bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active caspase‐3 expression in healthy lens epithelium
Authors: TALEBI ZADEH N , YU Z , KRONSCHLÄGER M , SÖDERBERG P 
Published: November 2013

AbstractPurpose To determine the distribution and localization of active caspase‐3 in normal rat lens epithelium by immunohistochemistry.Methods Alltogether, 40 Sprague Dawley rats were sacrificed and eye lenses were removed. One eye from each animal was fixed and then stored at ‐80°C. Three mid‐sagittal sections of each lens were processed for immunohistochemistry. Lens epithelial cell position was identified and specified as its consecutive position in relation to the first nucleus counted. The counting started from one nuclear bow and ended in the opposite side nuclear bow. The nuclei labelled with active caspase‐3 and their relative position was identified three times, counts, in each section. Then, each lens was divided into fifteen segments and active caspase‐3 labelling was calculated in each segment.Results Active caspase‐3 was more expressed in the anterior pole of the lens with the of 37 % active caspase‐3 labelled cells. The variance for animals, sections and countings was estimated to 11, 3 and 83 %, respectively. Fitting the fraction of labelling to a double exponential model, as a function of segment number starting from the anterior pole, assuming an exponential decrease from the anterior pole toward periphery, resulted in a 95 % confidence interval for decrease rate (1/k) = ‐1.5±0.2 segments and inflection point = 7.7±0.2 segmentsConclusion Active caspase‐3 is present in the normal lens, with a maximum activity around the anterior pole that tapers off towards the periphery. Quantitative analysis of immunoflorescence of active caspase‐3 requires at least 3 sections per lens. The number of countings of labelled nuclei is the limiting factor for the precision in an estimate of fraction of labelling.
Elastic properties of human lens zonules as a function of age in presbyopes
Authors: MIKIELEWICZ M , MICHAEL R , MONTENEGRO G , PINILLA CORTES L , BARRAQUER RI 
Published: November 2013

AbstractPurpose Ex vivo measurement of the elastic properties of human lens zonules as a function of age in presbyopes.Methods We studied 16 presbyopic human donor eyes (ages 47 to 97). Anterior eye sections with crystalline lens, zonules, ciliary body and sclera were radially stretched. The stretching device consists of a chamber filled with balanced salt solution and eight radial hooks to hold the anterior eye section. Radial stretching was created with a stepper motor connected to a digital outside micrometer for linear displacement and digital balance for force measurement. Three eye globes were used to test our methodology. For 13 eye globes, the spring constant, elastic modulus of the zonular system, and Young's modulus of the zonules were calculated.Results We found linear dependence for force‐elongation and force‐strain relationships at all ages. In young presbyopic eyes (ages 47 to 60), the Young's modulus of the zonules was 340 mN/mm²; whereas in older eyes (ages 83 to 97), it was significantly lower at 270 mN/mm². However, the correlation coefficient between Young's modulus and age (47 to 97 years) was not significant with p = 0.063.Conclusion The zonular system in presbyopic eyes is linear elastic, and the Young's modulus of the zonules decreases 20% from presbyopic age to late presbyopic age. However, there was no significant correlation between Young's modulus and age in presbyopes.
Different assessments of immunohistochemically stained Ki‐67 ocular malignancies
Authors: PAULAVICIENE R , PETROSKA D , ASOKLIS R 
Published: November 2013

AbstractPurpose To investigate a tumor proliferation marker Ki‐67 in conjunctival malignancies and to compare the results of different quantitative assessments.Methods This study was designed as a pilot study to assess nuclear proliferation protein (Ki 67) in conjunctival malignancies. Immunohistochemical staining of Ki‐67 was evaluated in 8 surgical samples of ocular surface neoplasias: 6 cases of invasive conjunctival squamous carcinoma and 2 of conjuntival melanoma. Ki‐67 counting and evaluation was assessed on selected areas using different methods: manual counting (MC) of >1500 cells;digital image analysis with Nuclear V9 algorithm and digital image analysis using stereology module for ImageScope of Aperio. Ki‐67 values from manual, stereoscopic and automated analyses were compared.Results The MC, the nuclear V9 algorithm analysis and stereologic method revealed positivity of Ki‐67 in invasive conjunctival squamous carcinoma from 22 to 60%, 21.5 to 43.5 % and from 30.1 to 51.5% respectively; in conjunctival melanomas from 20 to 30 %; from 17.8 to 18%, and from 7.17 to 29.1% respectively. The strongest correlation was observed between Aperio algorithm and stereologic method in conjunctival squamous carcinoma (0.87). Weaker correlation was found between Aperio/manual (0.6) and manual/stereological (0.83) methods.Conclusion Our data demonstrate that different methods of Ki‐67 evaluation may give dissimilar results, but results of this computer assisted nuclear V9 algorithm correlates strongly with stereoscopic analysis and can be helpful in accurate quantitative evaluation of imunochistochemically stained biomarkers.
Rare iridociliary pediatric tumors and pseudotumors: Cases report and literature review
Authors: HADJISTILIANOU T , TSYGANKOV A , DE LUCA MC , DEFRANCESCO SONIA , MICHELI L , BORRI M , MENICACCI F 
Published: November 2013

AbstractPurpose Iridociliary tumors are usually uncommon in childhood. Our aim is to describe cases of juvenile xanthogranuloma, iris tuberculoma and medulloepithelioma in young patients and to differentiate them from other similar lesionsMethods Retrospective cases study. Four patients ( two girls and two boys) were referred at the Referral Center for Retinoblastoma of the University of Siena. They underwent all the ophthalmological examination including standard procedures, MRI of the orbits, CT, UBM, immunological and molecular analysis. In three cases organ‐preserving operations were performed.Results Two tumors were histologically identified as medulloepitheliomae. Two tumor‐like lesions were determined as juvenile xanthogranuloma and iris tuberculous granuloma. In the last case, antituberculous therapy was performedConclusion Iridociliary tumors and pseudotumors are rather rare in childhood. Nevertheless, they should be taken in consideration in differential diagnosis with other pediatric intraocular tumors, particularly retinoblastoma, ciliary body adenoma and adenocarcinoma. An executive checkup including pathology, immunohistochemistry and immunology is to be performed.
Expression of stem cell markers in human uveal melanoma
Authors: STEIBER Z , HALMOS G , CSERHATI Z , TRESZL A 
Published: November 2013

AbstractPurpose Uveal melanoma is a rare but very aggressive malignancy. Independently of the currently available therapies, 50 % of uveal melanoma patients will develop metastasis and the average survival time of these patients is only 2‐8 months. Genetic and epigenetic background of uveal melanoma is not fully understood and useful prognostic markers for metastasis development are not well characterized. It was suggested that in various tumors cancer stem cells are responsible for the development of primary tumors and their metastases. In uveal melanoma, the role of cancer stem cells is not clear that’s why our aim with the present study was to investigate the expression of mRNA of stem cell markers.Methods Human uveal melanoma specimens were obtained from 31 enucleated patients at the University of Debrecen, Department of Ophthalmology. The expression of stem cell markers was studied by RT‐PCR, using gene specific primers for FZD6, NES, NGFR, PROM1 and SOX10.Results mRNA for FZD6 and SOX10 could be detected in 100% of the investigated samples. NES, NGFR and PROM1 were present in 94%, 94% and 82%, respectively.Conclusion Results of our study demonstrate that certain stem cell markers are present in nearly all uveal melanoma specimens. Therefore, they are not suitable as prognostic markers. However, our findings that a high percentage of uveal melanomas express stem cell markers support the view that stem cell genes may play an important role in the development and progression of this aggressive cancer. Further studies are needed to evaluate the exact role of these markers and to explore potential therapeutic approaches to target cancer stem cells in human uveal melanoma. Grant support: TÁMOP 4.2.2.A‐11/1/KONV‐2012‐0025 (G.H.)
Trans‐scleral local resection of toxic choroidal melanoma after proton beam radiotherapy
Authors: KONSTANTINIDIS L , DAMATO B 
Published: November 2013

AbstractPurpose To report on trans‐scleral local resection of choroidal melanoma as treatment for serous retinal detachment after proton beam radiotherapy (PBR)Methods Retrospective study of patients underwent trans‐scleral local resection of choroidal melanoma after previous PBR from 2000 to 2008 to the Liverpool Ocular Oncology Service.Results The 11 patients (5 female, 6 male) had a median age of 48.8 years (range 20 – 76) included in this study. The tumor margins extended anterior to ora serrata in 6 patients. On echography, the largest basal tumor dimension averaged 11.9 mm (range 5.7 – 13.2) and the tumor height averaged 7 mm (range 4.5 – 9.9). The retinal detachment was total in 4 cases. Neovascular glaucoma was present in 4 patients. The time between proton beam radiotherapy and local resection had a mean of 17.4 months (range 1 – 84). The follow‐up time after the local resection procedure had a mean of 96 months (range 60 – 156). At the last known status, the eye was conserved in 9 patients, with a flat retina in all of these patients and visual acuity better than 6/30 in 5 patients. The reasons for enucleation were: retinal detachment (1 patient) and phthisis (1 patient.Conclusion Serous retinal detachment and neovascular glaucoma after proton beam radiotherapy of a choroidal melanoma can both resolve after trans‐scleral local resection of the tumor. Our findings indicate that these complications are caused by the persistence of the irradiated tumor within the eye (‘toxic tumor syndrome’).
Case of primary neuroendocrine carcinoma in lacrimal gland
Authors: DAISUKE Y , TOSHIYUKI O , SHUICHI Y 
Published: November 2013

AbstractPurpose Case of primary neuroendocrine carcinoma in lacrimal glandMethods A 86‐year‐old man noticed a swelling of the left upper eyelid three month earlier. Because the size of the nodule gradually increased, the patient was referred to the Chiba University Hospital. We performed excision biopsy and histopathological examination indicated that the tissue had low‐grade atypical cells which were positive to CD56, CK7, and CKAE1/AE3. Magnetic resonance imaging and positron emission tomography excluded systemic metastasis. The patient was diagnosed with a primary NEC of the left lacrimal gland.Results He underwent chemotherapy (Carboplatin and etoposide) for four cycles, and the size of the tumor was significantly decreased. A month later, we performed tumor excision including the clinically visible margin, and a month later the patient had 50Gy radiotherapy at the surgical region. After the three‐combination therapy, the tumor was undetectable in the MRI. A month later, however, a metastasis to the parotid lymph node was found, and the patient underwent total lymphadenectomy of the left parotid gland and 46Gy radiotherapy was applied to the left neck. At the last examination, the patient had neither recurrence nor metastasis.Conclusion Although primary NEC of the lacrimal gland is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined surgery, radiotherapy, and chemotherapy are needed for the complete management of NEC.
Mucormycosis is a rare etiology of ophthalmoplegia: How to diagnose and to manage it, about one exceptional case
Authors: LAGENAITE C 
Published: November 2013

AbstractPurpose Mucormycosis is a rare opportunist infection,characterized by a high mortality rate occurring in immunodeficient patient population.Its rhino‐cerebral form may be complicated by neuro‐ophthalmological and orbital symptomatology.Methods We report a case of a 57 years old woman, referring because of diplopia associated with a diabetic ketoacidosis .Ocular examination revealed a complete left ophthalmoplegia. Magnetic resonance imaging highlighted a cavernous sinus thrombosis associated with ipsilateral pansinusitis. In this context, mucormycosis diagnosis is discussed and confirmed by anatomopathology analysis after sinusal biopsy.The follow‐up is exceptional in its ophthalmological complications despite antifungal agents and anticoagulant therapy.We observed consecutively a left central retinal artery occlusion (CRAO) then a contralateral central retinal veinous occlusion,and finally a left neovascular glaucoma.Results Mucormycosis is a fungal opportunist infection that must be very early diagnosed.This pathology is caracterized by sinusal infiltration, necrosis, and bony walls damage. Medical treatment by anti‐fungal agents alone, can not contain it. It must be associated with a wide and repeated surgical debridement of necrotic tissue. Symptomatic ocular treatment (anti‐VEGF, Laser) is needed in order to preserve visual function and anatomical prognosis.Indeed, the extension along blood vessels walls leads to thrombosis and necrosis, that is resistant to systemic therapy. Our patient is still alive after a follow‐up of 24 months.Conclusion This case illustrates a serious multidisciplinary pathology,that is very difficult to control.The ocular signs were predominant but revealed a large rhino‐cerebral infiltration.
A time‐line model of developmental events within the human fovea based on imaging and histology data
Authors: SJÖSTRAND J , POPOVIC Z 
Published: November 2013

AbstractPurpose To create a time‐line model of developmental events during normal maturation of the inner and outer foveal layers based on imaging and histological studies.Methods Data from recently published imaging studies using hand‐held OCT during the period following premature birth (Dubis et al. 2012; Maldonado et al., 2012; Vajkovic et al., 2012) and histology of normal donor eyes (Dubis et al., 2012; Hendrickson et al. 2012; Vajkovic et al., 2012) was used to establish the timing of foveal developmental events from the time of mid‐gestation to early childhood. A model of the onset and maturation of the following foveal developmental events was constructed: Pit formation, extrusion of inner retinal layers, widening of the outer nuclear layer, separation of the hyperreflective inner segment layer from the RPE, and lengthening of the outer segment. Developmental events were graded as incipient, intermediate or mature.Results The normal developmental events within the central fovea are depicted along a logarithmic time‐line. The developmental models based on OCT or histology of the inner and outer retina show a close correspondence. The structural elements of the inner retina all reach near full to full maturity at term birth. At this time the outer retinal structures are immature and the maturation of the photoreceptor layers starts at an age of some postnatal weeks and reach near full to full maturity at one to three years of age.Conclusion The inner and outer foveal layers reach maturity within different time frames; the inner layers during the late part of gestation, and the outer layers during the first postnatal years. Our model is of importance when evaluating abnormalities in e.g. prematurity or albinism.
Hypoxia stimulates the release of Brain Natriuretic Peptide (BNP) from RPE cells
Authors: ARJAMAA O , KINNUNEN K , KAARNIRANTA K , AALTONEN V 
Published: November 2013

AbstractPurpose The natriuretic peptide system (A‐, B‐ and C‐type) has a powerful effect on systemic blood circulation (natriuresis, diuresis ans plasma shift) causing haemoconcentration causing increased oxygen carrying capapcity of blood. A high concentration of a member of the natriuretic peptide family has been found from the vitreous of patients suffering of proliferative diabetic retinopathy (PDR). The stimulus to which the natriuretic peptide system responded in PDR, however, has remained unknown. We tested the hypothesis that hypoxic conditions will increase the release of BNP (B‐type of natriuretic peptides) from human retinal pigment epithelium (RPE) cell cultureMethods Human retinal pigment epithelium cells (ARPE‐19) were exposed to hypoxia for 2h, 4h, 6h, 8h and 24h. The amount of BNP and VEGF (positive control) were measured at different time points in culture media using EIA. Hypoxia‐Inducible Factor (HIF), a protein, which is the master switch in regulating all the responses to hypoxia downstream, was measured using Western blotting.Results At 24h, the amount of BNP in culture media was significantly higher in hypoxic than in normoxic conditions. Also, the concentration of both VEGF and HIF were significantly higher in hypoxia.Conclusion Hypoxia increases the release of BNP from RPE cells and the response is mediated by HIF.The present results characterize for the first time a stimulus for the natriuretic peptide system in human retina and explain previous clinical findings. Thus, the measurement of natriuretic peptides in the vitreous may guide the treatment of the intraocular diseases in which the retina is suffering from hypoxia. Future perspectives: Natriuretic peptides regulate oxygen transport in all tissues?
Cellular senescence is increased in human retinal microaneurysms during aging
Authors: MENDES‐JORGE L , LOPEZ‐LUPPO M , NACHER V , RAMOS D , NAVARRO M , CARRETERO A , RODRIGUEZ‐BAEZA A , RUBERTE J 
Published: November 2013

AbstractPurpose Different studies indicates that the presence of retinal microaneurysms, dilations of the capillaries which often appear as gross outpouchings of the vessel wall, increases during human aging. However, little is known about the mechanisms that may contribute to the development of these structures. The aim of this study was to examine whether cellular senescence may contribute to the formation of microaneurysms and specifically examine the role of p16INK4a, a cyclin dependent kinase inhibitor, that may act promoting the irreversible cell cycle arrest and senescence.Methods Human retinas were obtained from 14 old‐donors and 3 middle‐aged donors. p16INK4a expression was analyzed using immunohistochemistry and laser‐confocal microscopy. Furthermore, in the same retinas we assessed senescence‐associated β‐galactosidase (SA‐β‐gal) activity, a widely used biomarker for cellular sencescence.Results Microaneurysms were present in all the retinas obtained from old donors but were absent in those obtained from midle‐aged donors. p16INK4a expression was strongly increased in all retinal layers of old retinas when compared with middle‐aged retinas. We observed that p16INK4a expression was increased in retinal blood vessels of aged donors, in which we also detected the presence of high levels of SA‐β‐gal activity. Furthermore, p16INK4a expression was strickingly increased in retinal microaneuryms when compared with that observed in their associated capillaries.Conclusion p16INK4a was overexpressed in the retinal microaneurysms of aging people indicating that cellular senescence could be a crucial mechanism contributing to the formation of retinal microaneuryms during aging.
The fractal properties of the retinal vascular architecture
Authors: VEKRIA P , CUBBIDGE R , HEITMAR R 
Published: November 2013

AbstractPurpose The human retinal vasculature has been demonstrated to exhibit fractal, or statistically self similar properties. Fractal analysis offers a simple quantitative method to characterise the complexity of the branching vessel network in the retina. Several methods have been proposed to quantify the fractal properties of the retina.Methods Twenty five healthy volunteers underwent retinal photography, retinal oximetry and ocular biometry. A robust method to evaluate the fractal properties of the retinal vessels is proposed; it consists of manual vessel segmentation and box counting of 50 degree retinal photographs centred on the fovea.Results Data is presented on the associations between the fractal properties of the retinal vessels and various functional properties of the retina.Conclusion Fractal properties of the retina could offer a promising tool to assess the risk and prognostic factors that define retinal disease. Outstanding efforts surround the need to adopt a standardised protocol for assessing the fractal properties of the retina, and further demonstrate its association with disease processes.
Assessment of macular retinal thickness and volume in normal eyes and highly myopic eyes with spectral optical coherence tomography
Authors: CHEBIL A , BEN ACHOUR B , KORT F , CHAKER N , EL MATRI L 
Published: November 2013

AbstractPurpose To compare the macular retinal thickness and macular volume between subjects with high myopia and non‐myopiaMethods A prospective comparative study recruited highly myopic eyes with no posterior abnormalities (spherical equivalence (SE) over ‐6 dioptres (D) or AXL>or=26.5 mm) and subjects with non‐myopia (SE between 1.5D and ‐1.5 D). Macular retinal thickness and volume thickness at the fovea 1.5 mm superiorly, inferiorly, nasally, and temporally were measured with spectral‐domain optical coherence tomography (TOPCON SD 2000).Results One hundred and twelve myopic eyes and 66 non‐myopic eyes were included. The mean age of the high myopic group and non‐myopia group was 34.28 and 28.5 years old, respectively. The mean refraction was ‐13.98 D in the high myopia group and ‐0.24 D in the non‐myopia group. The high myopia group had significantly greater mean retinal thickness in the foveola 188.8 vs 155.2 microm, P<0.0001), and fovea 1 mm area (205.8 vs 181.4 microm, P=0.0088), than the non‐myopia group. The mean retinal thickness in the inner and outer macular area of the high myopia group was significantly less than in the non‐myopia group. In addition, the high myopia group had significantly smaller macular volume than the non‐myopia group (P<0.0001).Conclusion The retinal thickness in high myopic eyes is thicker in the foveola and fovea, but thinner in the inner and the outer macular region. The retina of individuals with high myopia had smaller macular volume than those with non‐myopia.