacy of SLT in controlling IOP was very limited in patients with maximal-tolerable medical therapy. Types of glaucoma and preoperative IOP were significant prognostic factors for treatment success.

Recent studies have demonstrated the important role of immune molecules in the development of neuronal circuitry and synaptic plasticity. We have detected the presence of FcγRllB protein in parvalbumin- containing inhibitory interneurons (PV neurons). In the present study, we examined the appearance of PV neurons in the barrel cortex and the effect of sensory deprivation in FcγRllB-deficient mice (FcγRllB-/-) and wild-type mice. There was no substantial difference in the appearance of PV neurons in the developing barrel cortex between FcγRllB-/- and wild-type mice. Sensory deprivation from immediately after birth (P0) or P7 to P12-P14 induced an increase in PV neurons. In contrast, sensory deprivation from P7 or P14 to P28, but not from P21 to P28, decreased PV neurons in wild-type mice. However, sensory deprivation from P0 or P7 to P12-P14 did not increase PV neurons and sensory deprivation from P7 or P14 to P28 did not decrease or only modestly decreased PV neurons in FcγRllB-/- mice. The results indicate that expression of PV is regulated by sensory experience and the second and third postnatal weeks are a sensitive period for sensory deprivation, and suggest that FcγRllB contributes to sensory experience-regulated expression of PV.

The JSFR is a commercial sodium-cooled fast reactor that has been studied in the Fast Reactor Cycle Technology Development (FaCT) project since 2006. For JSFR fuel handling, various fuel-handling systems (FHSs) were investigated, and an advanced FHS with an ex-vessel storage tank (EVST) was selected. This paper summarizes the various FHS concepts and comparisons among those concepts. In the reference system, spent-fuel subassemblies are cooled in the EVST before transfer to the spent-fuel storage pool. The other FHS concepts investigated are evolutional FHSs without an EVST. The result has indicated that the construction cost of the evolutional systems does not reduce the construction cost dramatically, which is mainly due to additional safety measures that required higher decay heat handling in a gas atmosphere and separated fresh and failed fuel storage. From an economics point of view, a longer plant outage of the evolutional systems offsets its advantage of the lower construction cost. Based on the results of this comparative study, JSFR selected the FHS with an EVST.

Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.

To investigate the relationship between relative lens position (RLP) and appositional closure in eyes with narrow angles.Ultrasound biomicroscopy (UBM) was used to measure anterior chamber depth (ACD) and lens thickness (LT), and the IOLMaster to measure axial length (AL). The number of quadrants with appositional closure was assessed by UBM under dark conditions. The RLP was calculated thus: RLP = 10 × (ACD + 0.5 LT) /AL.This study comprised 30 consecutive patients (30 eyes) with narrow-angle eyes defined as Shaffer grade 2 or lower and without peripheral anterior synechiae (24 women, 6 men; mean age ± SD, 67.3 ± 10.4 years; range, 42-87 years). Under dark conditions, 66.7% of the eyes with narrow angles showed appositional closure in at least one quadrant. Of the various ocular biometric parameters, only the RLP significantly decreased with appositional closure in at least one quadrant (P = 0.005).A decrease in the RLP can be predictive of appositional closure for narrow-angle eyes under dark conditions.

Two constituents of bile, bilirubin and tauroursodeoxycholic acid (TUDCA), have antioxidant activity. However, bilirubin can also cause damage to some neurons and glial cells, particularly immature neurons. In this study, we tested the effects of bilirubin and TUDCA in two models in which oxidative stress contributes to photoreceptor cell death, prolonged light exposure and rd10+/+ mice. In albino BALB/c mice, intraperitoneal injection of 5 mg/kg of bilirubin or 500 mg/kg of TUDCA prior to exposure to 5000 lux of white light for 8 h significantly reduced loss of rod and cone function assessed by electroretinograms. Both treatments also reduced light-induced accumulation of superoxide radicals in the outer retina, rod cell death assessed by outer nuclear layer thickness, and disruption of cone inner and outer segments. In rd10+/+ mice, intraperitoneal injections of 5 or 50 mg/kg of bilirubin or 500 mg/kg of TUDCA every 3 days starting at postnatal day (P) 6, caused significant preservation of cone cell number and cone function at P50. Rods were not protected at P50, but both bilirubin and TUDCA provided modest preservation of outer nuclear layer thickness and rod function at P30. These data suggest that correlation of serum bilirubin levels with rate of vision loss in patients with retinitis pigmentosa could provide a useful strategy to test the hypothesis that cones die from oxidative damage in patients with retinitis pigmentosa. If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials.

Introduction The optimal combination treatment for hypertension has not been established. We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers (ARBs) on the augmentation index (AI), as a marker of arterial stiffness and wave reflection, in hypertensive patients. Methods Thirty-seven patients treated with ARBs were randomly allocated to either of the 2 groups receiving an ARB plus azelnidipine (AZ group) or trichlormethiazide (TCM group). Changes in brachial blood pressure (BP), AI, high-sensitive C-reactive protein (hsCRP), and serum asymmetric dimethylarginine, as an endogenous nitric oxide synthase inhibitor, were determined. Results Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly; however, after adjustment for baseline covariates, the extent of the reduction in AI (%) in the AZ group was significantly greater than in the TCM group (between-group difference was 3.2; 95%CI: 0.2–6.3; P = 0.03). The reduction of high-sensitive C-reactive protein (mg/L) and serum asymmetric dimethylarginine ( μ mol/L) was significantly greater in the AZ group than in the TCM group (between-group difference was 0.18 and 0.05; 95%CI: −0.01 to 0.36 and −0.01 to 0.11; P = 0.04 and 0.02, respectively). Further, when patients were analyzed according to age younger than 60 years or older than 60 years, the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group. Conclusion The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide.

Retinitis pigmentosa (RP) is a collection of diseases in which rod photoreceptors die from a variety of mutations. After rods die, the level of tissue oxygen in the outer retina becomes elevated and there is progressive oxidative damage to cones that ultimately triggers apoptosis. In this study, we investigated the hypothesis that NADPH oxidase and/or xanthine oxidase serve as critical intermediaries between increased tissue oxygen and the generation of excessive reactive oxygen species that cause oxidative damage to cones. Apocynin, a blocker of NADPH oxidase, but not allopurinol, a blocker of xanthine oxidase, markedly reduced the superoxide radicals visualized by hydroethidine in the outer retina in the retinal degeneration-1 (rd1+/+) model of RP. Compared to rd1+/+ mice treated with vehicle, those treated with apocynin, but not those treated with allopurinol, had significantly less oxidative damage in the retina measured by ELISA for carbonyl adducts. Apocynin-treated, but not allopurinol-treated, rd1+/+ mice had preservation of cone cell density, increased mRNA levels for m- and s-cone opsin, and increased mean photopic b-wave amplitude. In Q344ter mice, a model of dominant RP in which mutant rhodopsin is expressed, apocynin treatment preserved photopic electroretinogram b-wave amplitude compared to vehicle-treated controls. These data indicate that NADPH oxidase, but not xanthine oxidase, plays a critical role in generation of the oxidative stress that leads to cone cell death in RP and inhibition of NADPH oxidase provides a new treatment strategy.

Oxidative and nitrosative damage are major contributors to cone cell death in retinitis pigmentosa (RP). In this study, we explored the effects of augmenting components of the endogenous antioxidant defense system in models of RP, rd1, and rd10 mice. Unexpectedly, overexpression of superoxide dismutase 1 (SOD1) in rd1 mice increased oxidative damage and accelerated cone cell death. With an elaborate mating scheme, genetically engineered rd10 mice with either inducible expression of SOD2, Catalase, or both in photoreceptor mitochondria were generated. Littermates with the same genetic background that did not have increased expression of SOD2 nor Catalase provided ideal controls. Coexpression of SOD2 and Catalase, but not either alone, significantly reduced oxidative damage in the retinas of postnatal day (P) 50 rd10 mice as measured by protein carbonyl content. Cone density was significantly greater in P50 rd10 mice with coexpression of SOD2 and Catalase together than rd10 mice that expressed SOD2 or Catalase alone, or expressed neither. Coexpression of SOD2 and Catalase in rd10 mice did not slow rod cell death. These data support the concept of bolstering the endogenous antioxidant defense system as a gene-based treatment strategy for RP, and also indicate that coexpression of multiple components may be needed.

Background Activin A, a member of the transforming growth factor-β cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI). Methods The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14. Results Activin A levels before PCI in AMI patients (557 ± 255 pg/ml) showed a significantly higher value than those in AP patients (364 ± 159 pg/ml) and control subjects (316 ± 144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r = 0.48, p = 0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK. Conclusions The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.

Background Serum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL. Methods We determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance. Results In simple regression analyses, RBP4 levels had significant correlations with total cholesterol ( r = 0.354, P = 0.029), LDL-cholesterol ( r = 0.396, P = 0.014), and sdLDL-cholesterol ( r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol ( r = 0.402, P = 0.012), LDL-cholesterol ( r = 0.627, P r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient ( s ) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R 2 = 0.240), whereas RBP4 ( s = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R 2 = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels. Conclusions We showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.

Objectives To evaluate the gel permeation high-performance liquid chromatography (GP-HPLC) method for determination of triglyceride (TG) levels in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Design and methods The GP-HPLC and the ultracentrifugation(UC)/precipitation methods were used and compared. Results There was no significant difference in measured levels of LDL-triglyceride between the two methods, but the HDL-triglyceride levels measured by the GP-HPLC technique were significantly higher than the UC/precipitation one (145 ± 47 mg/L and 121 ± 45 mg/L respectively, n = 38, p Conclusions A GP-HPLC technique provides LDL-TG levels comparable to those obtained by the UC/precipitation method.

The main purpose of this study was to evaluate an HPLC method for LDL-cholesterol determination in the presence of abnormal lipoproteins.We compared LDL-cholesterol levels obtained by HPLC (HPLC-LDL), Friedewald (F-LDL), and beta-quantification (BQ-LDL) methods on 47 healthy volunteers and 50 outpatients with lipid disorders, including apolipoprotein E2/2 phenotype, cholesteryl ester transfer protein deficiency and lipoprotein lipase deficiency.For the control group (n=50), the HPLC-LDL and the F-LDL correlated highly with the BQ-LDL (r=0.984 and 0.969, respectively), but the HPLC-LDL was lower than the BQ-LDL (mean bias: -4.0%, P0.001). For the subjects with lipoprotein abnormalities, significant biases were found in HPLC-LDL for the hypertriglyceridemia (+25%, n=17, P0.01), the hyper HDL (-15.2%, n=10, P0.01) and the hyper lipoprotein(a) groups (-13.4%, n=12, P0.001). The F-LDL was significantly higher than the BQ-LDL in the apolipoprotein E2/2 subjects (+92%, n=8, P0.001), but not significantly different in other subjects with triglycerides4000 mg/l.There were several discrepancies in LDL-cholesterol levels determined by the HPLC and the BQ methods in samples with lipoprotein abnormalities. However, the HPLC method can be useful and informative for analysis of abnormal lipoproteins.

Retinitis pigmentosa (RP) is a group of diseases in which many different mutations cause rod photoreceptor cells to die and then gradually cone photoreceptors die due to progressive oxidative damage. In this study, we have shown that peroxynitrite-induced nitrosative damage also occurs. In the rd1 mouse model of RP, there was increased staining for S-nitrosocysteine and nitrotyrosine protein adducts that are generated by peroxynitrite. Peroxynitrite is generated from nitric oxide (NO) and superoxide radicals. After degeneration of rods, injection of hydroethidine resulted in strong fluorescence in the retina of rd1 mice, indicating high levels of superoxide radicals, and this was reduced, as was nitrotyrosine staining, by apocynin, suggesting that overaction of NADP(H) oxidase is at least partially responsible. Treatment of rd1 mice with a mixture of nitric oxide synthase (NOS) inhibitors markedly reduced S-nitrosocysteine and nitrotyrosine staining and significantly increased cone survival, indicating that NO-derived peroxynitrite contributes to cone cell death. Treatment with 7-nitroindazole, a relatively specific inhibitor of neuronal NOS, also significantly reduced cone cell death, but aminoguanidine, a relatively specific inhibitor of inducible NOS, did not. These data suggest that NO generated by neuronal NOS exacerbates oxidative damage to cones in RP and that combined therapy to reduce NO and oxidative stress should be considered.