Objective: To analyze the most common ophthalmologic disorders in pregnant women seen in a hospit... more Objective: To analyze the most common ophthalmologic disorders in pregnant women seen in a hospital in Munich in Germany using a big data analysis system, as well as to compare the results obtained with those from other epidemiological studies that used different data acquisition methods. Methods: We retrospectively analyzed electronic health records of pregnant women who were seen at the ophthalmology department from 2003 to 2019 at the Ludwig-Maximilians-Universität München hospital. The main complaints that led to ophthalmic consultations during this period were evaluated, and also the variation in intraocular pressure of patients throughout gestational trimesters by analyzing data from the data warehouse system. Results: A total of 27,326 electronic health records were analyzed. Of participants, 149 (0.54%) required eye care during pregnancy. Their mean intraocular pressure was 17mmHg in the first trimester, 12mmHg in the second trimester, and 14mmHg in the third trimester. The most prevalent findings were dry eye (29.3%) and conjunctivitis (16%), and ametropia (16%). The most common posterior segment problem was diabetic retinopathy (4.6%). The lower mean intraocular pressure in the second and third trimester found in our study is in accordance with other studies that used other method for data acquisition. Conclusion: The most common ophthalmic conditions found in this study population were dry eye, conjunctivitis, and ametropia. The use of data warehouse proved to be useful for acquiring and analyzing data from many patients. This study results are comparable with other studies in published literature that adopted different methodology.
Graefes Archive for Clinical and Experimental Ophthalmology, Apr 7, 2022
Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive... more Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP). Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05. We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2–1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01). We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.
Background Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the... more Background Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear. With this work, we aim to assess the interaction of the genetic risk for AMD and the adherence to the Mediterranean diet in the Coimbra Eye Study. Methods Enrolled subjects (n = 612) underwent ophthalmological exams and answered a food questionnaire. Adherence to the Mediterranean diet was assessed with mediSCORE. An overall value was calculated for each participant, ranging from 0 to 9, using the sum of 9 food groups, and a cut off value of ≥ 6 was considered high adherence. Rotterdam Classification was used for grading. Participants’ genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The genetic risk score (GRS) was calculated for each participant cons...
Graefe's Archive for Clinical and Experimental Ophthalmology
Purpose This study reviews evidence and provides recommendations for the ideal setting of intravi... more Purpose This study reviews evidence and provides recommendations for the ideal setting of intravitreal injection (IVI) administration of vascular endothelial growth factor (VEGF) inhibitors. Methods A multi-step approach was employed, including content analysis of regulations and guidelines, a systematic literature review, and an international survey assessing perioperative complications and endophthalmitis incidence in relation to injection settings. The literature review searched PubMed and Cochrane databases from 2006 to 2022, focusing on studies reporting correlations between complications and treatment settings. The survey utilized a web-based questionnaire distributed to clinical sites and the international ophthalmic community, with data managed using electronic capture tools. Results We reviewed regulations and guidelines from 23 countries across five continents, finding significant variation in IVI administration settings. In most countries, IVI is primarily administered in...
Introduction: Exposure to blue light has seriously increased in our environment since the arrival... more Introduction: Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury. Methods: The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022.
PurposeTear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients wi... more PurposeTear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. Here, we assessed the tear fluid of nondiabetic individuals, diabetic patients with no DR, and diabetic patients with nonproliferative DR (NPDR) or with proliferative DR (PDR) to find putative biomarkers for the diagnosis and staging of DR.MethodsTear fluid samples were collected using Schirmer test strips from a cohort with 12 controls and 54 Type 2 Diabetes (T2D) patients, and then analyzed using mass spectrometry (MS)-based shotgun proteomics and bead-based multiplex assay. Tear fluid-derived small extracellular vesicles (EVs) were analyzed by transmission electron microscopy, Western Blotting, and nano tracking.ResultsProteomics analysis revealed that among the 682 reliably quantified proteins...
Objetivos: Estudar o papel de biomarcadores inflamatórios sistémicos, como fatores condicionantes... more Objetivos: Estudar o papel de biomarcadores inflamatórios sistémicos, como fatores condicionantes da resposta anátomo-funcional ao tratamento com bevacizumab no edema macular diabético (EMD) Material e métodos: estudo prospectivo que incluiu 30 doentes com EMD, tratados com injecções intravítreas de bevacizumab e com seguimento de 12 meses. Para todos os casos foi obtido um perfil analítico basal contemplando risco cardiovascular, disfunção renal, dislipidémia e controlo glicémico. Pela técnica ELISA, foram estudados os seguintes fatores pró-inflamatórios: VEGF, ICAM-1, MCP1 e TNF-α. Os valores analíticos foram correlacionados com indicadores clínicos e tomográficos durante o seguimento. Resultados: Verificamos melhoria significativa da espessura foveal central (EFC) (525.80±136.80 µm para 363.31±76.10 µm, p<0.001), bem como da acuidade visual (AV) (0.61±0.24 para 0.40±0.19 LogMAR, p<0.001). Estes resultados foram obtidos com uma média de 6.20±1.29 injecções. O valor de proteí...
Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retino... more Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1 + cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1 + cells density in the outer retina.
Large-scale genome-wide association studies (GWAS) have reported important single nucleotide poly... more Large-scale genome-wide association studies (GWAS) have reported important single nucleotide polymorphisms (SNPs) with significant associations with age-related macular degeneration (AMD). However, their role in disease development remains elusive. This study aimed to assess SNPemetabolite associations (i.e., metabolite quantitative trait loci [met-QTL]) and to provide insights into the biological mechanisms of AMD risk SNPs. Design: Cross-sectional multicenter study (Boston, Massachusetts, and Coimbra, Portugal). Participants: Patients with AMD (n ¼ 388) and control participants (n ¼ 98) without any vitreoretinal disease (> 50 years). Methods: Age-related macular degeneration grading was performed using color fundus photographs according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and evaluated with mass spectrometry for metabolomic profiling and Illumina OmniExpress for SNPs profiling. Analyses of met-QTL of endogenous metabolites were conducted using linear regression models adjusted for age, gender, smoking, 10 metabolite principal components (PCs), and 10 SNP PCs. Additionally, we analyzed the cumulative effect of AMD risk SNPs on plasma metabolites by generating genetic risk scores and assessing their associations with metabolites using linear regression models, accounting for the same covariates. Modeling was performed first for each cohort, and then combined by meta-analysis. Multiple comparisons were accounted for using the false discovery rate (FDR). Main Outcome Measures: Plasma metabolite levels associated with AMD risk SNPs. Results: After quality control, data for 544 plasma metabolites were included. Meta-analysis of data from all individuals (AMD patients and control participants) identified 28 significant met-QTL (b ¼ 0.016e0.083; FDR qvalue < 1.14 Â 10 e2), which corresponded to 5 metabolites and 2 genes: ASPM and LIPC. Polymorphisms in the LIPC gene were associated with phosphatidylethanolamine metabolites, which are glycerophospholipids, and polymorphisms in the ASPM gene with branched-chain amino acids. Similar results were observed when considering only patients with AMD. Genetic risk scoreemetabolite associations further supported a global impact of AMD risk SNPs on the plasma metabolome. Conclusions: This study demonstrated that genomicemetabolomic associations can provide insights into the biological relevance of AMD risk SNPs. In particular, our results support that the LIPC gene and the glycerophospholipid metabolic pathway may play an important role in AMD, thus offering new potential therapeutic targets for this disease.
Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic m... more Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic maculopathy based on spectral domain optical coherence tomography.Methods:The first draft of the project was developed based on previously published classifications and a literature search regarding the spectral domain optical coherence tomography quantitative and qualitative features of diabetic maculopathy. This draft was sent to an international panel of retina experts for a first revision. The panel met at the European School for Advanced Studies in Ophthalmology headquarters in Lugano, Switzerland, and elaborated the final document.Results:Seven tomographic qualitative and quantitative features are taken into account and scored according to a grading protocol termed TCED-HFV, which includes foveal thickness (T), corresponding to either central subfoveal thickness or macular volume, intraretinal cysts (C), the ellipsoid zone (EZ) and/or external limiting membrane (ELM) status (E), pre...
ObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic at... more ObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic atrophy (GA) and percentage of foveal GA.MethodsMulticenter, retrospective cross-sectional study of patients with GA due to age-related macular degeneration. Demographics, VA, fundus autofluorescence (FAF) and optical coherence tomography (OCT) images were collected. Using FAF images aided by OCT, foveal sparing status, GA pattern, total GA size, and percentage of GA covering the foveal area - area within a 1.5 mm diameter circle centered on the fovea centralis - were assessed. Univariable and multiple linear regression analyses were performed.Results54 eyes (mean age 78.7 ±7.7 (SD), 60.0% female) were studied. Mean VA was 0.8 ± 0.6 logMAR, mean total GA 8.8 ± 6.7 mm2 and mean percentage of foveal GA was 71.5 ± 30.9%. Of all assessed eyes, 48.2% (n = 26) presented with multifocal GA, and 18.5% (n = 10) had foveal sparing. Multiple regression analysis revealed that, controlling for age and ...
Current guidelines on the management of patients with neovascular age-related macular degeneratio... more Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAM...
Aims To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with pres... more Aims To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with presumed neovascular age-related macular degeneration (AMD) who were considered poor responders to ranibizumab. Methods Caucasian patients with suspected neovascular AMD, presumed to be choroidal neovascularisation, previously treated with ≥8 intravitreal injections of ranibizumab 0.5 mg (Lucentis; Novartis AG, Basel, Switzerland) administered as required during optical coherence tomography-guided dosing were retrospectively included. Eyes were categorised according to the time from injection 1 to injection 6 (group 1: <12 months; group 2: ≥12 months). Indocyanine green angiography (ICGA) was used to re-evaluate eyes for PCV. Suitable candidates received reduced-fluence photodynamic therapy/ranibizumab combination therapy supplemented by ranibizumab monotherapy, as required. Results 202 eyes were included (group 1: 73.8%; group 2: 26.2%). The prevalence of PCV in group 1 (21.5%) was significantly higher than in group 2 (3.8%; p=0.003). After initiation of combination therapy, 16 eyes with PCV received 3.1±2.5 ranibizumab injections/ year vs 8.4±2.4 injections/year before initiation of combination therapy (p<0.001). Conclusions In Caucasian patients with presumed neovascular AMD, PCV prevalence is increased in eyes that respond poorly to ranibizumab monotherapy. ICGA improved PCV diagnosis in poor responders; combination therapy may be beneficial for eyes with PCV.
21 for the EYE-RISK consortium, z and the European Eye Epidemiology (E3) consortium x Purpose: Ag... more 21 for the EYE-RISK consortium, z and the European Eye Epidemiology (E3) consortium x Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design: Meta-analysis of prevalence data. Participants: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures: Prevalence of early and late AMD, BCVA, and number of AMD cases. Results: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%e5.0%) in those aged 55e59 years to 17.6% (95% CI 13.6%e21.5%) in those aged 85 years; for late AMD these figures were 0.1% (95% CI 0.04%e0.3%) and 9.8% (95% CI 6.3%e13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer 80-year-old subjects with CNV were visually impaired (P ¼ 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. Conclusion: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of antievascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.
Objective: To analyze the most common ophthalmologic disorders in pregnant women seen in a hospit... more Objective: To analyze the most common ophthalmologic disorders in pregnant women seen in a hospital in Munich in Germany using a big data analysis system, as well as to compare the results obtained with those from other epidemiological studies that used different data acquisition methods. Methods: We retrospectively analyzed electronic health records of pregnant women who were seen at the ophthalmology department from 2003 to 2019 at the Ludwig-Maximilians-Universität München hospital. The main complaints that led to ophthalmic consultations during this period were evaluated, and also the variation in intraocular pressure of patients throughout gestational trimesters by analyzing data from the data warehouse system. Results: A total of 27,326 electronic health records were analyzed. Of participants, 149 (0.54%) required eye care during pregnancy. Their mean intraocular pressure was 17mmHg in the first trimester, 12mmHg in the second trimester, and 14mmHg in the third trimester. The most prevalent findings were dry eye (29.3%) and conjunctivitis (16%), and ametropia (16%). The most common posterior segment problem was diabetic retinopathy (4.6%). The lower mean intraocular pressure in the second and third trimester found in our study is in accordance with other studies that used other method for data acquisition. Conclusion: The most common ophthalmic conditions found in this study population were dry eye, conjunctivitis, and ametropia. The use of data warehouse proved to be useful for acquiring and analyzing data from many patients. This study results are comparable with other studies in published literature that adopted different methodology.
Graefes Archive for Clinical and Experimental Ophthalmology, Apr 7, 2022
Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive... more Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP). Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05. We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2–1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01). We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.
Background Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the... more Background Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear. With this work, we aim to assess the interaction of the genetic risk for AMD and the adherence to the Mediterranean diet in the Coimbra Eye Study. Methods Enrolled subjects (n = 612) underwent ophthalmological exams and answered a food questionnaire. Adherence to the Mediterranean diet was assessed with mediSCORE. An overall value was calculated for each participant, ranging from 0 to 9, using the sum of 9 food groups, and a cut off value of ≥ 6 was considered high adherence. Rotterdam Classification was used for grading. Participants’ genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The genetic risk score (GRS) was calculated for each participant cons...
Graefe's Archive for Clinical and Experimental Ophthalmology
Purpose This study reviews evidence and provides recommendations for the ideal setting of intravi... more Purpose This study reviews evidence and provides recommendations for the ideal setting of intravitreal injection (IVI) administration of vascular endothelial growth factor (VEGF) inhibitors. Methods A multi-step approach was employed, including content analysis of regulations and guidelines, a systematic literature review, and an international survey assessing perioperative complications and endophthalmitis incidence in relation to injection settings. The literature review searched PubMed and Cochrane databases from 2006 to 2022, focusing on studies reporting correlations between complications and treatment settings. The survey utilized a web-based questionnaire distributed to clinical sites and the international ophthalmic community, with data managed using electronic capture tools. Results We reviewed regulations and guidelines from 23 countries across five continents, finding significant variation in IVI administration settings. In most countries, IVI is primarily administered in...
Introduction: Exposure to blue light has seriously increased in our environment since the arrival... more Introduction: Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury. Methods: The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022.
PurposeTear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients wi... more PurposeTear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. Here, we assessed the tear fluid of nondiabetic individuals, diabetic patients with no DR, and diabetic patients with nonproliferative DR (NPDR) or with proliferative DR (PDR) to find putative biomarkers for the diagnosis and staging of DR.MethodsTear fluid samples were collected using Schirmer test strips from a cohort with 12 controls and 54 Type 2 Diabetes (T2D) patients, and then analyzed using mass spectrometry (MS)-based shotgun proteomics and bead-based multiplex assay. Tear fluid-derived small extracellular vesicles (EVs) were analyzed by transmission electron microscopy, Western Blotting, and nano tracking.ResultsProteomics analysis revealed that among the 682 reliably quantified proteins...
Objetivos: Estudar o papel de biomarcadores inflamatórios sistémicos, como fatores condicionantes... more Objetivos: Estudar o papel de biomarcadores inflamatórios sistémicos, como fatores condicionantes da resposta anátomo-funcional ao tratamento com bevacizumab no edema macular diabético (EMD) Material e métodos: estudo prospectivo que incluiu 30 doentes com EMD, tratados com injecções intravítreas de bevacizumab e com seguimento de 12 meses. Para todos os casos foi obtido um perfil analítico basal contemplando risco cardiovascular, disfunção renal, dislipidémia e controlo glicémico. Pela técnica ELISA, foram estudados os seguintes fatores pró-inflamatórios: VEGF, ICAM-1, MCP1 e TNF-α. Os valores analíticos foram correlacionados com indicadores clínicos e tomográficos durante o seguimento. Resultados: Verificamos melhoria significativa da espessura foveal central (EFC) (525.80±136.80 µm para 363.31±76.10 µm, p<0.001), bem como da acuidade visual (AV) (0.61±0.24 para 0.40±0.19 LogMAR, p<0.001). Estes resultados foram obtidos com uma média de 6.20±1.29 injecções. O valor de proteí...
Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retino... more Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1 + cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1 + cells density in the outer retina.
Large-scale genome-wide association studies (GWAS) have reported important single nucleotide poly... more Large-scale genome-wide association studies (GWAS) have reported important single nucleotide polymorphisms (SNPs) with significant associations with age-related macular degeneration (AMD). However, their role in disease development remains elusive. This study aimed to assess SNPemetabolite associations (i.e., metabolite quantitative trait loci [met-QTL]) and to provide insights into the biological mechanisms of AMD risk SNPs. Design: Cross-sectional multicenter study (Boston, Massachusetts, and Coimbra, Portugal). Participants: Patients with AMD (n ¼ 388) and control participants (n ¼ 98) without any vitreoretinal disease (> 50 years). Methods: Age-related macular degeneration grading was performed using color fundus photographs according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and evaluated with mass spectrometry for metabolomic profiling and Illumina OmniExpress for SNPs profiling. Analyses of met-QTL of endogenous metabolites were conducted using linear regression models adjusted for age, gender, smoking, 10 metabolite principal components (PCs), and 10 SNP PCs. Additionally, we analyzed the cumulative effect of AMD risk SNPs on plasma metabolites by generating genetic risk scores and assessing their associations with metabolites using linear regression models, accounting for the same covariates. Modeling was performed first for each cohort, and then combined by meta-analysis. Multiple comparisons were accounted for using the false discovery rate (FDR). Main Outcome Measures: Plasma metabolite levels associated with AMD risk SNPs. Results: After quality control, data for 544 plasma metabolites were included. Meta-analysis of data from all individuals (AMD patients and control participants) identified 28 significant met-QTL (b ¼ 0.016e0.083; FDR qvalue < 1.14 Â 10 e2), which corresponded to 5 metabolites and 2 genes: ASPM and LIPC. Polymorphisms in the LIPC gene were associated with phosphatidylethanolamine metabolites, which are glycerophospholipids, and polymorphisms in the ASPM gene with branched-chain amino acids. Similar results were observed when considering only patients with AMD. Genetic risk scoreemetabolite associations further supported a global impact of AMD risk SNPs on the plasma metabolome. Conclusions: This study demonstrated that genomicemetabolomic associations can provide insights into the biological relevance of AMD risk SNPs. In particular, our results support that the LIPC gene and the glycerophospholipid metabolic pathway may play an important role in AMD, thus offering new potential therapeutic targets for this disease.
Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic m... more Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic maculopathy based on spectral domain optical coherence tomography.Methods:The first draft of the project was developed based on previously published classifications and a literature search regarding the spectral domain optical coherence tomography quantitative and qualitative features of diabetic maculopathy. This draft was sent to an international panel of retina experts for a first revision. The panel met at the European School for Advanced Studies in Ophthalmology headquarters in Lugano, Switzerland, and elaborated the final document.Results:Seven tomographic qualitative and quantitative features are taken into account and scored according to a grading protocol termed TCED-HFV, which includes foveal thickness (T), corresponding to either central subfoveal thickness or macular volume, intraretinal cysts (C), the ellipsoid zone (EZ) and/or external limiting membrane (ELM) status (E), pre...
ObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic at... more ObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic atrophy (GA) and percentage of foveal GA.MethodsMulticenter, retrospective cross-sectional study of patients with GA due to age-related macular degeneration. Demographics, VA, fundus autofluorescence (FAF) and optical coherence tomography (OCT) images were collected. Using FAF images aided by OCT, foveal sparing status, GA pattern, total GA size, and percentage of GA covering the foveal area - area within a 1.5 mm diameter circle centered on the fovea centralis - were assessed. Univariable and multiple linear regression analyses were performed.Results54 eyes (mean age 78.7 ±7.7 (SD), 60.0% female) were studied. Mean VA was 0.8 ± 0.6 logMAR, mean total GA 8.8 ± 6.7 mm2 and mean percentage of foveal GA was 71.5 ± 30.9%. Of all assessed eyes, 48.2% (n = 26) presented with multifocal GA, and 18.5% (n = 10) had foveal sparing. Multiple regression analysis revealed that, controlling for age and ...
Current guidelines on the management of patients with neovascular age-related macular degeneratio... more Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAM...
Aims To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with pres... more Aims To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with presumed neovascular age-related macular degeneration (AMD) who were considered poor responders to ranibizumab. Methods Caucasian patients with suspected neovascular AMD, presumed to be choroidal neovascularisation, previously treated with ≥8 intravitreal injections of ranibizumab 0.5 mg (Lucentis; Novartis AG, Basel, Switzerland) administered as required during optical coherence tomography-guided dosing were retrospectively included. Eyes were categorised according to the time from injection 1 to injection 6 (group 1: <12 months; group 2: ≥12 months). Indocyanine green angiography (ICGA) was used to re-evaluate eyes for PCV. Suitable candidates received reduced-fluence photodynamic therapy/ranibizumab combination therapy supplemented by ranibizumab monotherapy, as required. Results 202 eyes were included (group 1: 73.8%; group 2: 26.2%). The prevalence of PCV in group 1 (21.5%) was significantly higher than in group 2 (3.8%; p=0.003). After initiation of combination therapy, 16 eyes with PCV received 3.1±2.5 ranibizumab injections/ year vs 8.4±2.4 injections/year before initiation of combination therapy (p<0.001). Conclusions In Caucasian patients with presumed neovascular AMD, PCV prevalence is increased in eyes that respond poorly to ranibizumab monotherapy. ICGA improved PCV diagnosis in poor responders; combination therapy may be beneficial for eyes with PCV.
21 for the EYE-RISK consortium, z and the European Eye Epidemiology (E3) consortium x Purpose: Ag... more 21 for the EYE-RISK consortium, z and the European Eye Epidemiology (E3) consortium x Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design: Meta-analysis of prevalence data. Participants: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures: Prevalence of early and late AMD, BCVA, and number of AMD cases. Results: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%e5.0%) in those aged 55e59 years to 17.6% (95% CI 13.6%e21.5%) in those aged 85 years; for late AMD these figures were 0.1% (95% CI 0.04%e0.3%) and 9.8% (95% CI 6.3%e13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer 80-year-old subjects with CNV were visually impaired (P ¼ 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. Conclusion: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of antievascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.
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Papers by Rufino Silva