Visual Screening Method Research Articles

Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India

Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies.

Reining in RNA

Figure 1. The first joint EMBO/FASEB Workshop on Intracellular RNA Localization and Localized Translation took place between 1 and 6 July 2007, in Il Ciocco, Italy, and was organized by A. Ephrussi, E. Gavis, D. Ish‐Horowicz and J. Richter. Originally a biannual FASEB summer research conference, it is anticipated that the joint meeting will in future alternate between sites in Europe and the USA. Intracellular RNA localization and localized translation are involved in diverse processes such as embryonic patterning in Drosophila , jellyfish, tunicates, frogs and fish; the asymmetrical partitioning of fates in Drosophila neural stem cells and yeast mating types; fibroblast and neuronal growth cone motility; and synapse function (St Johnston, 2005; Du et al , 2007; Jambhekar & Derisi, 2007). The subjects discussed at this meeting included structural insights into RNA localization, improved methods for live imaging of RNA transport, and the combination of genome‐wide screens and biochemical approaches to identify localized RNAs and localization factors. Here, we highlight some of the crucial findings that were presented. Drosophila melanogaster has been widely used as a model organism to study mRNA localization and localized translation. This reflects the importance of these processes during Drosophila embryogenesis and the success of genetic screens in this organism. Indeed, visual screening methods continue to be used for the identification of new localization factors. For example, in a screen for new factors controlling microtubule organization in the fly oocyte, A. Guichet (Paris, France) found that the phosphatidylinositol‐4‐phosphate 5‐kinase (PIP5K) Skittles is necessary for phosphatidylinositol 4,5‐bisphosphate (PIP2) production and subsequent microtubule polarization, as well as for actin organization at the cortex. A. Ephrussi (Heidelberg, Germany) used a protein‐trap screen to identify Drosophila heterogeneous nuclear ribonucleoprotein 1/polypyrimidine tract binding protein 1 (hnRNP1/PTB) as a new component of the oskar ( osk ) RNP complex. Oocytes of ptb mutants show …

Pilot Study of Rapid Caries Treatment Needs Screening – A Brief Communication

To evaluate a newly developed screening method for caries-related treatment needs. The Rapid Caries Treatment Needs Screening (RCTNS) Index includes five ordinal nominal scores. Comparisons with conventional examinations were conducted among 565 young Israeli adults (aged 23 +/- 5.3 years) by the same dentist. According to conventional examination, 79.5 percent demonstrated caries-related treatment needs as compared to 54.9 percent according to RCTNS. The sensitivity of RCTNS was 68.1 percent; specificity was 96.5 percent; positive predictive value was 98.7 percent; and negative predictive value was 43.9 percent. The calculated percentage of explained variance (R2) Of the conventional examination results according to RCTNS was 55.6 percent. The data reveal the relevance of a rapid visual screening method for caries-related treatment needs. This is a pilot study that demands further methodological refinement. Preliminary results revealed a potential, which should be further investigated.

Cervical cancer prevention strategies in the developing world

Cervical cancer prevention strategies in the developing world

CHAPTER 10 A public health approach to cervical cancer control: Considerations of screening and vaccination strategies

Cervical cancer remains a leading cause of cancer death among women living in low-resource settings. In the last 3 decades, cytologic screening has —in theory —been available and yet more than 6 million women have died of this preventable disease. The necessary resources, infrastructure, and technological expertise, together with the need for repeated screenings at regular intervals, make cytologic screening difficult to implement in poor countries. As noncytologic approaches for the detection of HPV, simple visual screening methods for anogenital lesions caused by HPV, and the availability of an HPV-16/18 vaccine will enhance the linkage between screening and treatment, multiple factors will need to be considered when designing new, or modifying existing prevention strategies. Countryspecific decisions regarding the best strategy for cervical cancer control will need to rely on data from many sources and take into account complex epidemiologic, economic, social, political, and cultural factors, and be made despite uncertainty and incomplete information. A rigorous decision analytic approach using computerbased modeling methods enables linkage of the knowledge gained from empirical studies to real-world situations. This chapter provides an introduction to these methods, reviews lessons learned from cost-effectiveness analyses of cervical cancer screening in developed and developing countries, and emphasizes important qualitative themes to consider in designing cervical cancer prevention policies.

Concentration and localization of zinc during seed development and germination in wheat

In a field experiment, the effect of foliar Zn applications on the concentration of Zn in seeds of a bread wheat cultivar (Triticum aestivum L. cv. Balatilla) was studied during different stages of seed development. In addition, a staining method using dithizone (DTZ: diphenyl thiocarbazone) was applied to (1) study the localization of Zn in seeds, (2) follow the remobilization of Zn during germination, and (3) develop a rapid visual Zn screening method for seed and flour samples. In all seed development stages, foliar Zn treatments were effective in increasing seed Zn concentration. The highest Zn concentration in the seeds was found in the first stage of seed development (around the early milk stage); after this, seed Zn concentration gradually decreased until maturity. When reacting with Zn, DTZ forms a redcolored complex. The DTZ staining of seed samples revealed that Zn is predominantly located in the embryo and aleurone parts of the seeds. After 36 h of germination, the coleoptile and roots that emerged from seeds showed very intensive red color formation and had Zn concentrations up to 200 mg kg−1, indicating a substantial remobilization of Zn from seed pools into the developing roots (radicle) and coleoptile. The DTZ staining method seems to be useful in ranking flour samples for their Zn concentrations. There was a close relationship between the seed Zn concentrations and spectral absorbance of the methanol extracts of the flour samples stained with DTZ. The results suggest that (1) accumulation of Zn in seeds is particularly high during early seed development, (2) Zn is concentrated in the embryo and aleurone parts, and (3) the DTZ staining method can be used as a rapid, semiquantitative method to estimate Zn concentrations of flour and seed samples and to screen genotypes for their Zn concentrations in seeds.

Rapid detection of fungal endophytes in grasses for large‐scale studies

Summary Standard visual screening methods for determining the qualitative and quantitative presence of fungal endophytes are too time‐consuming for large‐scale ecological studies. We investigated whether commercially available immunoblot kits, using monoclonal antibody techniques and designed for rapid‐screening of the presence of Neotyphodium endophytes in fresh samples of the pasture grasses Festuca arundinacea and Lolium perenne, could be used for Neotyphodium detection using other grasses and preserved samples. We also determined whether immunoblot kits could provide quantitative information about the amount of Neotyphodium in the grass. The kits accurately detected endophyte presence in F. rubra, F. ovina, F. pratensis and F. altaica, in both preserved samples (dried and fixed), including 12‐year‐old stored, dried samples of F. rubra. Endophytes were detected in 7‐day‐old seedlings of Lolium perenne, 3 days (30%) earlier than previously recognized. The intensity of the coloured tissue prints on scanned immunoblot cards was significantly positively correlated with hyphal density, demonstrating a previously unrecognized accurate quantitative application. These findings greatly reduce logistical barriers to large‐scale field research into the broader ecological significance of Neotyphodium in temperate and arctic grasses in non‐agricultural ecosystems (particularly in remote areas) and suggest potential for estimating historical infection rates using stored and herbarium specimens.

A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast

Recently synthesized proteins are sorted at the trans-Golgi network into specialized routes for exocytosis. Surprisingly little is known about the underlying molecular machinery. Here, we present a visual screen to search for proteins involved in cargo sorting and vesicle formation. We expressed a GFP-tagged plasma membrane protein in the yeast deletion library and identified mutants with altered marker localization. This screen revealed a requirement of several enzymes regulating the synthesis of sphingolipids and ergosterol in the correct and efficient delivery of the marker protein to the cell surface. Additionally, we identified mutants regulating the actin cytoskeleton (Rvs161p and Vrp1p), known membrane traffic regulators (Kes1p and Chs5p), and several unknown genes. This visual screening method can now be used for different cargo proteins to search in a genome-wide fashion for machinery involved in post-Golgi sorting.

Training for cervical cancer prevention programs in low-resource settings: Focus on visual inspection with acetic acid and cryotherapy

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

The current status of visual disability in the elderly population of Taiwan

This study was conducted to explore the prevalence and the associated factors of visual impairment and blindness among the elderly Taiwanese population. A nationwide population-based visual health care screening program of elderly people aged 65 years or older was conducted between 1 July 2002 and 31 December 2002 in Taiwan. Based on the same standardized protocol used by the Bureau of Health Promotion, Department of Health, and a stratified random sampling design, 3160 out of 5000 elderly subjects were selected by a two-stage visual care screening method. The overall response rate was 63.2%. The mean age of the elderly participants was 72.4 +/- 5.1 years. The overall prevalence of glaucoma, corneal diseases, trauma, cataracts, myopic or diabetic retinopathy, and age-related macular degeneration among the elderly population was 2.1%, 6.3%, 0.9%, 60.2%, 7.5%, and 2.9%, respectively. The overall prevalence of visual disability (visual acuity of the better eye <0.5) was 17.7%, including 17.1% with visual impairment and 0.6% with blindness. Based on logistic regression, the significant independent factors of visual disability (visual impairment plus blindness) were sex (male vs. female, odds ratio (OR) = 0.62, 95% confidence interval (CI), 0.51-0.76), age (70-74 years vs. 65-69 years, OR = 1.60, 95% CI, 1.24-2.06; 75-79 years vs. 65-69 years, OR = 2.52, 95% CI, 1.92-3.32, > or =80 yrs vs. 65-69 yrs, OR = 4.86, 95% CI, 3.52-6.70), corneal diseases (OR = 2.26, 95% CI, 1.61-3.16), myopic or diabetic retinopathy (OR = 1.69, 95% CI, 1.20-2.39), age-related macular degeneration (OR = 4.96, 95% CI, 3.16-7.78), and cataract (OR = 3.40, 95% CI, 2.67-4.33). The geographic difference in the prevalence of vision-related eye disease, visual impairment, and blindness point to the importance of taking actions that suit local circumstances. Our results also revealed that visual impairment and blindness are important visual health problems in the elderly Taiwanese population. Age-related macular degeneration, cataracts, corneal diseases, myopic or diabetic retinopathy, female sex, and aging were the leading causes of visual disability. Further organized preventive strategies for eye care are recommended in this population.

The optomotor response: A robust first-line visual screening method for mice

In both scotopic and photopic conditions, the rotation of a grating was found to elicit head movements in mice. The highest spatial frequency eliciting this optomotor response provided an estimate of visual acuity. In male C57BL/6J mice, visual acuity increased from 0.26 cpd in scotopic conditions to 0.52 cpd in photopic conditions whereas it was 0.52 cpd in both sets of conditions in 129/SvPas mice. No optomotor response was detected in albino CD1 mice and rd1 retinal degeneration mice although light sensitivity in CD1 mice was attested by photophobia and normal electroretinograms. This rapid and cheap method could provide a powerful test of visual performance in genetically modified and pharmacologically treated mice.

Amiodarone and optic neuropathy.

To investigate the clinical, perimetric, contrast sensitivity and visual evoked potentials findings in patients on longterm treatment with amiodarone. We enrolled 14 patients (age range 47-78 years, mean age 62.7 years) on chronic amiodarone therapy (mean cumulative dose of 519 g), and 14 age-matched control subjects. Participants were submitted to ophthalmological examination, kinetic visual field testing (Goldmann), standard achromatic automated perimetry (central 30-2, Humphrey), computerized isoluminant chromatic contrast sensitivity (CCS) and pattern visual evoked potentials evaluation (VEP). Data from baseline, 6-month and 1-year follow-up examinations were analysed. The main outcome measures were: initial and final corrected visual acuity; corneal, optic disc and fundus abnormalities; mean deviation (MD) and pattern standard deviation (PSD) central 30-2 perimetry parameters; visual field loss on kinetic perimetry; indices of CCS (tritan, protan and deutan axes), and pattern VEP latency (L-VEP) and VEP amplitude (a-VEP). We found a statistically significant difference between the patients and controls' baseline L-VEP and a-VEP measurements (p < 0.001). We found no significant correlation between prolonged L-VEP and duration of amiodarone use (r = 0.07). After a 1-year follow-up, we evidenced an average increment in L-VEP of 1.96 ms and a-VEP measurements showed a decline of 0.69 micro V. In cumulative dose-specific analyses, mean differences between baseline and 12-month L-VEP measurements were more evident in those taking higher than 200 g cumulative amiodarone doses (p = 0.03). We found abnormal tritan CCS results in 19 eyes (68%). Of these, four eyes belonged to patients with no ocular disease (diabetes, cataracts). No significant differences were observed between the baseline and 12-month clinical eye examinations, central 30-2 perimetry and CCS results. We found a significant prolongation in pattern L-VEP and a significant reduction in pattern a-VEP in patients on longterm treatment with amiodarone compared to control subjects. Nevertheless, current data are insufficient to recommend appropriate methods of visual screening.

Chapter 10: Cervical cancer screening using visualization techniques.

There is a resurgence of interest in the use of visual techniques to identify cervical intraepithelial neoplasia (CIN). These visual techniques can be divided into two general categories. One is the simple visual screening method, such as direct visual inspection (DVI), during which the cervix is visualized with either the naked eye or a low-power magnification device after the application of a solution of 3% to 5% acetic acid that is used as a chemical contrast agent to highlight regions of CIN. DVI has been evaluated in a number of large clinical trials and is considered by some to be a possible alternative to cervical cytology for primary cervical cancer screening in low-resource settings. The advantages of DVI compared with cervical cytology for these settings are that it is inexpensive, it does not require a laboratory infrastructure, and it provides an immediate result, allowing the use of "screen and treat" protocols. The major disadvantage of DVI is that it is relatively nonspecific and that its sensitivity is low compared with testing for human papillomavirus. The other category of visual techniques includes devices that use electro-optical sensors and light of specific wavelengths produced by lasers or specialized light sources to identify and localize regions of CIN on the cervix. Although these "high-technology" devices are not yet in routine clinical use, several groups and companies have such devices in clinical trials.

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Chlorophyll Fluorescence

Abstract Most strawberry cultivars have flowers that are sensitive to temperatures below 0°C. The development of early or very early cultivars with frost resistant flowers is essential in climates with a danger of spring frosts. Traditionally, breeding programs have used visual screening methods to evaluate the damage to pistils and anthers caused by frost. These methods rely on natural seasonal conditions, are time consuming, and do not provide accurate information on the exact temperature that caused the damage. The objective of this study was to evaluate the use of chlorophyll fluorescence (CF) to estimate the low temperature susceptibility of 64 strawberry cultivars. Strawberry flowers were exposed to continuous low temperatures (0°C for 24 h, 1°C for 24 h, -2°C for 24 h, and finally -3°C for 24 h) and CF was measured following the treatments. Variable fluorescence (Fv) decreased somewhat with time in all genotypes when the flowers were held at -3°C, however, the reduction varied with cultivar. The slight reduction of Fv in the more chilling-tolerant cultivars was not significant, while significant linear or quadratic declines were observed in the more chilling susceptible cultivars. Overall, chlorophyll fluorescence appears to be an effective, simple method for evaluating the low temperature susceptibility of strawberry genotypes.

From basic cell biology to cancer screening

Cdc6p and the members of the minichromosome maintenance (MCM) family of proteins, which associate with the origin-recognition complex (ORC) at initiation of DNA replication, are downregulated and, indeed, absent in quiescent cells. Antibodies recognizing these proteins can therefore be used to detect proliferating cells specifically. In an exciting development, recent research has shown that these observations from basic research can be applied directly to cancer screening.In tissues that normally contain quiescent cells, proliferating cells are characteristic of cancerous and precancerous lesions. However, the visual screening methods frequently used to detect such cells are both time-consuming and difficult to perform accurately as they rely heavily on the identification of subtle differences between cells or of a few abnormal cells among a large population.Antibodies against CDC6 or MCM family proteins therefore have potential applications as a supplement to visual screening for proliferating cells in such tissues by performing antibody staining on the tissue samples. This idea was first tested using antibodies against CDC6 and MCM5 for screening cervical smears and proved very effective1xWilliams, G.H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14932–14937Crossref | PubMed | Scopus (242)See all References1 (Fig. 1Fig. 1). More recently, this antibody-based approach has been applied to detecting neoplastic cells from other systems – for example, bladder, breast and colon2xSee all References2 (Fig. 2Fig. 2). As well as providing a valuable supplement to the visual screening assay, the ability to combine this method with fluorescence detection opens up the possibility of automated screening and quantitation in the future. Such advances could well lead to significant improvements in both the scale and reliability of early-cancer screening programmes.FIGURE 1In the standard histological stain (a) of a cervical smear, abnormal nuclei can be difficult to distinguish against the background cells, whereas, with the horseradish peroxidase (HRP)–antibody-enhanced stain detecting MCM5 (b), abnormal nuclei (brown) are readily seen. For further information, see Ref. 1xWilliams, G.H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14932–14937Crossref | PubMed | Scopus (242)See all ReferencesRef. 1.View Large Image | Download PowerPoint SlideFIGURE 2Frozen sections of normal colon (a) and adenocarcinoma of the colon (b) stained with an antibody against MCM5 followed by fluorescein-conjugated anti-rabbit antibody (green stain), and propidium iodide (red) for all nuclei. For further information, see Ref. 2xSee all ReferencesRef. 2.View Large Image | Download PowerPoint Slide

Cervical cancer prevention using visual screening methods

Although cervical cancer is only the fifth leading cause of cancer deaths in women globally, it remains the leading cause of cancer deaths among women in developing countries. The approach to cervical cancer prevention used in developed countries has failed in most of the world because widespread Pap smear screening and the evaluation by specialists of women who screen positive is expensive and requires an infrastructure that is not easily sustainable in most developing countries. Over the last decade, investigators have explored alternative strategies for cervical cancer prevention that may be easier to implement in developing countries. These include HPV DNA (human papillomavirus DNA) testing, cervicography, and direct visualisation techniques. 1 Of these, direct visual inspection has received the most attention because it is thought to be the least expensive and to have the greatest potential for screening and treatment in one visit. Multiple studies have now evaluated visual screening methods in developing countries. However, presumptions that parameters of effectiveness in controlled research settings can be projected to mass screening programmes may have inherent fallacies. We believe caution is needed when introducing a new approach to screening that could lead to overtreatment of large numbers of women without disease, in efforts to capture and prevent all disease. This paper examines the implications of the expanded use of direct visual inspection (DVI) for screening or diagnosis, raising the difficult question of risks and benefits when treating many to save a few.

Clinically important ocular reactions to systemic drug therapy.

Many systemically administered drugs produce ocular adverse effects. Fortunately, relatively few are capable of causing significant, irreversible visual impairment. It is the responsibility of every clinician when prescribing systemic therapeutic agents to be aware of potential adverse ocular reactions, to appreciate their significance, and to inform the patient of the potential risks of treatment. In instances where serious adverse reactions relate to the cumulative effects of prolonged treatment, it is the responsibility of the prescribing physician to institute appropriate methods of visual screening. In this respect, it is most important to obtain the necessary individual baseline measurements before treatment is commenced. Chloroquine retinopathy is probably the most feared of all adverse ocular reactions to systemic drug therapy. However, it occurs only rarely if the daily dosage of chloroquine does not exceed 250mg. Regular screening using automated perimetry is mandatory if prolonged therapy is contemplated. Amiodarone almost inevitably produces corneal deposits. These rarely produce symptoms, and resolve upon withdrawal of the drug. Optic neuropathy has recently been described with amiodarone. Systemic anticoagulant therapy may be associated with intraocular hemorrhage in patients with pre-existing disciform macular degeneration, and such agents should be used with caution in affected individuals. Systemic corticosteroids produce posterior subcapsular cataracts in susceptible individuals which may profoundly affect visual acuity. Although elevated intraocular pressure may also result from systemic therapy, the relationship between the pressure rise and development of glaucomatous changes remains unclear. Ethambutol may produce optic neuropathy if the daily dosage exceeds 15 mg/kg. The changes are usually reversible within a few weeks of stopping treatment. High doses of tamoxifen may produce a maculopathy with loss of visual acuity, if given for prolonged periods. The risk must be weighed against the benefits of treatment. Patients receiving more than 800 mg/day of thioridazine have developed retinopathy, which is usually reversible if detected early enough. Tricyclic antidepressants and other agents with anticholinergic properties may cause disturbances of accommodation and pupillary dilatation. The latter may rarely precipitate acute angle closure glaucoma in susceptible individuals.

Usefulness of Noise-Field Test as a visual field screening method in human dry dock ( general health ckeck-up system)

Usefulness of Noise-Field Test as a visual field screening method in human dry dock ( general health ckeck-up system)

Costs and methods of preventive visual screening and the relation between esotropia and increasing hypermetropia.

Atkinson has shown that early correction of hypermetropia reduces the incidence of esotropia. If esotropia is reduced by prescribing glasses early, the rate of esotropia-induced amblyopia can be similarly reduced; this would have important economic consequences. We have studied (1) how costs compare to benefits in early visual screening, (2) how videorefraction as used by Atkinson compares to retinoscopy, and (3) whether esotropia is more likely to occur in children who have increasing as opposed to decreasing hypermetropia. The costs of the study so far have been high. It was exceedingly difficult to get all infants invited, come to the clinic and examined. Videorefraction did not compare favourably with retinoscopy in terms of costs and precision, whereas the amount of skill and time needed was approximately equal. The third question, whether esotropia is more likely to occur in children who have increasing as opposed to decreasing hypermetropia, arose from the controversy whether, in the general population, refraction increases or decreases during the first years of life. We found that papers reporting a decrease of hypermetropia in early childhood were studies of large cross-sections of the general population, whereas papers that reported an initial increase originated from ophthalmological practices or strabismus departments. These conflicting results could be reconciled by assuming a population bias: if esotropia is more likely to occur in children with increasing hypermetropia, children with increasing hypermetropia will preferentially be seen by ophthalmologists. It seems natural that children with increasing hypermetropia are more likely to squint, because additional accommodation, needed to overcome increasing hypermetropia, will inevitably confer additional convergence. This relationship has meanwhile been confirmed by others.