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1.
J Clin Pathol ; 73(7): 408-412, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31771972

RESUMO

AIMS: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease. METHODS: Immunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low. RESULTS: There were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013). CONCLUSIONS: High immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.


Assuntos
Melanoma/diagnóstico , Peroxirredoxina III/metabolismo , Neoplasias Uveais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Inclusão em Parafina , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Neoplasias Uveais/metabolismo , Neoplasias Uveais/patologia , Adulto Jovem
2.
Int J Spine Surg ; 12(2): 201-240, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30276080

RESUMO

BACKGROUND: Replacement of a diseased lumbar intervertebral disc with an artificial device, a procedure known as lumbar total disc replacement (LTDR), has been practiced since the 1980s. METHODS: Comprehensive review of published literature germane to LTDR, but comment is restricted to high-quality evidence reporting implantation of lumbar artificial discs that have been commercially available for at least 15 years at the time of writing and which continue to be commercially available. RESULTS: LTDR is shown to be a noninferior (and sometimes superior) alternative to lumbar fusion in patients with discogenic low back pain and/or radicular pain attributable to lumbar disc degenerative disease (LDDD). Further, LTDR is a motion-preserving procedure, and evidence is emerging that it may also result in risk reduction for subsequent development and/or progression of adjacent segment disease. CONCLUSIONS: In spite of the substantial logistical challenges to the safe introduction of LTDR to a health care facility, the procedure continues to gain acceptance, albeit slowly. CLINICAL RELEVANCE: Patients with LDDD who are considering an offer of spinal surgery can only provide valid and informed consent if they have been made aware of all reasonable surgical and nonsurgical options that may benefit them. Accordingly, and in those cases in which LTDR may have a role to play, patients under consideration for other forms of spinal surgery should be informed that this valid procedure exists.

3.
Exp Gerontol ; 106: 80-87, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29501627

RESUMO

PURPOSE: Age related macular degeneration (AMD) is a leading cause of irreversible visual loss in developed countries. It is associated with vascular risk factors including hypertension. Dysregulated blood pressure (BP) behaviour including orthostatic hypertension (OHTN), hypotension (OH) and BP variability (BPV) are associated with end-organ damage, particularly in the brain. We investigated if abnormal orthostatic BP (OBP) was a risk factor for AMD, for which a vascular aetiology is implicated. METHODS: A nationally representative, cross-sectional study was carried out 2009/2010 in The Irish Longitudinal Study on Ageing (TILDA). Beat-to-beat BP data, measured by digital photoplethysmography during active stand, was used to characterise OBP behaviour in the 30-110 s after standing. OH, OHTN, BPV and normal stabilisation recovery phenotypes were defined. AMD was identified following masked grading of 45° monoscopic colour retinal photographs, which were centred on the macula and taken with a NIDEK AFC-210 non-mydriatic auto-fundus camera. The relationship between OBP recovery phenotypes and AMD in 3750 adults aged ≥50 years was investigated using multivariate logistic regression models, adjusted for traditional AMD risk factors. RESULTS: From 30 to 110 s post active stand, systolic and diastolic OHTN was associated with increased odds of AMD after adjustment for demographics, health behaviours including smoking, family history of AMD, self-report (SR) diabetes, SR cataracts, objective hypertension and prescribed antihypertensives. No evidence of heterogeneity of OHTN effect was found between those who were hypertensive to those who were normotensive. CONCLUSIONS: This study provides evidence that OHTN may be an independent cardiovascular risk factor for AMD.


Assuntos
Envelhecimento/patologia , Hipertensão/complicações , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Vida Independente , Irlanda/epidemiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
4.
Ophthalmic Res ; 58(1): 49-55, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27832661

RESUMO

OBJECTIVE: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. METHODS: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). RESULTS: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. CONCLUSION: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.


Assuntos
Macula Lutea/patologia , Análise de Componente Principal/métodos , Ranibizumab/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Análise Discriminante , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Oftalmoscopia , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento
5.
Int J Ophthalmol Clin Res ; 3(2)2016 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-27830188

RESUMO

AIM: To identify challenges inherent in introducing a toric intraocular lens (IOL) to a non-refractive cataract practice, and evaluate residual astigmatism achieved and its impact on patient satisfaction. METHODS: Following introduction of a toric IOL to a cataract practice with all procedures undertaken by a single, non-refractive, surgeon (SB), pre-operative, intra-operative and post-operative data was analysed. Attenuation of anticipated post-operative astigmatism was examined, and subjectively perceived visual functioning was assessed using validated questionnaires. RESULTS: Median difference vector (DV, the induced astigmatic change [by magnitude and axis] that would enable the initial surgery to achieve intended target) was 0.93D; median anticipated DV with a non-toric IOL was 2.38D. One eye exhibited 0.75D residual astigmatism, compared to 3.8D anticipated residual astigmatism with a non-toric IOL. 100% of respondents reported satisfaction of ≥ 6/10, with 37.84% of respondents entirely satisfied (10/10). 17 patients (38.63%) reported no symptoms of dysphotopsia (dysphoptosia score 0/10), only 3 respondents (6.8%) reported a clinically meaningful level of dysphotopsia (≥ 4/10). Mean post-operative NEI VF-11 score was 0.54 (+/-0.83; scale 0 - 4). CONCLUSION: Use of a toric IOL to manage astigmatism during cataract surgery results in less post-operative astigmatism than a non-toric IOL, resulting in avoidance of unacceptable post-operative astigmatism.

6.
Invest Ophthalmol Vis Sci ; 57(6): 2552-63, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27163768

RESUMO

PURPOSE: To investigate the effect of cataract (and cataract surgery) on macular pigment (MP) measurements using the Heidelberg Spectralis HRA+OCT MultiColor device. METHODS: Thirty-six patients (age, 54-87 years) scheduled for cataract surgery at the Institute of Eye Surgery, Ireland, were enrolled in this study. Cataracts were graded using the Lens Opacities Classification System (LOCS) III, and surgery was performed using standard phacoemulsification technique with implantation of a Tecnis ZCB00 or Tecnis ZCT intraocular lens. Macular pigment was measured before and after cataract surgery in the operated (study) eye and in the fellow (control) eye. RESULTS: In the study eye, there was statistically significant disagreement in measures of MP taken before and after surgery. At all eccentricities, and also for MP volume, the postsurgery measurements were significantly (P < 0.05) greater, ranging from an average 16% greater at 1.72° to an average 35% greater at 0.23° eccentricity. Eyes exhibiting large disagreement between pre- and postsurgery measurements at a given eccentricity also generally exhibited substantial disagreement at other eccentricities. Overall severity of cataract contributed to greater disagreement between pre- and postoperative measures of MP, as did grade of nuclear opalescence, nuclear color, and posterior subcapsular cataract. In control eyes, there was no statistically significant disagreement in terms of measures of MP taken before and after cataract surgery (P > 0.05 for all; 1-sample t-test). CONCLUSIONS: Macular pigment measurements using the Spectralis are affected by cataract. Accordingly, we recommend that cataract be graded when measuring MP with a device that utilizes dual-wavelength fundus autofluorescence and propose the employment of a correction factor to compensate for cataract when measuring MP.


Assuntos
Extração de Catarata , Catarata/diagnóstico , Macula Lutea/metabolismo , Pigmento Macular/metabolismo , Fotometria/instrumentação , Tomografia de Coerência Óptica/instrumentação , Idoso , Idoso de 80 Anos ou mais , Catarata/metabolismo , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
7.
Br J Ophthalmol ; 100(12): 1623-1628, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27030279

RESUMO

BACKGROUND/AIMS: To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). METHODS: AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. RESULTS: Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p<0.05) prognostic factors for vision maintenance (loss <15 letters) or vision gain (≥15 letters). Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections. There was a significant (p<0.05) association between number of injections and national reimbursement schemes and OCT. CONCLUSIONS: A number of factors that are predictive of treatment outcomes in a real-life setting were identified. Notably, the decline of treatment benefits may be linked to number of injections and a failure to visit clinicians and receive OCT as required. These findings may be helpful in guiding ophthalmologist treatment decisions under limited time and financial constraints. TRIAL REGISTRATION NUMBER: NCT01447043.


Assuntos
Degeneração Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Neovascularização Retiniana/tratamento farmacológico , Acuidade Visual/fisiologia , Idoso , Inibidores da Angiogênese/administração & dosagem , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Degeneração Macular/etiologia , Degeneração Macular/fisiopatologia , Masculino , Oftalmoscopia , Neovascularização Retiniana/complicações , Neovascularização Retiniana/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
9.
Graefes Arch Clin Exp Ophthalmol ; 253(10): 1735-44, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25968132

RESUMO

PURPOSE: To investigate subjectively reported outcomes following cataract surgery and the relationships between such outcomes in the context of falling thresholds for cataract surgery. SETTING: Large, private, non-refractive cataract practice, Institute of Eye Surgery, Whitfield Clinic, Waterford, Ireland METHODS: Pre-operative, intra-operative and post-operative data of 2552 eyes undergoing phacoemulsification and implantation of the Tecnis(R) ZCB00 1-piece intraocular lens (IOL) by a single surgeon between July 2009 and October 2013 was analysed. Patients without visually consequential ocular co-morbidity completed two validated questionnaires, designed to assess subjectively perceived visual functioning and identify symptoms of dysphotopsia following cataract surgery. RESULTS: 54.8 % of questionnaire respondents were entirely satisfied (satisfaction 10/10) post-operatively, with 83.7 % reporting satisfaction of ≥7/10. Satisfaction was positively associated with patient age and negatively associated with spectacle dependence, dysphotopsia, and function related to vision (NEI VF-11) score. The mean (±standard deviation[SD]) dysphotopsia score was 1.36 (±1.9; scale 0-10), with 40 % of respondents reporting no dysphotopsia symptoms and 9.8 % reporting clinically meaningful dysphotopsia. The mean (±SD) National Eye Institute visual function-11 (NEI VF-11) score was 0.33 (±0.53; scale 0-4) and reduced function related to vision was associated with increasing severity of dysphotopsia symptoms. When linear regression was applied, 17.5 % of the variation in functionality was attributable to symptoms of dysphotopsia. CONCLUSION: Dysphotopsia is an important determinant of a patient having difficulty with vision-related tasks following cataract surgery, and patient satisfaction is positively associated with patient age and negatively associated with spectacle in dependence, dysphotopsia and function related to the vision (NEI VF-11) score.


Assuntos
Implante de Lente Intraocular , Satisfação do Paciente/estatística & dados numéricos , Facoemulsificação , Pseudofacia/fisiopatologia , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/fisiopatologia , Comorbidade , Óculos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limiar Sensorial , Inquéritos e Questionários , Transtornos da Visão/terapia , Adulto Jovem
10.
Br J Ophthalmol ; 99(2): 220-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25193672

RESUMO

BACKGROUND/AIMS: Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. METHODS: Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. RESULTS: 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSIONS: In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. TRIAL REGISTRATION NUMBER: NCT01447043.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Canadá , Europa (Continente) , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab , Retratamento , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Venezuela , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/fisiopatologia
11.
Exp Eye Res ; 118: 1-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24056206

RESUMO

Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.


Assuntos
Biomarcadores Tumorais/análise , Melanoma/metabolismo , Proteômica/métodos , Neoplasias Uveais/metabolismo , Humanos
12.
Ophthalmology ; 120(8): 1632-40, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23562302

RESUMO

OBJECTIVE: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). DESIGN: A cross-sectional study of healthy adults aged 20 to 70. PARTICIPANTS: We recruited 302 participants after local advertisement. METHODS: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts. MAIN OUTCOME MEASURES: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender. RESULTS: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10(-4)), an SNP in high linkage disequilibrium with rs11057841 (r(2) = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. CONCLUSIONS: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.


Assuntos
Variação Genética , Luteína/sangue , Receptores Depuradores Classe B/genética , Xantofilas/sangue , Adulto , Idoso , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Feminino , Técnicas de Genotipagem , Humanos , Lipoproteínas/sangue , Luteína/genética , Masculino , Pessoa de Meia-Idade , Fotometria , Polimorfismo de Nucleotídeo Único , Retina/metabolismo , Acuidade Visual , Xantofilas/genética , Adulto Jovem , Zeaxantinas
14.
Retina ; 32(10): 2045-51, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22718150

RESUMO

BACKGROUND: To describe clinical outcomes in a series of patients with tractional cystoid macular edema, a variant of vitreomacular traction syndrome. METHODS: Twelve consecutive patients (15 eyes) with tractional cystoid macular edema of maximum diameter of ≤550 µm and presenting corrected-distance visual acuity of ≤0.3 (Snellen ≥20/40) were studied. Each patient underwent ophthalmic examination, including visual acuity testing in the logarithm of the minimal angle of resolution system, slit-lamp biomicroscopy, and optical coherence tomography. All patients were monitored at four-monthly intervals, unless a subjective change in symptoms prompted earlier follow-up. RESULTS: The mean corrected-distance visual acuity (±standard deviation) at presentation was 0.17 (Snellen 20/30) (±0.17). The mean (±standard deviation) maximum diameter of vitreofoveolar adhesion was 267 (±139) µm. After a mean follow-up of 9.2 (±7.4) months, 8 eyes exhibited spontaneous and complete posterior vitreous detachment, with resolution of the tractional cystoid macular edema and restoration of normal foveal anatomy in 6 of these eyes and persistence of a single foveal cyst in 2 of these eyes. The final corrected-distance visual acuity (±standard deviation) in the 5 eyes that underwent spontaneous and complete posterior vitreous detachment improved from 0.20 (Snellen 20/32) (±0.13) to 0.16 (Snellen 6/8) (±0.12; P = 0.53). CONCLUSION: Complete posterior vitreous detachment occurred spontaneously in 53% of eyes with tractional cystoid macular edema in this series.


Assuntos
Edema Macular/fisiopatologia , Acuidade Visual/fisiologia , Descolamento do Vítreo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica
15.
Invest Ophthalmol Vis Sci ; 53(8): 4634-43, 2012 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-22570344

RESUMO

PURPOSE: To compare the proteomic profiles of two categories of primary uveal melanoma tissue samples; those from patients who have subsequently developed metastatic disease and those who have not. METHODS: Two-dimensional difference gel electrophoresis (2D DIGE) was performed on 25 uveal melanoma tissue specimens (minimum follow-up of 7 years) comparing nine uveal melanoma tumors from patients who developed metastatic disease and 16 from those who did not. Most of the tumors which metastasized also exhibited chromosome 3 monosomy. Selected differentially expressed proteins were further followed up by immunohistochemistry and functional validation in vitro using siRNA. RESULTS: Proteomic analysis revealed 14 statistically significant differentially expressed proteins, with nine showing increased expression (PDIA3, VIM/HEXA, SELENBP1, ENO1, CAPZA1, ERP29, TPI1, PARK7, and FABP3) and five showing decreased expression (EIF2S, PSMA3, RPSA, TUBB, and TUBA1B) in uveal melanomas that subsequently metastasized compared with those that did not. Immunohistochemical analysis was performed for six of the differentially expressed proteins and gave similar results to the 2D DIGE study for two of these proteins, fatty acid-binding protein, heart-type (FABP3) and triosephosphate isomerase (TPI1). siRNA knockdown in the 92.1 uveal melanoma cell line confirmed a functional role for FABP3 and TPI1 in invasion in vitro. CONCLUSIONS: Proteomic analysis identified proteins differentially expressed in uveal melanoma that will subsequently metastasize, some of which appear to have a functional role in invasion. These results may contribute to better predictive tests (along with genetic analysis) and to the identification of new therapeutic targets.


Assuntos
Biomarcadores Tumorais/genética , Proteínas do Olho/genética , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , RNA Neoplásico/genética , Neoplasias Uveais/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Western Blotting , Proteínas do Olho/biossíntese , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Melanoma/diagnóstico , Melanoma/secundário , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase , Proteômica/métodos , Células Tumorais Cultivadas , Eletroforese em Gel Diferencial Bidimensional , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/secundário
16.
Arch Ophthalmol ; 129(9): 1155-61, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21555598

RESUMO

OBJECTIVES: To report changes in perceived visual functioning after surgery for symptomatic cataract with preoperative corrected distance visual acuity [CDVA] of 0.4 logMAR or better (Snellen equivalent, 20/50) and to investigate the relationship between any observed changes and preoperative physical characteristics and psychophysical consequences of the lens opacity and any changes in psychophysical findings after the procedure. METHODS: Eighty-five patients with cataract completed a validated questionnaire concerning functional vision satisfaction and a series of visual performance assessments before and 2 months after cataract surgery. The lens optical density and Lens Opacities Classification System III score of the cataract were recorded. Correlations between changes in the Rasch-analyzed questionnaire score and changes in visual performance after cataract surgery, as well as preoperative psychophysical measures, lens optical density, and Lens Opacities Classification System III score, were determined. RESULTS: The mean (SD) questionnaire score improved from 2.15 (0.36) to 1.54 (0.41) (P < .001). The preoperative questionnaire score (r = -0.44), preoperative mesopic glare disability [GD] (at 1.5 cycles per degree [cpd] [r = 0.34] and 3.0 cpd [r = 0.27]), and preoperative photopic GD (at 1.5 cpd [r = 0.24] and 3.0 cpd [r = 0.30]) showed statistically significant correlations with perceived improvements in visual functioning after surgery (P < .05). Changes in perceived visual functioning correlated significantly with changes in mesopic GD (at 1.5 cpd [r = -0.43] and 3.0 cpd [r = -0.28]; P < .05) and photopic GD (at 1.5 cpd [r = -0.24] and 3.0 cpd [r = -0.39]; P < .05). Neither preoperative CDVA nor change in CDVA after surgery correlated significantly with perceived improvement in visual functioning after the procedure (P > .05 for both). CONCLUSION: Psychophysical tests alternative to CDVA better represent improvements in self-reported visual functioning following removal of symptomatic nonadvanced cataract.


Assuntos
Catarata/fisiopatologia , Implante de Lente Intraocular , Facoemulsificação , Pseudofacia/fisiopatologia , Acuidade Visual/fisiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Satisfação do Paciente , Prognóstico , Refração Ocular/fisiologia , Inquéritos e Questionários , Transtornos da Visão/fisiopatologia
17.
J Cataract Refract Surg ; 37(3): 506-12, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21333875

RESUMO

PURPOSE: To evaluate the validity of a keratometry (K)-independent method of estimating effective lens position (ELP) before phacoemulsification cataract surgery. SETTING: Institute of Eye Surgery, Whitfield Clinic, Waterford, Ireland. DESIGN: Evaluation of diagnostic test or technology. METHODS: The anterior chamber diameter and corneal height in eyes scheduled for cataract surgery were measured with a rotating Scheimpflug camera. Corneal height and anterior chamber diameter were used to estimate the ELP in a K-independent method (using the SRK/T [ELP(rs)] and Holladay 1 [ELP(rh)] formulas). RESULTS: The mean ELP was calculated using the traditional (mean ELP(s) 5.59 mm ± 0.52 mm [SD]; mean ELP(h) 5.63 ± 0.42 mm) and K-independent (mean ELP(rs) 5.55 ± 0.42 mm; mean ELP(rh) ± SD 5.60 ± 0.36 mm) methods. Agreement between ELP(s) and ELP(rs) and between ELP(h) and ELP(rh) were represented by Bland-Altman plots, with mean differences (± 1.96 SD) of 0.06 ± 0.65 mm (range -0.59 to +0.71 mm; P=.08) in association with ELP(rs) and -0.04 ± 0.39 mm (range -0.43 to +0.35 mm; P=.08) in association with ELP(rh). The mean absolute error for ELP(s) versus ELP(rs) estimation and for ELP(h) versus ELP(rh) estimation was 0.242 ± 0.222 mm (range 0.001 to 1.272 mm) and 0.152 ± 0.137 mm (range 0.001 to 0.814 mm), respectively. CONCLUSION: This study confirms that the K-independent ELP estimation method is comparable to traditional K-dependent methods and may be useful in post-refractive surgery patients.


Assuntos
Câmara Anterior/patologia , Catarata/patologia , Córnea/patologia , Técnicas de Diagnóstico Oftalmológico , Lentes Intraoculares , Facoemulsificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biometria , Capsulorrexe , Humanos , Implante de Lente Intraocular , Pessoa de Meia-Idade , Fotografação , Estudos Prospectivos , Refração Ocular/fisiologia , Acuidade Visual/fisiologia
18.
J Cataract Refract Surg ; 36(7): 1081-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20610083

RESUMO

PURPOSE: To quantify the effect on refractive outcomes after cataract surgery of personalization of Haigis intraocular lens (IOL) constants for a given surgeon-IOL combination. SETTING: Institute of Eye Surgery and Institute of Vision Research, Whitfield Clinic, Butlerstown North, Waterford, Ireland. METHODS: Personalization of Haigis IOL constants was performed using a series of 248 suitable eyes after biometry by partial coherence interferometry (IOLMaster) and IOL prediction based on optimized IOL constants derived from pooled data from the User Group for Laser Interference Biometry web site. A mean error of prediction and a mean absolute error were then calculated using the personalized IOL constants and compared with those derived using optimized IOL constants, allowing evaluation and quantification of the maximum realizable refractive benefits (if any) of personalization. RESULTS: There was no statistically significant difference between personalized and optimized Haigis IOL constants in absolute error or the proportion of eyes within +/-1.00 diopters (D), +/-0.50 D, or +/-0.25 D of the target postoperative refraction in all eyes, short eyes (axial length [AL] <22 mm; n = 19), average eyes (AL > or =22 mm and <24.5 mm; n = 149), or long eyes (AL >24.5 mm; n = 46) (all P>.05, McNemar test). Ten eyes with a short AL had a smaller absolute error (by > or =0.30 D) in association with personalized IOL constants. CONCLUSION: Personalized Haigis IOL constants showed marginal, but statistically nonsignificant, refractive advantages over optimized Haigis IOL constants, but only in eyes with a short AL. FINANCIAL DISCLAIMER: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Extração de Catarata , Lentes Intraoculares , Pseudofacia/fisiopatologia , Refração Ocular/fisiologia , Idoso , Biometria , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Interferometria , Implante de Lente Intraocular , Masculino , Padrões de Prática Médica , Inquéritos e Questionários
19.
Invest Ophthalmol Vis Sci ; 51(12): 6722-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20592234

RESUMO

PURPOSE: To investigate the relationship between specific macular pigment (MP) spatial profiles and risk factors for age-related macular degeneration (AMD). METHODS: The MP spatial profile of 484 healthy subjects was measured with customized heterochromatic flicker photometry (cHFP) and categorized into one of two profile types: typical exponential or atypical "central dip." Data on risk factors for AMD were obtained with a general health and lifestyle questionnaire. Dietary and serum concentrations of lutein (L) and zeaxanthin (Z) were also assessed. RESULTS: The presence of the central dip MP spatial profile was significantly more common in older subjects (the mean ± SD age of subjects with a central dip MP spatial profile was 46.9 ± 12 years, whereas the mean age of subjects with a typical MP spatial profile was 41.8 ± 12 years; P = 0.004) and in current cigarette smokers (P = 0.031). Also, there was a significant age-related decline in central MP optical density (MPOD; 0.25° retinal eccentricity), but in the men only (r = -0.146, P = 0.049). CONCLUSIONS: A central dip in the MP spatial profile, seen in older subjects and in cigarette smokers, may represent an undesirable feature of macular pigmentation. Further research is needed in this area.


Assuntos
Envelhecimento/fisiologia , Luteína/metabolismo , Macula Lutea/metabolismo , Degeneração Macular/metabolismo , Pigmentos da Retina/metabolismo , Fumar/metabolismo , Xantofilas/metabolismo , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Cromatografia Líquida de Alta Pressão , Cor de Olho/fisiologia , Comportamento Alimentar , Feminino , Humanos , Degeneração Macular/etiologia , Masculino , Pessoa de Meia-Idade , Fotometria/instrumentação , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem , Zeaxantinas
20.
Clin Exp Ophthalmol ; 38(3): 255-65, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20447121

RESUMO

PURPOSE: To report the value of dual biometry in the detection of biometry errors. METHODS: Study 1: retrospective study of 224 consecutive cataract operations. The intraocular lens power calculation was based on immersion biometry. Study 2: immersion biometry was compared with optical coherence biometry (OCB) in terms of axial length, anterior chamber depth, keratometry readings and the recommended lens power to achieve emmetropia. Study 3: prospective study of 61 consecutive cataract operations. Both immersion and OCB were performed, but lens power calculation was based on the latter. RESULTS: Study 1: 115 (86%), 101 (75.4%), 90 (67.2%) and 50 (37.3%) of postoperative spherical equivalents were within +/-1.5 dioptres (D), +/-1.25 D, +/-1 D and +/-0.5 D of the target, respectively. Study 2: excellent agreement between axial length readings, anterior chamber depth readings and keratometry readings by immersion biometry and OCB was observed (reflected in a mean bias of -0.065 mm, -0.048 mm and +0.1803 D, respectively, in association with OCB). Agreement between the lens power recommended by each technique to achieve emmetropia was poor (mean bias of +1.16 D in association with OCB), but improved following appropriate modification of lens constants in the Accutome A-scan software (mean bias with OCB = -0.4 D). Study 3: 37 (92.5%) and 23 (57.5%) of operated eyes achieved a postoperative refraction within +/-1 D and +/-0.5 D of target, respectively. CONCLUSION: Systematic errors in biometry can exist, in the presence of acceptable postoperative refractive results. Dual biometry allows each biometric parameter to be scrutinized in isolation, and identify sources of error that may otherwise go undetected.


Assuntos
Extração de Catarata/métodos , Implante de Lente Intraocular/estatística & dados numéricos , Erros de Refração/fisiopatologia , Erros de Refração/terapia , Biometria/métodos , Humanos , Período Intraoperatório , Monitorização Intraoperatória , Período Pós-Operatório , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Refração Ocular/fisiologia , Erros de Refração/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia/métodos
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