Publications by authors named "Minoru Furuta"

38 Publications

Clinical features and symptoms of IgG4-related ophthalmic disease: a multicenter study.

Jpn J Ophthalmol 2021 Sep 19;65(5):651-656. Epub 2021 Jun 19.

Kanazawa University, Kanazawa, Japan.

Purpose: The aim of this study was to elucidate the clinical features and symptoms of IgG4-related ophthalmic disease (IgG4-ROD).

Study Design: Retrospective, multicenter study.

Methods: The medical charts of 378 patients with IgG4-ROD diagnosed at 9 hospitals in Japan were reviewed. The demographic profiles, clinical findings, and ocular symptoms of the patients were analyzed.

Results: On the basis of the diagnostic criteria for IgG4-ROD, the diagnosis was definite in 261 patients (69%), probable in 45 patients (12%), and possible in 72 patients (19%). The patients' mean age at the time of diagnosis was 60.6 ± 13.9 years; 195 (52%) were male. The mean IgG4 serum level at the time of the initial diagnosis was 578.9 mg/dL. Imaging studies showed pathologic lesions as follows: lesions in the lacrimal glands (86%), extraocular muscles (21%), trigeminal nerve (20%), and eyelids (12%); isolated orbital mass (11%); diffuse orbital lesion (8%); lesion in the perioptic nerve (8%); and lesion in the sclera (1%). The ophthalmic symptoms included dry eye (22%), diplopia (20%), decreased vision (8%), and visual field defects (5%). IgG4-ROD with extraocular lesions was observed in 182 patients (48%).

Conclusion: Although the lacrimal glands are well known to be the major pathologic site of IgG4-ROD, various ocular tissues can be affected and cause ophthalmic symptoms including visual loss.
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http://dx.doi.org/10.1007/s10384-021-00847-3DOI Listing
September 2021

White Paper on Ophthalmic Imaging for Choroidal Nevus Identification and Transformation into Melanoma.

Transl Vis Sci Technol 2021 02;10(2):24

Department of Ophthalmology, Ophthalmology Innovation Program, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process.

Methods: White paper.

Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photography, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI.

Conclusions: AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma.

Translational Relevance: Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes.
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http://dx.doi.org/10.1167/tvst.10.2.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900849PMC
February 2021

Hybrid Three-Dimensional Visualization of Choroidal Vasculature Imaged by Swept-Source Optical Coherence Tomography.

Transl Vis Sci Technol 2019 Sep 22;8(5):31. Epub 2019 Oct 22.

Department of Systems Neuroscience, Fukushima Medical University, Fukushima, Japan.

Purpose: To create hybrid three-dimensional (3D) models of the choroidal vasculature from swept-source optical coherence tomography (SS-OCT) angiography images and to evaluate the model's characteristics.

Methods: This study used prospective, noncomparative case series, including 21 eyes of 21 healthy individuals. The 6 × 6-mm macular area was imaged repeatedly to obtain two cube image sets. Images from structural OCT (OCT-S) and OCT angiography (OCT-A) were exported. After vessel-like structures segmentation from the inverted black and white OCT-S images and the OCT-A images, both types of images were reconstructed in a 3D model. The volumes of the outer choroid and the choroidal vessels were measured after thresholding. The similarities of the segmented choroidal vessels (between OCT-S and OCT-A) and between repeatedly acquired images were measured.

Results: Mean vessel volume was 2.227 mm (29% of the outer choroidal volume) in OCT-S and 0.848 (11%) in OCT-A when measured after removal of the choriocapillaris equivalent volume. Three percent of the vessel volume in OCT-S and 8.4% of that in OCT-A overlapped. The Dice similarity coefficient of vessel volumes in repeated images from the same individual was 0.863 in OCT-S and 0.485 in OCT-A. The ratio of vessel volume to the outer choroidal volume was invariant in OCT-S but increased in OCT-A in the eyes with long axial length.

Conclusions: Hybrid 3D vascular models of the choroidal vasculature were reconstructed from OCT-S and OCT-A. The new models should prove useful for volumetric analysis of the choroid.

Translational Relevance: Hybrid 3D models of the choroidal vasculature enable volumetric analysis and facilitate morphologic evaluation.
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http://dx.doi.org/10.1167/tvst.8.5.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807678PMC
September 2019

Morphometrical evaluation of the choriocapillaris imaged by swept-source optical coherence tomography angiography.

Clin Ophthalmol 2018 5;12:2267-2276. Epub 2018 Nov 5.

Department of Ophthalmology, Fukushima Medical University, Fukushima, Japan,

Purpose: To assess the reproducibility of quantitative morphometrical evaluation of the choriocapillaris imaged with swept-source optical coherence tomography angiography (SS-OCTA).

Subjects And Methods: This observational, cross-sectional case series included 35 eyes of healthy individuals and 32 eyes of 32 patients. Two images of the fovea were taken using SS-OCTA with 3×3 mm squares. Images of the choriocapillaris within 800×800 pixel squares centered at the fovea were analyzed morphometrically using open-source software "AngioTool" that applies a Gaussian recursive filter and multiscale Hessian enhancement. This program's vessel thickness and intensity parameters can be changed to aid vessel detection. We measured the pairs of images per eye with different parameter sets and calculated the intraclass correlation (ICC) for the morphometrical results. After determining the parameters that produced high reproducibility, we evaluated regional variations in 800×800 pixel mm squares within the fovea.

Results: The ICCs for vessel area, total vessel length, vessel diameter index, and mean lacunarity were over 0.9 using the parameters of "vessel thickness" 3-4 and intensity 15 in the group including all subjects. When measurements were performed using these same parameter values, the vessel density and mean vessel diameter index were 60.5% and 19.1±0.389, respectively. Vessel density, vessel length, vessel diameter index, and mean lacunarity did not change significantly within an 800×800 pixel square centered at the fovea except for the 200×200 pixel square at the foveal center.

Conclusion: SS-OCTA images of the choriocapillaris can be measured with high reproducibility by morphometrical evaluation using open-source software with multiscale Hessian enhancement. Such automated morphometric analysis can provide an objective evaluation of the choriocapillaris.
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http://dx.doi.org/10.2147/OPTH.S179634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223397PMC
November 2018

Near-infrared and short-wave autofluorescence in ocular specimens.

Jpn J Ophthalmol 2018 Sep 2;62(5):605-613. Epub 2018 Aug 2.

Department of Ophthalmology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima City, Fukushima, 960-1295, Japan.

Purpose: To determine histopathologic characteristics of near-infrared autofluorescence (NIR-AF) and short-wave autofluorescence (SW-AF) in ocular tissue.

Study Design: Retrospective study.

Methods: Unstained specimens from four enucleated eyes with uveal melanoma were prepared for evaluation by fluorescence microscopy. The filter settings for SW-AF were 450-490 nm for excitation, 500-550 nm for emission and for NIR-AF 672.5-747.5 nm and 765-855 nm respectively.

Results: Hyper-SW-AF was detected in the cornea, crystalline lens, anterior border layer of the iris, basement membrane of the iris posterior epithelium, retinal pigment epithelium (RPE), Bruch's membrane, and sclera. Hyper-NIR-AF was detected in pigmented tissues, i.e., iris anterior border layer, iris posterior epithelium, ciliary pigmented epithelium, RPE, pigmented cells in the choroid and pigmented cells in the melanoma tumoral masses. The iris anterior border layer had hyper-SW-AF and hyper-NIR-AF with low magnification. The cells on the iris surface were with hyper-SW-AF; under the iris surface cells with hyper-NIR-AF were detected with high magnification. Both hyper-SW-AF and hyper-NIR-AF were in RPE cells. Pigmented cells with hyper-NIR-AF in other uveal tissues did not have hyper-SW-AF. The pigmented cells in the melanoma tumoral masses had very weak NIR-AF.

Conclusions: NIR-AF was seen in the ocular pigmented tissues. The only pigmented tissue with both hyper-SW-AF and hyper-NIR-AF was RPE, the combination of which might help interpret the cellular components of fundus lesions.
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http://dx.doi.org/10.1007/s10384-018-0614-5DOI Listing
September 2018

American Joint Committee on Cancer Classification of Uveal Melanoma (Anatomic Stage) Predicts Prognosis in 7,731 Patients: The 2013 Zimmerman Lecture.

Ophthalmology 2015 Jun 24;122(6):1180-6. Epub 2015 Mar 24.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To analyze the clinical features and prognosis of posterior uveal melanoma based on the American Joint Committee on Cancer (AJCC) (7th edition) tumor staging.

Design: Retrospective interventional case series.

Participants: A total of 7731 patients.

Methods: Uveal melanoma management.

Main Outcome Measures: Melanoma-related metastasis and death.

Results: Of 7731 patients with posterior uveal (ciliary body and choroidal) melanoma, the AJCC tumor staging was stage I in 2767 (36%), stage II in 3735 (48%), stage III in 1220 (16%), and stage IV in 9 (<1%). Based on tumor staging (I, II, III, and IV), features that showed significant increase with tumor staging included age at presentation (57, 58, 60, 60 years) (P < 0.001), tumor base (8, 12, 17, 17 mm) (P < 0.001), tumor thickness (2.9, 6.0, 10.1, 10.2 mm) (P < 0.001), distance to optic disc (3, 5, 5, 5 mm) (P < 0.001), distance to foveola (3, 5, 5, 5 mm) (P < 0.001), mushroom configuration (6%, 24%, 34%, 33%) (P < 0.001), plateau configuration (3%, 4%, 7%, 11%) (P < 0.001), tumor pigmentation (48%, 53%, 69%, 78%) (P < 0.001), and extraocular extension (0%, 1%, 11%, 22%) (P < 0.001). After therapy, Kaplan-Meier estimates of metastasis at 1, 5, 10, and 20 years were <1%, 5%, 12%, and 20% for stage I, 2%; 17%, 29%, and 44% for stage II; 6%, 44%, 61%, and 73% for stage III, and 100% by 1 year for stage IV. Kaplan-Meier estimates of death at 1, 5, 10, and 20 years were <1%, 3%, 6%, and 8% for stage I; <1%, 9%, 15%, and 24% for stage II; 3%, 27%, 39%, and 53% for stage III, and 100% by 1 year for stage IV. Compared with stage I, the hazard ratio for metastasis/death was 3.1/3.1 for stage II and 9.3/10.1 for stage III.

Conclusions: Compared with uveal melanoma classified as AJCC stage I, the rate of metastasis/death was 3 times greater for stage II, 9 to 10 times greater for stage III, and further greater for stage IV. Early detection of posterior uveal melanoma, at a point when the tumor is small, can be lifesaving.
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http://dx.doi.org/10.1016/j.ophtha.2015.01.026DOI Listing
June 2015

Effect of protoconized therapy for renal anemia on adverse events of patients with maintenance hemodialysis.

Int J Artif Organs 2014 Dec 29;37(12):865-74. Epub 2014 Nov 29.

Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Hyogo - Japan.

Purpose: We evaluate the effect of the protoconized anemia therapy on adverse events using the Hb and ferritin levels of individual patients undergoing maintenance hemodialysis (MHD).

Methods: Design: A randomized, parallel group, multi-center study.

Patients: Two hundred sixty-six MHD patients. Intervention group: The doses of erythropoietin, iron, and vitamin C were adjusted every month based on the ferritin and hemoglobin (Hb) levels according to the protocol. Non-intervention group: The attending physician determined the doses of erythropoietin and iron.

Results: The maintenance rate of target Hb and ferritin levels were significantly higher in the Intervention group than in the Non-intervention group. The frequency of hospitalization was significantly lower for patients with a higher maintenance rate of target Hb levels than for those with a lower maintenance rate.

Conclusions: Using an anemia treatment protocol according to the individual Hb and ferritin levels of hemodialysis patients might stabilize the Hb and ferritin levels, which in turn could contribute to the lower frequency of adverse events in MHD patients.
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http://dx.doi.org/10.5301/ijao.5000370DOI Listing
December 2014

Hemodialysis restored iron distribution that was sequestered in the spleen by bilateral nephrectomy.

Am J Physiol Renal Physiol 2014 Jun 16;306(12):F1393-9. Epub 2014 Apr 16.

Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; and.

Acute kidney injury (AKI) is associated with dysregulated iron metabolism, which may play a significant role in cellular injury. The effect of hemodialysis (HD) on iron metabolism in AKI therapy has not been well defined. The effects of HD on iron parameters were tested in control rats and bilateral nephrectomy (BNx) rats. The BNx rats were divided into the following three groups: 1) the sham-operated group (BNx-Sham), 2) the BNx group, and 3) the HD group (BNx-HD), which received HD therapy 40-45 h after BNx. Sections of the liver or spleen were stained with Berlin blue to examine the accumulation of iron. The mRNA levels of hepcidin and ferroportin 1 in the spleen and liver were also quantified using RT-PCR. In the BNx group, the plasma iron and hematocrit levels were decreased, and hepcidin levels were increased. The iron staining in the spleen in the BNx group was significantly more intense than that in the BNx-Sham group; however, after an HD session, splenic iron staining diminished to the level of the sham group along with an increase in plasma iron and a decrease in hepcidin. BNx moved iron from hemoglobin and the plasma to the spleen, which is associated with an increase in plasma hepcidin. A single HD session accelerated the release of iron from the spleen, and the increased plasma iron was linked to the removal of hepcidin. Our data suggested that hepcidin might dynamically modulate the iron metabolism in BNx as well as in HD.
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http://dx.doi.org/10.1152/ajprenal.00685.2012DOI Listing
June 2014

Morphologic changes of the fovea and visual acuity associated with retinal detachment secondary to circumscribed choroidal hemangioma.

Saudi J Ophthalmol 2013 Jul;27(3):209-13

Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Purpose: To clarify and review the early and late morphologic changes of the macula associating with visual loss in patients with subfoveal fluid secondary to extrafoveal circumscribed choroidal hemangiomas.

Methods: Previously six non-treated eyes of six patients with subfoveal retinal detachment secondary to extrafoveal circumscribed choroidal hemangioma were included. Visual acuity (VA), duration of visual symptoms, color fundus photography, optical coherence tomography (OCT), fundus autofluorescence, and fluorescein angiography (FA) were evaluated.

Results: The mean patient age was 58 years (range, 25-78). The VA and duration of symptoms in each patient was 1.2 (3 days), 0.6 (1 week), 0.4 (3 months), 0.5 (6 months), 0.02 (12 months), and 0.01 (8 years), respectively. Three patients with symptoms for less than 3 months did not have retinal pigment epithelial (RPE) alterations, retinal edema, or thinning of the retinal structure in the fovea. A patient with symptoms for 3 months had subfoveal deposits underneath the detached neurosensory retina with foveal hyperautofluorescence. Two patients with symptoms exceeding 12 months had highly affected RPE and cystoid macular degeneration.

Conclusions: The VA was affected in patients with longer visual symptoms, and there are some changes in the retina and RPE in the fovea by FA and OCT. Persistent subretinal fluid secondary to choroidal hemangiomas may result in pathologic changes in the neurosensory retina.
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http://dx.doi.org/10.1016/j.sjopt.2013.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770212PMC
July 2013

The removal of serum hepcidin by different dialysis membranes.

Int J Artif Organs 2013 Oct 2;36(9):633-9. Epub 2013 Aug 2.

Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Seishoukai Aoi Hospital, Hyogo - Japan.

Purpose: Hepcidin has been suspected to be associated with anemia of chronic disease, which is commonly observed in patients with maintenance hemodialysis (MHD). As almost of hepcidin is bounded to protein, it is essential to clarify which kind of dialysis membrane can remove it efficiently.

Methods: Ex vivo study: 50 mL of whole blood from healthy volunteers were circulated for 2 h in a microcircuit with mini-dialyzers (acrylonitrile-co-methallyl sulfonate (AN69) or polysulfone (PS)) without ultrafiltration. We measured hepcidin-25 levels at 0, 60, and 120 min in the blood samples. In vivo study: Blood samples were taken from 28 MHD patients at the start and end of HD sessions with PS or AN69. We measured serum levels of hepcidin 20, 22, and 25 by liquid chromatography tandem mass spectrometry, and also measured serum levels of urea nitrogen (UN), β2microglobulin (MG).

Results: Ex vivo study: Although serum hepcidin 25 levels increased after the ex vivo session with PS, they significantly decreased with AN69. In vivo study: The reduction ratio of β2MG by PS was significantly higher than that of AN69. On the other hand, there was no significant difference in the reduction ratio of hepcidin 20, 22, and 25 between PS and AN69.

Conclusions: Both super-flux PS and AN69 similarly removed hepcidin 20 22, and 25. HD with PS might achieve a high removal ratio of hepcidin by enhanced diffusion performance and an increased clearance of small molecule solutes. On the other hand, AN69 might remove hepcidin by adsorption.
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http://dx.doi.org/10.5301/ijao.5000221DOI Listing
October 2013

American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients.

Ophthalmology 2013 Oct 9;120(10):2066-71. Epub 2013 May 9.

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Dr. Kaliki is in practice at the Ocular Oncology Service, L. V. Prasad Eye Institute, Hyderabad, India. Electronic address:

Purpose: To evaluate the clinical features and prognosis of posterior uveal (ciliary body and choroid) melanoma based on the American Joint Committee on Cancer (AJCC) classification (7th edition) of primary tumor (T).

Design: Retrospective, interventional case series.

Participants: Seven thousand seven hundred thirty-one patients.

Intervention: Ocular management including plaque radiotherapy, enucleation, local resection, or laser therapy.

Main Outcome Measures: Melanoma-related metastasis and death.

Results: Of 7731 patients with posterior uveal melanoma, the AJCC classification based on T was category T1 in 3557 (46%), T2 in 2082 (27%), T3 in 1599 (21%), and T4 in 493 (6%). Based on tumor categories T1, T2, T3, and T4, respectively, features that showed significant increase with tumor category included patient age at presentation (57, 58, 58, and 61 years; P<0.001), tumor base (8, 12, 15, and 20 mm; P<0.001), tumor thickness (3.5, 5.2, 8.9, and 11.4 mm; P<0.001), mushroom configuration (8%, 20%, 38%, and 39%; P<0.001), associated subretinal fluid (64%, 80%, 82%, and 83%; P<0.001), intraocular hemorrhage (5%, 12%, 17%, and 18%; P<0.001), rupture of Bruch's membrane (9%, 24%, 40%, and 40%; P<0.001), and extraocular extension (1%, <1%, 4%, and 12%; P<0.001). After therapy, Kaplan-Meier estimates of metastasis at 5, 10, and 20 years were 8%, 15%, and 25% for category T1, 14%, 25%, and 40% for category T2, 31%, 49%, and 62% for category T3, and 51%, 63%, and 69% for category T4, respectively (P<0.001). Kaplan-Meier estimates of death at 5, 10, and 20 years were 4%, 8%, and 11% for category T1, 8%, 13%, and 24% for category T2, 19%, 27%, and 36% for category T3, and 30%, 43%, and 51% for category T4, respectively (P<0.001). Compared with category T1, the hazard ratio for metastasis and death for T2 was 1.8 and 1.9, respectively, that for T3 was 4.5 and 4.7, respectively, and that for T4 was 8.2 and 8.8, respectively.

Conclusions: Based on the AJCC classification, increasing tumor category was associated with older age, larger tumor, and greater incidence of subretinal fluid, hemorrhage, and extraocular extension. Compared with uveal melanoma classified as T1, the rate of metastasis and death was 2 times greater for T2, 4 times greater for T3, and 8 times greater for T4. The risk for metastasis and death increased 2-fold with each increasing melanoma category.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2013.03.012DOI Listing
October 2013

Diffuse versus nondiffuse small (≤ 3 MM thickness) choroidal melanoma: comparative analysis in 1,751 cases. The 2012 F. Phinizy Calhoun lecture.

Retina 2013 Oct;33(9):1763-76

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.

Objective: To determine prognosis of small choroidal melanoma (≤ 3 mm thickness) comparing diffuse versus nondiffuse variants.

Methods: Retrospective chart review of 1,751 patients with small choroidal melanoma classified as diffuse (thickness/base ≤ 20%) versus nondiffuse (thickness/base >20%).

Results: Of 1,751 patients with small choroidal melanoma, 297 (17%) were diffuse and 1,454 (83%) nondiffuse. Features with statistical differences (diffuse vs. nondiffuse) included mean distance to optic disk (3 vs. 4 mm), mean tumor base (12 vs. 8 mm), and mean tumor thickness (1.9 vs. 2.5 mm). Using Kaplan-Meier estimates, melanoma-related metastasis (diffuse vs. nondiffuse) was 8% versus 4% at 5 years, 16% versus 10% at 10 years, and 19% versus 16% at 15 years (P = 0.0344). Melanoma-related death was 6% versus 2% at 5 years, 11% versus 4% at 10 years, and 16% versus 6% at 15 years (P < 0.0001). In the subgroup of thin melanoma 2 mm or less in thickness, melanoma-related death was 7% versus 2% at 5 years, 10% versus 2% at 10 years, and 16% versus 4% at 15 years (P = 0.0077). By multivariate analysis, factors predictive of metastasis from diffuse melanoma included larger tumor basal dimension (P = 0.0027) and plateau/flat tumor configuration (P = 0.0257).

Conclusion: Of 1751 patients with small (≤ 3 mm thickness) choroidal melanoma, those with diffuse tumor show higher probability of metastasis and death than those with nondiffuse tumor. This finding is evident even in the thinnest melanomas (≤ 2 mm thickness).
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http://dx.doi.org/10.1097/IAE.0b013e318285cd52DOI Listing
October 2013

Acetate free citrate-containing dialysate increase intact-PTH and BAP levels in the patients with low intact-PTH.

BMC Nephrol 2013 Jan 18;14:18. Epub 2013 Jan 18.

Department of Internal Medicine Division of kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.

Background: Recently, acetate-free citrate containing dialysate (A(-)D) was developed. We have already reported about the significant effect of A(-)D on metabolic acidosis, anemia, and malnutrition in maintenance hemodialysis (MHD) patients. In this study, we compared the effect of A(-)D and acetate containing dialysate (A(+)D) on serum calcium and intact-parathyroid hormone (int-PTH) levels.

Method: Single session study: Seventeen patients were treated with A(+)D in one session and also treated with A(-)D in another session. Serum levels of pH, HCO3-, total (t)-calcium, ionized (i)-calcium, and int-PTH were evaluated at the beginning and the end of each session. Cross over study: A total of 29 patients with MHD were treated with A(+)D for 4 months, switched to A(-)D for next 4 months, and returned to A(+)D for the final 4 months.

Results: In single session study, serum i-calcium and t-calcium levels significantly increased, and int-PTH levels decreased after HD with A(+)D, whereas HD with A(-)D did not affect iCa and int-PTH. In cross over study, if all patients were analyzed, there was no significant difference in serum int-PTH or bone alkaline phosphatase (BAP) levels during each study period. In contrast, in the patients with low int-PTH (<60 pg/mL), serum levels of int-PTH and BAP were significantly increased during the A(-)D, without significant changes in serum t-calcium or i-calcium levels.

Conclusion: A(-)D containing citrate could affect calcium and PTH levels, and, in 4 month period of crossover study, increased int-PTH levels pararelled with increasing BAP levels, exclusively in MHD patients with low int-PTH levels.
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http://dx.doi.org/10.1186/1471-2369-14-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583681PMC
January 2013

Submacular choroidal neovascularization at the margin of staphyloma in tilted disk syndrome.

Retina 2013 Jan;33(1):71-6

Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Purpose: To clarify the nature of submacular choroidal neovascularization (CNV) and underlying choroidal circulatory disturbances in tilted disk syndrome.

Methods: We retrospectively examined patients with submacular CNV associated with tilted disk syndrome using fluorescein angiography and indocyanine green angiography in this observational case series. The axial lengths were measured by ultrasonography. Eyes with myopia exceeding -6.0 diopters were excluded.

Results: Eleven consecutive eyes (mean patient age ± standard deviation, 60.5 ± 12.1 years) were included. The axial lengths ranged from 21.7 mm to 24.6 mm (mean, 23.61 ± 0.95 mm). Classic CNV in nine eyes and polypoidal choroidal vasculopathy in two eyes developed at the macula along the superior margin of the inferior posterior staphyloma that crossed the macula in all eyes. The superior margin of the inferior posterior staphyloma was hyperfluorescent on fluorescein angiography and hypofluorescent on indocyanine green angiography, with the latter larger than the former. The inferior staphyloma contained fewer and smaller choroidal arteries and veins. During follow-up, the submacular CNV and polypoidal choroidal vasculopathy spontaneously regressed and the subretinal hemorrhage resorbed, leaving a fibrotic scar in eight eyes. Newly developed CNV at the initial no-leakage site on fluorescein angiography developed in one eye and the CNV located in the area of band-shaped hypofluorescence on indocyanine green angiography.

Conclusion: Stretching of the ocular wall might result in occluded choriocapillaris and degeneration of the retinal pigment epithelium. These changes along the border of the inferior posterior staphyloma predispose to submacular CNV and polypoidal choroidal vasculopathy in tilted disk syndrome.
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http://dx.doi.org/10.1097/IAE.0b013e318263ceb4DOI Listing
January 2013

Influence of age on prognosis of young patients with uveal melanoma: a matched retrospective cohort study.

Eur J Ophthalmol 2013 Mar-Apr;23(2):208-16

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; and Ocular Oncology Service, L.V. Prasad Eye Institute, Hyderabad, India.

Purpose: To determine the influence of patient age on life prognosis in patients with uveal melanoma.

Design: Matched retrospective cohort study of 122 patients in each age category (young [≤20 years], mid-adults [21-60 years], older adults [>60 years]).

Results: Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 1%, 8%, and 8% in young; 8%, 11%, and 26% in mid-adults; and 13%, 16%, and 24% in older adults. After exclusion of iris melanoma, Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 2%, 11%, and 18% in young; 9%, 14%, and 21% in mid-adults; and 9%, 34%, and 33% in older adults. Risk factors for metastasis based on multivariate analysis included increasing age in young (p=0.05, hazard ratio [HR] 1.33), male gender in mid-adults (p=0.046, HR 4.23), and larger tumor basal diameter in mid-adults (p=0.002, HR 1.37) and older adults (p=0.001, HR 1.30). After adjusting for tumor diameter, the metastatic rate was lower in young patients compared to mid-adults (0=0.042, HR 3.00) and older adults (p=0.007, HR 4.20).

Conclusions: Younger patient age at the time of diagnosis of uveal melanoma is associated with lower rate of metastasis compared to mid-adults and older adults.
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http://dx.doi.org/10.5301/ejo.5000200DOI Listing
May 2013

Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases.

Retina 2012 Jul;32(7):1363-72

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To evaluate clinical features and life prognosis of uveal melanoma based on age at presentation.

Design: Retrospective, nonrandomized, interventional case series.

Results: Of 8,033 eyes with uveal melanoma, 106 (1%) were in young patients (≤20 years), 4,287 (53%) in mid adults (21-60 years), and 3,640 (45%) in older adults (>60 years). Based on age (young, mid adults, and older adults) at presentation, tumor epicenter was located in iris (21, 4, 2%; P < 0.0001), ciliary body (8, 5, and 7%; P = 0.0225), or choroid (71, 91, and 90%; P < 0.0001). Mean tumor diameter (10.2, 10.8, 11.5 mm; P < 0.0001), mean tumor thickness (5.0, 5.3, 5.7 mm; P < 0.0001), and extraocular extension (1, 2, and 4%; P = 0.0004) increased with age. Kaplan-Meier estimates of tumor-related metastasis at 3, 5, 10, and 20 years were 2%, 9%, 9%, and 20% in young patients (P < 0.011); 6%, 12%, 23%, and 34% in mid adults (P < 0.0001); and 11%, 19%, 28%, and 39% in older adults. Kaplan-Meier estimate of tumor-related death at 3, 5, 10, and 20 years were 0%, 2%, 5%, and 17% in young patients (P = 0.08); 3%, 6%, 11%, and 17% in mid adults (P < 0.001); and 7%, 11%, 16%, and 20% in older adults.

Conclusion: Compared with mid adults and older adults, young patients manifested a higher proportion of iris melanoma. Compared with older adults, young and mid adults showed smaller melanoma basal dimension and lower tumor-related metastasis and death.
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http://dx.doi.org/10.1097/IAE.0b013e31824d09a8DOI Listing
July 2012

Iris melanoma: features and prognosis in 317 children and adults.

J AAPOS 2012 Feb;16(1):10-6

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Purpose: To evaluate iris melanoma in children versus adults.

Methods: Retrospective, nonrandomized clinical case series including all patients with a clinical diagnosis of iris melanoma managed at the Ocular Oncology Service at Wills Eye Institute over 40 years. Patients were divided into three age categories based on age at presentation: children (≤ 20 years), mid-adults (21-60 years), and older adults (>60 years). The clinical features, treatments, and outcomes were statistically analyzed based on patient age at presentation. The main outcome measures were melanoma features and related metastasis and death.

Results: Of 8,101 eyes with uveal melanoma, there were 317 (4%) with iris melanoma, including 24 (8%) children (≤ 20 years), 187 (59%) mid-adults (21-60 years), and 106 (33%) older adults (>60 years). There was no age-related difference in race, sex, tumor quadrant, thickness, pigmentation, associated corectopia, ectropion uveae, hyphema, or extraocular extension. Significant age-related differences were found with mean tumor basal diameter, tapioca appearance, mean intraocular pressure, secondary glaucoma, tumor seeding in angle, and mean number of clock hours of angle seeding. Multivariate analysis of factors predictive of metastasis included extraocular extension and high intraocular pressure. Factors predictive of death included increased tumor thickness and high intraocular pressure. There was no difference in metastasis or death by age group.

Conclusions: Iris melanoma shows significant clinical differences in children versus adults, with smaller tumor size, less tumor seeding in angle, and lower incidence of secondary glaucoma. There was no significant difference in metastasis or death by age group.
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http://dx.doi.org/10.1016/j.jaapos.2011.10.012DOI Listing
February 2012

Vitreous hemorrhage after plaque radiotherapy for uveal melanoma.

Retina 2012 Jun;32(6):1156-64

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Purpose: The purpose of this article is to determine the incidence, etiology, management, and outcome of vitreous hemorrhage (VH) after plaque radiotherapy for uveal melanoma.

Methods: Retrospective review of medical records.

Results: Of 3,707 eyes treated with plaque radiotherapy for uveal melanoma, VH developed in 4.1% at 1 year, 15.1% at 5 years, and 18.6% at 10 years by Kaplan-Meier analysis. Presumed causes of VH included tumor necrosis (29%), proliferative radiation retinopathy (24%), posterior vitreous detachment (16%), vascular occlusion (5%), and unknown (19%). Tumor necrosis was the most common cause of VH early in the follow-up period (3% at 1 year), while proliferative radiation retinopathy was the most common source of VH later (6.2% at 15 years). The most common initial management was conservative observation for resolution in 48%, laser photocoagulation in 24%, and vitrectomy in 18%. After a mean follow-up period of 5 years, the VH was completely resolved in 41%, partially resolved in 19%, unresolved in 20%, worsened in 5%, and enucleation was necessary in 15%. By multivariable analysis, risk factors for development of VH were the presence of diabetic retinopathy at first visit (relative risk, 6.64), shorter tumor distance to the optic disc (relative risk, 1.07), greater initial tumor thickness (relative risk, 1.1), and break in the Bruch membrane (relative risk, 2.93). The rates of local tumor recurrence, extraocular extension, and distant metastasis in 74 patients who underwent vitrectomy for VH removal after tumor regression were similar to those in patients who did not have vitrectomy for VH.

Conclusion: Vitreous hemorrhage occurs after plaque radiotherapy for uveal melanoma in 15.1% of the patients by 5 years. The main factors predictive of VH included underlying diabetic retinopathy, closer tumor proximity to the disc, greater tumor thickness, and break in the Bruch membrane. After tumor regression, vitrectomy for blood removal appears to be safe.
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http://dx.doi.org/10.1097/IAE.0b013e3182340cc1DOI Listing
June 2012

The impact of ferritin fluctuations on stable hemoglobin levels in hemodialysis patients.

Clin Exp Nephrol 2012 Jun 24;16(3):448-55. Epub 2012 Jan 24.

Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Background: Hemoglobin (Hb) cycling in patients with renal anemia might be associated with a higher mortality rate. We investigated the association of factors relating serum ferritin and dose of erythropoiesis-stimulating agents (ESAs) with Hb levels.

Methods: We measured Hb and ferritin levels every month in 266 hemodialysis (HD) patients for 12 months.

Results: The standard deviation (SD) and residual SD (RSD) (liner regression of Hb or ferritin SD values) values of Hb were significantly correlated with ferritin SD or RSD values, respectively. The percentage achievement of target Hb in the target-ferritin group was significantly higher than in the high-amplitude fluctuation ferritin group. Ferritin SD and RSD values in patients with oral or no iron supplementation were significantly lower than those who received intravenous iron.

Conclusion: Iron storage varies over a relatively wide range in HD patients, and this variation is closely associated with Hb cycling. The stability of iron storage and ESA dosage is important for maintaining stable Hb levels.
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http://dx.doi.org/10.1007/s10157-011-0584-0DOI Listing
June 2012

Effects of acetate-free citrate-containing dialysate on metabolic acidosis, anemia, and malnutrition in hemodialysis patients.

Artif Organs 2012 Mar 29;36(3):282-90. Epub 2011 Sep 29.

Department of Internal Medicine Division of Kidney and Dialysis, Hyogo College of Medicine Seishoukai Aoi Hospital, Nishinomiya, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan.

Previously, dialysate contained small amounts of acetate as an alkaline buffer. Recently, acetate-free dialysate (A[-]D) has been available. We evaluated the clinical effect of A(-)D over acetate-containing dialysate (A(+)D) on acid-base balance, anemia, and nutritional status in maintenance hemodialysis (MHD) patients. Twenty-nine patients on MHD were treated with A(+)D for 4 months (first A(+)D), switched to A(-)D for 4 months, and returned to A(+)D for the next 4-month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3(-) ) levels did not change in patients with normal HCO3(-) levels (≥20 mEq/L) throughout the study. Meanwhile, in patients with initially low HCO3(-) levels, it was significantly increased during the A(-)D period only. Anemia: In patients with target hemoglobin (Hb) ≥10 g/dL, Hb levels were maintained during the study period, even if the dose of erythropoiesis-stimulating agents (ESAs) decreased. In patients with low Hb levels, it was significantly increased in the A(-)D period without increasing ESA or iron doses. Nutritional Condition: In patients with normal albumin levels (≥3.8 g/dL), albumin did not change throughout the study period. However, in patients with lower albumin levels, it was significantly increased during the A(-)D period. These improvements in metabolic acidosis, anemia, and nutrition in the A(-)D period completely dissipated during the second A(+)D period. Hemodialysis (HD) with A(-)D may improve a patient's clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA, and malnutrition that were not normalized in HD with A(+)D.
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http://dx.doi.org/10.1111/j.1525-1594.2011.01349.xDOI Listing
March 2012

One-year choroidal thickness results after photodynamic therapy for central serous chorioretinopathy.

Retina 2011 Oct;31(9):1921-7

Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Purpose: To retrospectively evaluate choroidal thickness 1 year after photodynamic therapy in eyes with central serous chorioretinopathy using optical coherence tomography.

Methods: Central serous chorioretinopathy was diagnosed using fluorescein angiography, and indocyanine green angiography was used to evaluate choroidal vascular hyperpermeability. We measured the subfoveal choroidal thickness using enhanced depth imaging optical coherence tomography.

Results: Thirteen eyes (13 patients; average age, 56.8 years) with central serous chorioretinopathy were observed 1 year after half-dose photodynamic therapy with verteporfin. The mean subfoveal choroidal thickness decreased significantly from 397 ± 108 μm at baseline to 323 ± 120 μm at 1 month, 312 ± 117 μm at 3 months, 317 ± 117 μm at 6 months, and 321 ± 122 μm at 1 year (P < 0.01, for each comparison with baseline). However, the subfoveal choroid thickness significantly increased 2 days after photodynamic therapy to 441 ± 120 (P < 0.01) compared with baseline. Central serous chorioretinopathy did not recur in any patient. Indocyanine green angiography images at 3 months showed less choroidal vascular hyperpermeability compared with baseline.

Conclusion: Half-dose photodynamic therapy for central serous chorioretinopathy resulted in thinner subfoveal choroidal thickness 1 month after treatment, decreased the choroidal vascular hyperpermeability, and maintained the remission for 1 year. Enhanced depth imaging optical coherence tomography was helpful for monitoring the pathophysiologic choroidal changes in central serous chorioretinopathy.
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http://dx.doi.org/10.1097/IAE.0b013e31822bf6b1DOI Listing
October 2011

A crossover study of the acrylonitrile-co-methallyl sulfonate and polysulfone membranes for elderly hemodialysis patients: the effect on hemodynamic, nutritional, and inflammatory conditions.

ASAIO J 2011 Jul-Aug;57(4):293-9

Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Japan.

Many maintenance hemodialysis (MHD) patients have recently been treated with high flux (HF) dialysis membranes such as polysulfone (PSu) membranes. However, the appropriateness of HF for elderly MHD remains to be elucidated. In order to estimate hemodialysis (HD) efficiency, the hemodynamic condition during HD, and the nutritional status, 28 elderly MHD patients were treated with PSu for 3 months. After this, the patients were switched to acrylonitrile-co-methallyl sulfonate (AN69) membranes for the next 3 months and then returned to PSu for another 3 months. Reduction ratio of inflammatory cytokines (interleukin [IL]-6) by AN69 was significantly higher than the reduction ratio by PSu. After 3 months with AN69, the serum total protein, albumin, and cholesterol levels significantly increased, and after switching back to PSu, the levels returned to baseline. Furthermore, the frequency of saline used to treat episodes of hypotension during HD significantly decreased in the AN69 period. In elderly MHD patients, it was possible to achieve improvements in both malnutrition and chronic inflammatory conditions with AN69. This suggests that AN69 may be the preferred membrane for elderly MHD, because it stabilizes the hemodynamic condition and demonstrates a higher removal of inflammatory cytokines during HD.
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http://dx.doi.org/10.1097/MAT.0b013e31821796f1DOI Listing
October 2011

Hepcidin as well as TNF-α are significant predictors of arterial stiffness in patients on maintenance hemodialysis.

Nephrol Dial Transplant 2011 Aug 18;26(8):2663-7. Epub 2011 Jan 18.

Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.

Background: Dysregulated iron metabolism has been suspected to be linked to anemia of chronic disease and to cardiovascular disease (CVD). For the purpose of clarifying the factors affecting arterial stiffness, we evaluated the relationship between iron metabolism, brachial-ankle (ba)-pulse wave velocity (PWV) and several risk factors for CVD in maintenance hemodialysis (MHD) patients.

Methods: A total of 168 MHD patients were recruited, and the levels of iron parameters, hepcidin, CVD risk factors and ba-PWV were evaluated. The level of serum hepcidin-25 was specifically measured by liquid chromatography-tandem mass spectrometry.

Results: Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and hepcidin were higher in MHD patients, which was consistent with results from our previous study. ba-PWV significantly correlated with age (P < 0.01, R = 0.34), total cholesterol (T-CHO; P = 0.02, R = 0.21), TNF-α (P < 0.01, R = 0.24) and hepcidin (P < 0.01, R = 0.25) but not with other iron parameters and CVD risk factors. According to multiple regression analysis, age (β = 0.30), T-CHO (β = 0.24) TNF-α (β = 0.19) and hepcidin (β = 0.23) were selected as the significant predictors of ba-PWV in MHD patients.

Conclusion: Serum levels of both hepcidin and TNF-α are independently associated with arterial stiffness in MHD patients, suggesting that microinflammation and iron metabolism might affect the integrity of arterial walls.
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http://dx.doi.org/10.1093/ndt/gfq760DOI Listing
August 2011

A case of a maintenance hemodialysis patient in whom a change of sensitivity to acetate was suspected.

ASAIO J 2010 Sep-Oct;56(5):488-90

Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Sodium acetate, which is a buffering agent in dialysates, has a vasodilatation effect as well as effects for depression of myocardial contractility even in low dosages. Also, it is presumed to be one of the causes of hypotension during hemodialysis (HD). In recent years, acetate-free dialysates [A(-)D] have been developed. In this case, although it was possible to maintain a relatively stable hemodynamic condition during HD using 10 mEq/L of acetate-containing dialysate [A(+)D], after HD using A(-)D for 4 months and then switched back to A(+)D, the patient complained of several symptoms such as nausea, vomiting, and headache, and severe hypotension episodes increased during HD. Furthermore, stabilization of the hemodynamic condition was obtained after switching back to A(-)D. Moreover, the nutritional state and anemia were improved. Conventionally, it has been considered that cases referred to as acetate intolerance have various symptoms with increasing blood acetate levels; however, this case suggests the possibility that tolerance to acetate was acquired by using the A(+)D over time, and the tolerance dissipated after using the A(-)D for 4 months. The number of cases involving broadly defined acetate intolerance as in this case was higher than expected. These findings suggest that using A(-)D for such cases, it may therefore be possible to maintain stable hemodynamic conditions during HD and improve the nutritional state and anemia.
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http://dx.doi.org/10.1097/MAT.0b013e3181f11e9dDOI Listing
January 2011

Determinants of hepcidin in patients on maintenance hemodialysis: role of inflammation.

Am J Nephrol 2010 14;31(6):534-40. Epub 2010 May 14.

Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Background/aim: Hepcidin could be one of the most important regulators for iron metabolism in patients on maintenance hemodialysis (MHD). The factors affecting serum hepcidin levels were evaluated among indexes of anemia, iron metabolism, or inflammation, as well as the dose of erythropoietin.

Methods: 198 MHD patients treated with recombinant human erythropoietin were recruited and serum hepcidin-25 levels were specifically measured by liquid chromatography tandem mass spectrometry.

Results: In multivariate analysis, only transferrin and ferritin were selected as significant predictors of hepcidin in all patients. In the selected patients with highly sensitive C-reactive protein of >0.3 mg/dl, however, ferritin as well as the IL-6 level were found to be significant predictors for serum hepcidin. The serum ferritin/hepcidin ratio was very similar among MHD and healthy volunteers, suggesting that uremic conditions do not affect the ratio. Serum hepcidin levels decreased by only 27% after a single hemodialysis session, but returned to basal levels 1 h after and remained so until the next hemodialysis session.

Conclusions: In the absence of apparent inflammation, the serum hepcidin level could be exclusively associated with ferritin in MHD patients and was independent of inflammatory cytokines. Only in the presence of microinflammation, however, might IL-6 also affect hepcidin expression.
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http://dx.doi.org/10.1159/000312381DOI Listing
October 2010

The impact of beta2-microglobulin clearance on the risk factors of cardiovascular disease in hemodialysis patients.

ASAIO J 2010 Jul-Aug;56(4):326-32

Division of Nephrology and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

beta2-Microglobulin (beta2M) is an independent predictor of outcome for hemodialysis (HD) patients and a representative substance of middle molecules. We tested the relationship among serum beta2M levels and cardiovascular disease (CVD) risk factors in HD patients. A total of 132 HD patients were divided according to the dialysis membrane used [property; cellulose and synthetic or beta2M clearance; low filtration (LF), middle filtration (MF), and high filtration (HF)]. There was no significant difference in CVD risk factors between cellulose and synthetic groups. On the other hand, serum beta2M, highly-sensitive C-reactive protein (hCRP), troponin-T (TnT), and myeloperoxidase (MPO) levels of LF were significantly higher and those of prealbumin (PA) were lower than the MF and HF. Serum beta2M level was positively correlated with hCRP, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), MPO, TnT, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inversely correlated with PA and ankle-brachial index (ABI). There was a significant correlation between serum beta2M levels and various CVD risk factors in HD. Cardiovascular disease risk factors in HD patients were dependent on the beta2M clearance but not membrane property.
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http://dx.doi.org/10.1097/MAT.0b013e3181de0842DOI Listing
September 2010

Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma.

Ophthalmology 2010 May 15;117(5):1005-12. Epub 2010 Jan 15.

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Purpose: To determine risk factors, occurrence rate, management, and outcome of proliferative radiation retinopathy (PRR) after plaque radiotherapy for uveal melanoma.

Design: Case-control study.

Participants: Three thousand eight hundred forty-one patients who underwent plaque radiotherapy for uveal melanoma were entered into the study.

Methods: Retrospective review of medical records.

Main Outcome Measures: Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma.

Results: Of 3841 eyes treated with plaque radiotherapy for uveal melanoma, PRR developed in 5.8% at 5 years and in 7% at 10 and 15 years using Kaplan-Meier analysis. The mean time to onset of PRR was 32 months (median, 30 months; range, 4-88 months). On univariate analysis, baseline factors predictive of PRR (P<0.05) included young age, diabetes, hypertension, Hispanic race, shorter tumor distance to the optic disc and to the foveola, Bruch's membrane rupture, choroidal location of the tumor, subretinal fluid, higher radiation dose to the optic nerve and to the foveola, higher radiation rate to the tumor apex and to the tumor base, additional transpupillary thermotherapy, and notched plaque. In the multivariate model, young age (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.25-1.67, per decade decrease), diabetes mellitus (OR, 2.73; 95% CI, 1.69-4.40), and shorter tumor distance to the optic disc (OR, 1.10; 95% CI, 1.04-1.17) were related to the occurrence of PRR. The most common forms of management included panretinal photocoagulation (70%), vitrectomy (21%), and observation (17%). Resolution of the neovascularization was obtained in 63% of eyes after treatment.

Conclusions: Proliferative radiation retinopathy developed in 7% of eyes by 10 years after plaque radiotherapy for uveal melanoma. The main factors for development of PRR included young age, preexistent diabetes mellitus, and shorter tumor distance to the optic disc.
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http://dx.doi.org/10.1016/j.ophtha.2009.10.015DOI Listing
May 2010

Retinal arteriolar macroaneurysm and congenital retinal macrovessel.

Ophthalmic Surg Lasers Imaging 2009 Sep-Oct;40(5):513-5

Vitreous-Retina-Macula Consultants of New York, and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, NY 10022, USA.

Variations in the morphology of the aneurysm and its serosanguineous complications serve to make a retinal arteriolar macroaneurysm, a common masquerading entity, particularly if it is accompanied by another un-associated retinal vascular abnormality. The authors present a patient who had an unusually large retinal arteriolar macroaneurysm in conjunction with a congenital retinal macrovessel.
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http://dx.doi.org/10.3928/15428877-20090901-15DOI Listing
November 2009

Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes.

Arch Ophthalmol 2009 Aug;127(8):989-98

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, 840 Walnut St, Ste 1440, Philadelphia, PA 19107, USA.

Objective: To determine the rate of metastasis of uveal melanoma on the basis of tumor thickness in millimeters.

Methods: Retrospective medical record review.

Results: The mean (median) patient age was 58 (59) years. A total of 8033 eyes were examined. Of the 285 eyes with iris melanoma, the mean tumor thickness was 2.7 mm and metastasis occurred in 0.5%, 4%, and 7% at 3, 5, and 10 years, respectively. Of the 492 eyes with ciliary body melanoma, the mean tumor thickness was 6.6 mm and metastasis occurred in 12%, 19%, and 33% at 3, 5, and 10 years, respectively. Of the 7256 eyes with choroidal melanoma, the mean tumor thickness was 5.5 mm and metastasis occurred in 8%, 15%, and 25% at 3, 5, and 10 years, respectively. For all uveal melanoma, metastasis at 5, 10, and 20 years was 6%, 12%, and 20% for small melanoma (0-3.0 mm thickness), 14%, 26%, and 37% for medium melanoma (3.1-8.0 mm), and 35%, 49%, and 67% for large melanoma (>8.0 mm). More specifically, metastasis per millimeter increment at 10 years was 6% (0-1.0 mm thickness), 12% (1.1-2.0 mm), 12% (2.1-3.0 mm), 16% (3.1-4.0 mm), 27% (4.1-5.0 mm), 28% (5.1-6.0 mm), 29% (6.1-7.0 mm), 41% (7.1-8.0 mm), 50% (8.1-9.0 mm), 44% (9.1-10.0 mm), and 51% (>10.0 mm). Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, having a brown tumor, and the presence of subretinal fluid, intraocular hemorrhage, or extraocular extension.

Conclusion: Increasing millimeter thickness of uveal melanoma is associated with increasing risk for metastasis.
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http://dx.doi.org/10.1001/archophthalmol.2009.208DOI Listing
August 2009

Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases.

Arch Ophthalmol 2009 Aug;127(8):981-7

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Objective: To determine features that are predictive of growth of choroidal nevi into melanoma.

Methods: This was a retrospective medical record review of 2514 consecutive eyes; Kaplan-Meier estimates and Cox regression analyses were used.

Results: The median tumor basal diameter was 5.0 mm and thickness was 1.5 mm. Nevus growth into melanoma occurred in 2%, 9%, and 13% of eyes at 1, 5, and 10 years, respectively. Factors predictive of growth into melanoma by multivariable analysis included tumor thickness greater than 2 mm (P < .001), subretinal fluid (P = .002), symptoms (P = .002), orange pigment (P < .001), tumor margin within 3 mm of the optic disc (P = .001), ultrasonographic hollowness (P < .001), and halo absence (P = .009). A mnemonic device to recall risk factors of ocular melanoma is "To find small ocular melanoma using helpful hints," representing thickness, fluid, symptoms, orange pigment, margin, ultrasonographic hollowness, and halo absence. The median hazard ratio for those with 1 to 2 risk factors was 3; for 3 or 4 factors, 5; for 5 to 6 factors, 9; and for all 7 factors, 21.

Conclusions: In an analysis of 2514 choroidal nevi, factors predictive of growth into melanoma included greater thickness, subretinal fluid, symptoms, orange pigment, margin near disc, and 2 new features: ultrasonographic hollowness and absence of halo.
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http://dx.doi.org/10.1001/archophthalmol.2009.151DOI Listing
August 2009
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