A review of capture-recapture methods and its possibilities in ophthalmology and vision sciences

Epidemiological information is expected to be used to develop key aspects of eye care such as to control and minimise the impact of diseases, to allocate resources, to monitor public health actions, to determine the best treatment options and to forecast the consequence of diseases in populations. Epidemiological studies are expected to provide information about the prevalence and/or incidence of eye diseases or conditions. To determine prevalence is necessary to perform a cross-sectional screening of the population at risk to ascertain the number of cases.The aim of this review is to describe and evaluate capture-recapture methods (or models) to ascertaining the number of individuals with a disease (e.g. diabetic retinopathy) or condition (e.g. vision impairment) in the population.The review covers the fundamental aspects of capture-recapture methods that would enable non-experts in epidemiology to use it in ophthalmic studies. The review provides information about theoretical aspects of the method with examples of studies in ophthalmology in which it has been used. We also provide a problem/solution approach for limitations arising from the lists obtained from registers or other reliable sources.We concluded that capture-recapture models can be considered reliable to estimate the total number of cases with eye conditions using incomplete information from registers. Accordingly, the method may be used to maintain updated epidemiological information about eye conditions helping to tackle the lack of surveillance information in many regions of the globe.- This study was supported by FCT (COMPETE/QREN) grant reference [PTDC/DPT-EPI/0412/2012] in the context of the Prevalence and Costs of Visual Impairment in Portugal: a hospital-based study (PCVIP-study) and FCT Strategic Funding UID/FIS/04650/2013. PLR is funded by FCT (COMPETE/QREN) grant reference [SFRH/BD/119420/2016]

Predicting participation of people with impaired vision in epidemiological studies

The characteristics of the target group and the design of an epidemiologic study, in particular the recruiting methods, can influence participation. People with vision impairment have unique characteristics because those invited are often elderly and totally or partially dependent on help to complete daily activities such as travelling to study sites. Therefore, participation of people with impaired vision in studies is less predictable than predicting participation for the general population.This study was supported by FCT (COMPETE/QREN) grant reference PTDC/DPT-EPI/0412/2012 in the context of the Prevalence and Costs of Visual Impairment in Portugal: a hospital based study (PCVIP-study). PLR is funded by FCT (COMPETE/QREN) grant reference SFRH/BD/119420/2016

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR. Copyright

Cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture–recapture: [SV] Tvärsnittsstudie som undersöker prevalensen och orsakerna till synnedsättning i nordvästra Portugal med hjälp av infångning-återfångst[PT] Estudo transversal que investiga a prevalência e as causas da deficiência visual no Noroeste de Portugal utilizando captura-recaptura

Objectives: The aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal. Setting Information about people with VI was obtained from primary care centres, blind association (ACAPO) and from hospitals (the PCVIP study) in the Northwest of Portugal during a period spanning years 2014–2015. Causes of VI were obtained from hospitals. Participants Administrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20° were investigated. Capture–recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources. Primary and secondary outcome measures Log-linear models were used to estimate the crude prevalence and the category specific prevalence of VI. Results Crude prevalence of VI was 1.97% (95% CI 1.56% to 2.54%), and standardised prevalence was 1% (95% CI 0.78% to 1.27%). The age-specific prevalence was 3.27% (95% CI 2.36% to 4.90%), older than 64 years, 0.64% (95% CI 0.49% to 0.88%), aged 25–64 years, and 0.07% (95% CI 0.045% to 0.13%), aged less than 25 years. The female-to-male ratio was 1.3, that is, higher prevalence among females. The five leading causes of VI were diabetic retinopathy, cataract, age-related macular degeneration, glaucoma and disorders of the globe. Conclusions The prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterise temporal changes in prevalence of VI in Portugal.No data are available. Raw data can be requested from the first author.Mål: Syftet med denna studie var att uppskatta förekomsten av och orsakerna till synnedsättning i Portugal. Studieplats: Information om personer med VI erhölls från primärvårdscentraler, blindassociation (ACAPO) och från sjukhus (PCVIP-studien) i nordvästra Portugal under en period som sträckte sig över åren 2014–2015. Orsaker till synnedsättning erhölls från sjukhus. Deltagare: Administrativa och medicinska journaler för personer med synskärpa i det bättre seende ögat på 0,5 decimal (0,30logMAR) eller sämre och/eller synfält mindre än 20° undersöktes. Capture-recapture med log-linjära modeller användes för att uppskatta antalet individer som saknas i listor över fall som erhållits från tillgängliga källor. Primära och sekundära utfallsmått: Log-linjära modeller användes för att uppskatta den råa prevalensen och den kategorispecifika prevalensen av synnedsättning. Resultat: Rå prevalens av synnedsättning var 1,97% (95% CI 1,56% till 2,54%), och standardiserad prevalens var 1% (95% CI 0,78% till 1,27%). Den åldersspecifika prevalensen var 3,27% (95% CI 2,36% till 4,90%), äldre än 64 år, 0,64% (95% CI 0,49% till 0,88%), i åldern 25–64 år och 0,07% (95% CI 0,045% till 0,13%), i åldern under 25 år. Förhållandet mellan kvinnor och män var 1,3, det vill säga högre prevalens bland kvinnor. De fem främsta orsakerna till synnedsättning var diabetisk retinopati, grå starr, åldersrelaterad makuladegeneration, glaukom och störningar i världen. Slutsatser: Prevalensen av synnedsättning i Portugal låg inom det förväntade intervallet och i linje med andra europeiska länder. Ett betydande antal fall av synnedsättning kan bero på fall som kan förebyggas, och därför verkar en minskning av prevalensen av synnedsättning i Portugal möjlig. Kvinnor och gamla människor var mer benägna att ha synnedsättning och därför kräver dessa grupper extra uppmärksamhet. Framtida studier är nödvändiga för att karakterisera tidsmässiga förändringar i prevalensen av synnedsättning i Portugal. *Detta abstrakt har maskinöversatts, osäkerheter kan uppståObjetivos: O objetivo deste estudo foi estimar a prevalência e as causas da deficiência visual em Portugal. Local de realização do estudo: Informação sobre pessoas com deficiência visual foi obtida a partir de centros de cuidados primários, associação ACAPO e de hospitais (via estudo PCVIP) no Noroeste de Portugal durante um período que se estendeu entre 2014 e 2015. As causas do deficiência visual foram obtidas apenas nos hospitais. Participantes: Foram investigados registos administrativos e médicos de pessoas com acuidade visual no melhor olho de 0,5 decimal (0,30logMAR) ou pior e/ou campo visual inferior a 20°. Foi aplicado o metodo de captura-recaptura com modelos log-linear para estimar o número de pessoas que não constavam em nenhuma das listas de casos obtidos a partir de fontes disponíveis. Resultados primários e secundários: Foram utilizados modelos log-linear para estimar a prevalência bruta e a prevalência específica da deficiência visual. Resultados: A prevalência bruta de deficiência visual foi de 1,97% (95% CI 1,56% para 2,54%), e a prevalência padronizada foi de 1% (95% 1,78% para 1,27%). A prevalência específica da idade foi de 3,27% (95% CI 2,36% a 4,90%), mais de 64 anos, 0,64% (95% CI 0,49% para 0,88%), com idades compreendidas entre os 25 e os 64 anos e 0,07% (95% CI 0,045% para 0,13%), com menos de 25 anos. A racio entre mulheres e homens foi de 1,3, ou seja, maior prevalência no sexo feminino. As cinco principais causas de deficiência visual foram a retinopatia diabética, catarata, degeneração macular relacionada com a idade, glaucoma e desordens do globo. Conclusões: A prevalência de deficiência visual em Portugal estava dentro do intervalo esperado e em linha com outros países europeus. Um número significativo de casos de deficiência visual pode estar relacionados com causas evitáveis e, portanto, uma redução da prevalência de deficiência visual em Portugal parece possível. As mulheres e os idosos são mais propensos a ter deficiência visual e, por conseguinte, estes grupos exigem uma atenção extra. São necessários mais estudos para caracterizar as mudanças temporais na prevalência de deficiência visual em Portugal.Is included in the dissertation as a submitted manuscript titled: "Prevalence and causes of vision impairment in Norwest Portugal: a capture and recapture study"</p

Trends in Glaucoma Surgical Procedures in Portugal: A 16-Year Nationwide Study (2000-2015)

PURPOSE: Glaucoma leads as the first cause of irreversible blindness. The number of patients will greatly increase in upcoming years and changes will have to be accomplished to cope with those numbers. As such, data are important to understand the effect of new policies introduced in glaucoma management. Only few countries have described their glaucoma surgical profile and, in Europe, only the United Kingdom described the last 15 years. The aim of this study is to assess the glaucoma surgical profile and its changes in mainland Portugal from 2000 to 2015. METHODS: Retrospective database analysis of inpatient and surgical outpatients' episodes of all public hospitals in mainland Portugal was performed. The annual absolute numbers of ophthalmic procedures, as well as their surgical rate (per 100,000 inhabitants) were calculated. RESULTS: Glaucoma patients undergoing glaucoma procedures were 67±14 years old and 50% were female. During the study period there was an increase in the number and surgical rate of glaucoma procedures. Trabeculectomy showed a stable surgical rate (7 per 100,000 inhabitants) despite a reduction in terms of relative weight among glaucoma procedures. At the same time, the surgical rate of glaucoma drainage devices and cyclophotoablation increased, while remaining stable for cyclocryoablation. CONCLUSIONS: In Portugal, trabeculectomy had a stable surgical rate throughout the study period, being the most performed glaucoma surgical procedure. Other surgeries, like glaucoma drainage devices and cyclophotoablation are gaining ground among glaucoma specialists. Our results match what has been published by other countries worldwide and can be used to achieve a better health planning.status: publishe

Metabolomic profiling of aqueous humor from glaucoma patients - The metabolomics in surgical ophthalmological patients (MISO) study

Glaucoma is still a poorly understood disease with a clear need for new biomarkers to help in diagnosis and potentially offer new therapeutic targets. We aimed to determine if the metabolic profile of aqueous humor (AH) as determined by nuclear magnetic resonance (NMR) spectroscopy allows the distinction between primary open-angle glaucoma patients and control subjects, and to distinguish between high-tension (POAG) and normal-tension glaucoma (NTG). We analysed the AH of patients with POAG, NTG and control subjects (n = 30/group). 1H NMR spectra were acquired using a 400 MHz spectrometer. Principle component analysis (PCA), machine learning algorithms and descriptive statistics were applied to analyse the metabolic variance between groups, identify the spectral regions, and hereby potential metabolites that can act as biomarkers for glaucoma. According to PCA, fourteen regions of the NMR spectra were significant in explaining the metabolic variance between the glaucoma and control groups, with no differences found between POAG and NTG groups. These regions were further used in building a classifier for separating glaucoma from control patients, which achieved an AUC of 0.93. Peak integration was performed on these regions and a statistical analysis, after false discovery rate correction and adjustment for the different perioperative topical drug regimen, revealed that five of them were significantly different between groups. The glaucoma group showed a higher content in regions typical for betaine and taurine, possibly linked to neuroprotective mechanisms, and also a higher content in regions that are typical for glutamate, which can indicate damaged neurons and oxidative stress. These results show how aqueous humor metabolomics based on NMR spectroscopy can distinguish glaucoma patients from controls with a high accuracy. Further studies are needed to validate these results in order to incorporate them in clinical practice.status: publishe

Unexplained Visual Loss After Silicone Oil Removal: A 7-Year Retrospective Study

INTRODUCTION: Unexplained visual loss after removal of silicone oil from the eye has been described. The purpose of this study is to determine the incidence of unexplained loss of visual acuity after SO removal and to provide possible explanations for this phenomenon. METHODS: This retrospective study included patients that underwent vitreoretinal surgery, at Centro Hospitalar São João, between January of 2012 and October of 2018. Inclusion criterion was vitreoretinal surgery in which the chosen endotamponade was SO, followed by removal of SO and exchange with balanced salt solution (BSS) or air. After SO removal, patients with documented loss of best corrected visual acuity (BCVA) on two or more Snellen lines were analyzed and patients in which the cause of the visual loss was identified, namely OHT (intraocular pressure > 21 mmHg), retinal re-detachment, glaucoma, retinal proliferative membrane formation, or corneal decompensation, were excluded. All patients with unexplained visual loss underwent spectral domain optical coherence tomography (SD-OCT) to exclude causes of visual reduction such as cystoid macular edema, epiretinal membrane, or ellipsoid/interdigitation zone disruption. A p value less than 0.05 was considered statistically significant. RESULTS: A total of 46 eyes underwent SO tamponade and SO removal during the study period. In 34.8% of the cases (n = 16) there was visual acuity loss in at least two Snellen lines. Of 46 eyes, 23.9% (n = 11) showed vision loss due to known secondary causes. Unexplained loss of visual acuity after SO removal occurred in 10.9% of cases. OHT during silicone endotamponade (p = 0.046) and silicone emulsification (p = 0.001) were identified as factors associated with unexplained visual loss after SO removal. CONCLUSION: Unexplained loss of visual acuity after SO removal occurred in 10.9% of cases. OHT during silicone endotamponade and SO emulsification were identified as important factors in the ethology of this phenomenon.status: publishe

Heterogeneity in arterial hypertension and ocular perfusion pressure definitions: Towards a consensus on blood pressure-related parameters for glaucoma studies

PURPOSE: Glaucoma studies have long taken into account the blood pressure (BP) status of patients. This study summarizes and evaluates the impact of the different criteria that have been used for BP-related variables in glaucoma research. METHODS: Studies included in two meta-analyses that reviewed the role of BP in glaucoma were analyzed. Additional studies published after the search periods of the meta-analyses were also included. Criteria for the definition of arterial hypertension and other BP-related variables, such as mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP), were retrieved. RESULTS: Sixty-four studies were evaluated. One-third used 140 mmHg as a systolic BP cut-off to define hypertension, 20% used 160 mmHg and the remaining half used various other criteria. Less than 20% of studies reported MAP and/or MOPP. While eight of the ten studies reporting MAP used a correct formula that only happened for five of the eleven studies reporting MOPP. Using as an example average blood pressure values, incorrectly used formulas could have led to an overestimation of more than 100% of the expected values. CONCLUSION: Considerable heterogeneity exists in BP-related variables in glaucoma research and different definitions can lead to large disparities. Glaucoma research would benefit from a consensus regarding blood pressure parameters.status: publishe

Improved discrimination between normal-tension and primary open-angle glaucoma with advanced vascular examinations - the Leuven Eye Study

PURPOSE: Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal-tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open-angle glaucoma (POAG). METHODS: The Leuven Eye Study database (182 NTG and 202 POAG patients; similar structural and functional damage) was used to compute three multivariate logistic regression models: a conventional model (conventional parameters only, including vascular-related self-reported phenomena, such as migraine or peripheral vasospasm); an advanced vascular model (advanced vascular parameters only: colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness); and a global model, in which both types of parameters were allowed. Receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated and compared between models. RESULTS: Patients with NTG had a higher resistive index and lower early systolic acceleration (ESA) in their retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation difference. The global model (AUC 0.743) showed a significantly better discriminative ability when compared to either the conventional (AUC 0.687, p = 0.049) or the advanced vascular (AUC 0.677, p = 0.005) models. Also, the conventional and the advanced vascular models showed a similar discriminative ability (p = 0.823). CONCLUSION: Patients with NTG have more signs of vascular dysfunction. Clinical conventional parameters, such as asking simple vascular-related questions, combined with advanced vascular examinations provide information to better understand the value that non-IOP-related factors play in NTG.status: publishe

A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy

Purpose. Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. Methods. A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. Results. After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). Conclusions. These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis