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Lotan Y.,University of Texas Southwestern Medical Center | Svatek R.S.,University of Texas Health Science Center at San Antonio | Krabbe L.-M.,University of Texas Southwestern Medical Center | Krabbe L.-M.,University of Muenster Medical Center | And 5 more authors.
Journal of Urology | Year: 2014

Purpose: Few studies have combined clinical prognostic factors with urinary biomarkers into risk profiles that can be used to predict the likelihood of bladder cancer. We previously developed and internally validated a bladder cancer detection nomogram that combines clinical features with the NMP22®BladderChek®test. To consider extensive use of the model the nomogram was tested in a prospective cohort of patients who presented with hematuria.Materials and Methods: Patients referred for hematuria evaluation were prospectively enrolled at 3 centers. Each patient underwent complete urological evaluation, including history, examination, cystoscopy, cytology and NMP22. A logistic regression model to predict urothelial bladder carcinoma was also developed to compare the performance of clinical data with and without adding NMP22 and urinary cytology.Results: The study included 381 patients (50.7% women) with a median age of 58 years. Urothelial bladder carcinoma was detected in 23 patients (6%). It was associated with age greater than 65 (11.1% vs 4% of patients, p =0.012), male gender (10.1% vs 2%, p =0.003), white ethnicity (9.2% vs 3.1%, p =0.016), gross hematuria (9.9% vs 2.5%, p =0.005), positive NMP22 (37% vs 3.7%, p <0.001) and positive cytology (83.3% vs 3.9%, p <0.001). Predictive accuracy of the bladder cancer detection nomogram was 80.2%. The calibration plot indicated that the previously published nomogram was well calibrated in patients with a less than 15% predicted probability of urothelial bladder carcinoma.Conclusions: We prospectively validated a highly accurate tool that combines clinical factors and a urinary biomarker to detect bladder cancer. This tool can help prioritize urological referrals for patients with hematuria. © 2014 American Urological Association Education and Research, Inc.


Krabbe L.-M.,University of Texas Southwestern Medical Center | Krabbe L.-M.,University of Muenster Medical Center | Svatek R.S.,University of Texas Health Science Center at San Antonio | Shariat S.F.,University of Texas Southwestern Medical Center | And 3 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2015

Bladder cancer (BC) screening is not accepted in part owing to low overall incidence. We used the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Cancer Screening Trial (NLST) to identify optimal high-risk populations most likely to benefit from screening. Materials and methods: Data were extracted from PLCO and NLST to stratify risk of BC by overall population, sex, race, age at inclusion, and smoking status. Incidence rates between groups were compared using chi-square test. Results: BC was identified in 1,430/154,898 patients in PLCO and 439/53,173 patients in NLST. BCs were grade III/IV in 36.8% and 41.3%. Incidence rates were significantly higher in men than in women (PLCO: 1.4 vs. 0.31/1,000 person-years and NLST: 1.84 vs. 0.6/1,000 person-years, both P<0.0001). In proportional hazards models, male sex, higher age, and duration and intensity of smoking were associated with higher risk of BC (all P<0.0001). In men older than 70 years with smoking exposure of 30 pack-years (PY) and more, incidence rates were as high as 11.92 (PLCO) and 5.23 (NLST) (per 1,000 person-years). In current high-intensity smokers (≥50 PY), the sex disparity in incidence persists in both trials (0.78 vs. 2.99 per 1,000 person-years in PLCO and 1.12 vs. 2.65 per 1,000 person-years in NLST). Conclusions: Men older than 60 years with a smoking history of>30 PY had incidence rates of more than 2/1,000 person-years, which could serve as an excellent population for screening trials. Sex differences in the incidence of BC cannot be readily explained by the differences in exposure to tobacco, as sex disparity persisted regardless of smoking intensity. © 2014 Elsevier Inc.


Alnawaiseh M.,University of Muenster Medical Center
Cornea | Year: 2015

PURPOSE:: The aim of this study was to determine the efficacy of accelerated riboflavin–ultraviolet A–induced corneal collagen cross-linking (CXL) (irradiance of 18 mW/cm for 5 minutes). METHODS:: In this study, we retrospectively reviewed the charts and anterior segment data of patients after accelerated CXL. Visual, topographic, pachymetry, and densitometry data were extracted and analyzed before surgery and at follow-up (minimum 12 months) after treatment. RESULTS:: A total of 28 eyes of 20 patients (mean age, 28.1 ± 8.1 years) were included in this study. The mean follow-up time was 21.7 ± 7.2 months (range, 12–34 months). No statistically significant changes were found in the mean corrected distance visual acuity, corneal astigmatism, Kmean, Kflat, Ksteep, corneal pachymetry (at the apex and at the thinnest point), and corneal densitometry at follow-up. A significant reduction of Kmax, index of surface variance, index of vertical asymmetry, and Km of the posterior corneal surface (Km) was observed (Kmax: P = 0.018; index of surface variance: P = 0.016; index of vertical asymmetry: P = 0.038; Km: P = 0.008). No complications were reported during the postoperative follow-up period in this study. CONCLUSIONS:: Based on a mean follow-up time of 21.7 months, accelerated CXL (18 mW/cm; 5 minutes) is effective in stopping the progression of keratoconus without raising any safety concerns. Improvement in Kmax and stabilization of corrected distance visual acuity were noted after treatment. However, prospective studies with longer follow-up using different accelerated CXL settings are needed to validate these findings. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Alten F.,University of Muenster Medical Center | Clemens C.R.,University of Muenster Medical Center | Heiduschka P.,University of Muenster Medical Center | Eter N.,University of Muenster Medical Center
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2014

Background: To analyse reticular pseudodrusen (RPD) in patients with age-related macular degeneration (AMD) using multi-spectral (MS), confocal scanning laser ophthalmoscopy (cSLO). Methods: cSLO images (blue fundus autofluorescence [FAF; exc., λ=488; em., λ=500-700 nm], near-infrared reflectance [IR; λ=820 nm], MS [blue reflectance (BR) λ=488 nm, green reflectance (GR) λ=515 nm, IR λ=820 nm], as well as colour fundus photographs (CFP) were taken of 200 eyes from 100 AMD patients suspected to show RPD on the basis of funduscopy or previous fundus imaging. FAF and IR images were graded by two independent readers. If both readers concordantly confirmed the presence of RPD in both modalities, eyes were subsequently also graded for RPD in MS, BR, GR, green-blue enhanced mode (GBE), and CFP. Besides, FAF, IR, and MS images were evaluated for the presence of a target aspect, which represents a common feature of RPD lesions. Results: The presence of RPD was confirmed using FAF and IR images by both readers in 130 eyes of 76 patients. In those eyes, both readers concordantly diagnosed RPD in MS images in 124 (95.4 %) eyes (BR: 52 [40.0 %], GR: 63 [48.5 %], GBE: 101 [77.7 %], CF: 27 [20.8 %]). Cohen kappa statistics revealed excellent inter-observer agreement for MS (0.95) and GBE (0.85), substantial agreement for BR (0.75), GR (0.78), and moderate agreement for CFP (0.59). A target aspect within RPD lesions was detected in 45 of 130 (35.0 %) included eyes using FAF and IR. The presence of a target aspect improved the recognition of RPD lesions in all modalities. If a target aspect was present, RPD were diagnosed in 45 eyes (100 %) using MS (GBE: 42 eyes [93.3 %], BR: 30 eyes [66.7 %], GR: 37 eyes [82.2 %], CFP: 17 eyes [37.8 %]). Using MS cSLO, a target aspect could be identified in 75 of 130 (57.7 %) included eyes. Conclusions: MS cSLO imaging is equivalent to FAF and IR in identifying RPD in AMD patients. Higher identification rates in BR and GR of those RPD lesions featuring a target aspect confirm the current hypothesis of RPD localisation and its progression further into the photoreceptor layers. MS seems to be more sensitive in identifying a central target aspect in RPD lesions compared to blue FAF and IR. © 2013 Springer-Verlag.


Alten F.,University of Muenster Medical Center | Heiduschka P.,University of Muenster Medical Center | Clemens C.R.,University of Muenster Medical Center | Eter N.,University of Muenster Medical Center
Investigative Ophthalmology and Visual Science | Year: 2014

PURPOSE. To describe longitudinal structure/function correlations in eyes with progressive reticular pseudodrusen (RPD).METHODS. Thirteen eyes of 12 patients with exclusively RPD in the posterior pole were included (75.1 ± 5.7 years). All patients underwent spectral-domain optical coherence tomography (SD-OCT), confocal scanning laser ophthalmoscopy (cSLO), and multifocal electroretinography (mfERG) at baseline and 12-month follow-up. Size of retinal area affected by RPD, number and stages of RPD lesions, and choroidal thickness (CT) were quantified at baseline and at follow-up visit. Amplitudes obtained by mfERG in RPD eyes at baseline and follow-up were analyzed and correlated to morphologic changes. Eyes were compared to those of age-matched healthy controls.RESULTS. The total number of RPD lesions increased from 540 at baseline to 667 at 12-month follow-up. Mean CT was 198.5 ± 69.3 lm at baseline (control group 263.5 6 42.6 lm; P ¼ 0.005) and 189.2 ± 65.3 lm at follow-up (P < 0.001) (control group 265 ± 47.8 lm; P ¼ 0.74). A mean growth of RPD-affected area of 3.3 mm2 was measured. Multifocal ERG amplitudes decreased in both the study and control groups to a similar extent. Amplitudes differed significantly at the follow-up time point when compared between RPD-affected and nonaffected areas within the same eye. No correlations between changes of morphologic parameters and mfERG amplitude changes were found.CONCLUSIONS. Multifocal ERG allows for detecting a decline of function over time in eyes with progressive RPD. Yet functional decline could not be correlated to changes in individual morphologic parameters. © 2014 The Association for Research in Vision and Ophthalmology, Inc.


Alnawaiseh M.,University of Muenster Medical Center | Rosentreter A.,University of Muenster Medical Center | Eveslage M.,University of Munster | Eter N.,University of Muenster Medical Center | Zumhagen L.,University of Muenster Medical Center
Journal of Refractive Surgery | Year: 2015

PURPOSE: To determine long-term changes in corneal transparency after riboflavin-ultraviolet A-induced corneal collagen cross-linking (CXL). METHODS: Charts and anterior segment data of patients after CXL for progressive keratoconus were retrospectively reviewed. Patients were examined using the Scheimpflug-based Pentacam corneal densitometry module (Oculus Optikgeräte, Wetzlar, Germany) before CXL and at five postoperative follow-up visits: 1 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 36 months. RESULTS: Forty-two eyes of 28 patients (mean age: 27.9 ± 8.6 years) were included. Total corneal light backscatter was higher 1 to 3 months after CXL than before CXL (P < .001). There were significant differences, especially in the anterior (P < .001) and central (P < .001) layer at total diameter and posterior layer (P = .014) and the three central annuli at total corneal thickness (0 to 2 mm: P < .001; 2 to 6 mm: P < .001; 6 to 10 mm: P = .002). Total corneal light backscatter at total corneal thickness and total diameter faded over time following CXL. The backscatter was significantly lower 24 to 36 months after CXL than before CXL (P < .001). CONCLUSIONS: Corneal densitometry peaks in the first months after CXL and returns to preoperative values approximately 1 year after CXL. Two years after CXL, corneal densitometry reaches values obtained for healthy, untreated corneas, thus achieving an improvement in corneal clarity over untreated keratoconic corneas. Copyright © SLACK Incorporated.


Clemens C.R.,University of Muenster Medical Center
Retina | Year: 2015

PURPOSE:: To evaluate a morphology score for drusenoid pigment epithelial detachment (dPED) regarding predictability of a decline in retinal function beyond best-corrected visual acuity.METHODS:: Thirteen eyes of 10 patients with dPED due to age-related macular degeneration (AMD) were included (age 72.8 ± 4.2 years). All underwent volume spectral domain optical coherence tomography, fluorescence angiography, and confocal scanning laser ophthalmoscopy infrared imaging as well as multifocal electroretinography and microperimetry. The dPED morphology score suggested consists of five parameters: hyperreflective spots in infrared, lesion diameter, lesion height, presence of vitelliform-like material in the subretinal space or subretinal fluid, and integrity of the ellipsoid zone in spectral domain optical coherence tomography. Subsequently, a score value between 0 and 1 according to the extent of morphologic changes was correlated to foveal multifocal electroretinography and microperimetry measurements.RESULTS:: The mean best-corrected visual acuity was 20/40. The mean height and mean diameter of dPED were 312.2 ± 111 μm and 2,535 ± 805 μm. Two dPED showed no hyperreflective spots in confocal scanning laser ophthalmoscopy infrared images, three displayed a moderate stage of hyperreflective spots, and eight had severe hyperreflective spots. Two eyes showed subretinal fluid, and five patients showed vitelliform-like material in the subretinal space. Eight eyes revealed a severe disruption of the ellipsoid zone. Although no correlation was found between dPED morphology score and best-corrected visual acuity, eyes with a dPED morphology score >0.5 revealed distinctly decreased values in functional measurements compared with those with a score ≤0.5.CONCLUSION:: The dPED morphology score aggregates all currently known morphologic changes in dPED and represents a valuable tool for clinical lesion evaluation. Furthermore, it allows for assessing an estimate of functional decline beyond best-corrected visual acuity. © 2015 by Ophthalmic Communications Society, Inc.


Alten F.,University of Muenster Medical Center | Eter N.,University of Muenster Medical Center
British Journal of Ophthalmology | Year: 2015

Drusen are focal deposits of extracellular material located between the retinal pigment epithelium (RPE) and Bruch's membrane and represent the major phenotypic characteristic of age-related macular degeneration (AMD). Due to evolving imaging techniques and recent histological studies, reticular pseudodrusen (RPD) have received increasing attention and have been recently identified as an additional phenotypic entity in AMD. In contrast to conventional drusen, RPD proved to be located internal to the RPE. In the past few years, numerous studies collected new findings on RPD related to their pathogenesis, imaging properties and impact on retinal function. While most former natural history studies as well as interventional studies in early AMD did not include imaging RPD beyond colour fundus photography, this phenotype must be included in every future large-scale study on AMD. This review summarises the current knowledge on RPD.


Clemens C.R.,University of Muenster Medical Center | Alten F.,University of Muenster Medical Center | Baumgart C.,University of Muenster Medical Center | Heiduschka P.,University of Muenster Medical Center | Eter N.,University of Muenster Medical Center
Retina | Year: 2014

Purpose: To compare different quantification tools based on confocal scanning laser ophthalmoscopy for assessment of retinal pigment epithelium (RPE) tear area size. Methods: Confocal scanning laser ophthalmoscopy fundus autofluorescence (FAF) and near-infrared reflectance (IR) images were retrospectively evaluated in 23 patients with RPE tear after intravitreal injection for pigment epithelium detachment due to exudative age-related macular degeneration at baseline and additionally in 11 patients after 5.1 ± 1.8 months of follow-up. Retinal pigment epithelium tear area was measured by three independent readers using three methods: manually on confocal scanning laser ophthalmoscopy FAF images, manually on confocal scanning laser ophthalmoscopy IR images, and using an FAF-based semiautomated software. Results: Confidence intervals were 0.08 and 0.12 for FAF, 0.11 and 0.09 for FAF-based semiautomated software, and 0.25 and 0.27 for IR for intraobserver (Reader 1) and interobserver agreements (Readers 1 and 2), respectively. The average values of the square errors of the quantification methods were 0.040 ± 0.033 mm2 (FAF), 0.035 ± 0.060 mm2 (software), and 0.187 ± 0.219 mm2 (IR). Mean area of RPE tears at baseline given as the average measurement of all 3 readers using FAF-based semiautomated software was 5.77 ± 4.62 mm2 (range, 0.13-14.74 mm2). Follow-up measurements of unilobular RPE tears (8 patients) showed no change in lesion area size (0.14 ± 0.33 mm2); in contrast, multilobular RPE tears (3 patients) showed a progression in lesion area size of 1.80 ± 0.74 mm2. Conclusion: Manual FAF-based and semiautomated FAF-based quantifications of RPE tear area are accurate and reproducible and superior to manual IR-based measurement. Retinal pigment epithelium tear area quantification is clinically relevant regarding further intravitreal treatment, particularly in multilobular RPE tears. Copyright © 2014 by Ophthalmic Communications Society, Inc.


Alten F.,University of Muenster Medical Center | Clemens C.R.,University of Muenster Medical Center | Heiduschka P.,University of Muenster Medical Center | Eter N.,University of Muenster Medical Center
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. We identified a topographic relation of localized reticular pseudodrusen (RPD) to choroidal watershed zones (CWZ) and to changes in choroidal volumes (CV). METHODS. We included 30 eyes of 30 patients with RPD in an area <10 mm2 and no other retinal alteration (76.7 ± 6.9 years). Patients underwent spectral-domain optical coherence tomography (SD-OCT), enhanced depth imaging (EDI) OCT, fluorescein video-angiography (vFA), indocyanine green video-angiography (vICG), and confocal scanning laser ophthalmoscopy (cSLO). vICG was evaluated for the presence, localization, and configuration of CWZ. Retinal areas affected by RPD were measured, and their localization was determined in relation to CWZ. CV was measured using a choroidal thickness map of the posterior pole and the Early Treatment of Diabetic Retinoscopy Study (ETDRS) grid. RESULTS. In all study eyes, RPD could be demonstrated clearly in SD-OCT, EDI-OCT, FA, ICG, and cSLO. CWZ were identified in 25 eyes (83.3%). The area affected by RPD was 7.45 ± 2.25 mm2. RPD area was located fully or partly within the CWZ in 22 eyes (88.0%). Mean CV in the full ETDRS grid area was reduced significantly (4.49 ± 1.44 mm3). Foveal CV and CV in the grid sector affected mostly by RPD were significantly diminished to 0.14 ± 0.05 mm3 and 0.85 ± 0.38 mm3, respectively. CONCLUSIONS. The site of localized RPD seems to be related to presence and site of CWZ, suggesting that choroidal hypoxia may have a role in RPD pathogenesis. Reduced CV in eyes with localized RPD could be demonstrated and may be cause or consequence of RPD development. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

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