The objectives of epidemiology in understanding and managing disease processes
determine the burden of congenital cataract and cataract related blindness/visual impairment
study the natural history
identify the underlying causes/aetiological factors, including the causes of associated visual impairment/blindness
inform the development of, and evaluate, preventive and therapeutic measures from the level of the individual to population based policies
Whilst most clinicians are familiar with classical observational and interventional epidemiology, the field has evolved to include fields such as lifecourse epidemiology, genetic epidemiology and health services research:
lifecourse epidemiology – the study of physical and social hazards during gestation and childhood (and later life) that affect disease risk and health outcomes in later life. It aims to ‘identify the underlying biological, behavioural and psychosocial processes that operate across the life span’ 
genetic epidemiology – the study of the interactions between genetic and environmental determinants of disease and health outcomes
health services research – the study of the accessibility, quality, and cost-effectiveness of health care services, with a focus on patient experiences and reported outcomes
2.1.1 Methodological Challenges to Epidemiological Research in Congenital Cataract
The challenges include limiting misclassification bias, selection bias and confounding, and lack of statistical power to determine the role of chance. These are of particular importance when undertaking research into a ‘rare’ disorder (one with a prevalence of less than 5 in 10,000 of the population). The greatest challenge of any study into a rare disease is the creation of a study population which is representative of the total population at risk.
When a disease is uncommon, it can be a challenge to obtain a sufficiently large sample size. Studies with small numbers of children are prone to chance findings (i.e. false positive findings or type I error). Small sample sizes may also result in failure to achieve statistical significance for even potentially large effects (i.e. false negative findings, or type II errors).
Selection Bias: Misclassification and Varying Definitions of Disorders and Outcomes
The misclassification of non-diseased/non-affected individuals as diseased/affected (or vice versa) has a profound effect on the subsequent analysis.
The differing definitions of congenital cataract include:
Any lens opacity present at birth
Any lens opacity newly diagnosed in the first year of age, particularly if associated with another structural ocular anomaly or congenital systemic disorder (also known as ‘congenital/infantile cataract’). This definition is the most robust, on the basis that unless the examination occurred at birth it is difficult to exclude a congenital onset of lens opacity.
As well as the example of the differing definitions of congenital cataract, associated or secondary conditions such as microphthalmia, or glaucoma following cataract surgery have been defined in numerous ways in the existing literature.
Selection Bias Heterogeneity of Study Populations
Children with congenital and infantile cataract form a varied group, and the populations investigated within the literature reflect this heterogeneity and compounds the problems of non-standard case definition. The resultant case mix adversely impacts on attempts to compare the findings of different studies and on the generalisablity of individual study findings. Additionally, risk factor profiles for the development of different outcomes may not be appropriately dealt with at analysis.
Investigations of potential associations must also consider the issue of confounding. The challenge is to determine the independent effect of one variable on the risk of a particular outcome once other variables have been taken into account, as well as the direction and size of effect one variable has on another variable’s association with the risk of the outcome.
The hierarchy of evidence (reflecting the hierarchy of study methodology) can be used to consider the strength of the evidence from epidemiological research into congenital cataract. Methods used in the study types at the “top” of the hierarchy are more likely to minimise bias and confounding (Table 2.1). But, most importantly, methodology needs to be both appropriate to the research question and ethical. For example, to investigate a risk factor for disease, a cohort or case control approach would be adopted rather than an interventional trial exposing individuals to the risk factor.
Levels of evidence 
Level of evidence
1 (highest level)
Systematic review of inception cohort studies
Systematic review of randomised trials
Rare treatment harms
Systematic review of case control studies or studies revealing dramatic effects
Inception cohort study
Randomised trial or observational study with dramatic effect
Systematic review of nested case control or dramatic effect
Rare treatment harms
Randomised trial or observational study with dramatic effect
Cohort or control arm of randomised trial
Non randomised controlled cohort / follow up study
Systematic review of case-series
Systematic review of case-control studies, historically controlled studies
Case-control studies, historically controlled studies
5 (lowest level)
Opinion without explicit critical appraisal, based on limited/undocumented experience, or
based on mechanisms
Thus, the hierarchy is not an inflexible construct, as a ‘higher’ category of study methodology does not guarantee study quality. For example, a poorly conducted randomised trial will be less robust than a well conducted cohort study with multivariable analysis to account for confounding.
2.2 The Burden of Congenital Cataract
Despite being an uncommon condition, congenital and infantile cataract remains a significant cause of childhood visual impairment worldwide and one of the most common causes of preventable childhood severe visual impairment or blindness . Its prominence relative to the many other conditions which impact on children’s eyes and vision is explained by a combination of factors. Firstly, limited understanding of aetiology for a significant proportion hampers prevention, and presently there is no effective treatment for cataract due to monogenetic disease other than genetic counselling. Secondly, there are obstacles to prompt and effective management for affected children in resource poor settings. Thirdly, there has been a greater success in reducing the impact of the other causes of childhood blindness, for example corneal opacity disorders caused by measles and or vitamin A deficiency.
Determination of the true global burden of congenital/infantile cataract, particularly in the context of the limited health care infrastructure common to lower and middle income settings, is made difficult by the methodological challenges of population based research on rare conditions. Investigations of the country specific prevalence of paediatric disorders tend to derive estimates using the denominator of school groups or health centres rather than whole populations, as the latter are less easily accessible for research purposes. This leads to under representation of children from groups existing outside formal health care or administrative structures. These are also the children most vulnerable to adverse outcomes from health and developmental disorders, leading to both under representation of blindness/visual impairment due to cataract, and selection bias within investigations of outcome.
2.2.1 Prevalence and Incidence
The prevalence of a disorder is the proportion of a defined population affected by the disorder at any time point, whereas the incidence is the number of new cases (‘incident cases’) added to the existing pool over a defined time period. The cumulative incidence, also described as the cumulative risk, is the incidence rate (or risk of diagnosis for the individual) over a specified period of time, which may be the whole lifetime of the individual. For example the childhood cumulative incidence or risk of cataract would be the rate of diagnosis of new paediatric cases within a defined population, equating to the risk of being diagnosed with cataract by 18 years of age.
Ascertaining Incident Cases
Reports from newborn screening programmes or national anomaly registers in industrialised settings can provide some information on the frequency of occurrence of a congenital disorder such as cataract. A North American study, using a national non-statutory birth anomaly reporting system to ascertain cases, estimated the incidence of disease at 2.03 per 10,000 births  whilst the discharge diagnoses entered into Denmark’s statutory National Register of Patients (NRP) were used to estimate the cumulative incidence amongst Danish children at 5.2 per 10,000 by 16 years old . Another more recent European study involving the non-statutory Swedish National Cataract Register, established in 2006 with an aim to standardize management and improve outcomes, reported an incidence of significant cataract (defined as ‘cataract requiring surgery’) of 1.9 per 10,000 live births . However non statutory systems are by their nature open to under ascertainment of cases, and even systems which compel reporting have been found to under report the number of children with congenital cataract . A British population based study using active surveillance, an approach which has been shown to have a higher case ascertainment than the formal statutory clinical reporting process [28, 36] estimated the incidence of cataract in the first year of life at 2.5 per 10,000 (95 % confidence interval 2.1–2.9), with a cumulative incidence of congenital and infantile cataract in the first 5 years of life of 4 per 10,000 . Active surveillance is the monitoring of an entire population at risk , in which there is not only the identification of cases but also confirmation of the absence of cases, thus providing a more precise estimation of frequency.
In 1997 it was estimated that the number of children across the world born each year with congenital cataract was 20–40,000, with a worldwide prevalence of between 1 and 4 affected children per 10,000  The proportion of affected children may be as high as 1.5 per 1000 in low-income countries with high under five mortality rates. In high-income countries with lower under five mortality rates, however, the prevalence is around 0.3 per 1000 children . The estimates of prevalence and incidence of congenital and infantile cataract are sensitive to the overall health and survival of the paediatric population, the socio-economic developmental status of the region as well as the existing organisation in place for the detection of early life vision and eye disorders.
2.2.2 The Burden of Congenital Cataract Blindness
Childhood visual impairment (vision in the better eye worse than 0.48 logMAR or 6/18 Snellen according to World Health Organisation taxonomy), severe visual impairment (vision worse than 1.0 or 6/60) and blindness (worse than 1.3 or 3/60) impact on society as well as the individual through the cost of medical and social support for the child and the adult she becomes, as well as the loss of potential employment related income. It has been estimated that over 21 % of the world’s blind children owe their impairment to cataract, with lens related disease coming second to retinal disorders as the most common cause of blindness . The wide range in the proportion of ‘blind school’ students with cataract (Fig. 2.2) reflects the variation in the frequency and causes of visual impairment across the world. In 1997, the global estimate was 15 % , but the relative importance of childhood cataract as a cause of blindness has grown as the pattern of the causes of childhood blindness has changed, with, in particular, successes in the programmes of vitamin A supplementation and measles immunization in reducing the impact of childhood corneal opacity [7, 17, 38]. Whilst we lack the contemporaneous data needed to definitively state the true proportion of childhood cataract related blindness, it is reasonable to assume that congenital and infantile cataract is one of the most common causes of preventable childhood visual impairment in many settings .
2.3 Natural History
Congenital and infantile cataract can lead to a lifelong burden of blindness if
visually significant opacity is untreated
there is a delay in treatment
there is failure to institute effective post operative visual rehabilitation to address sensory deprivation amblyopia
there are co-existent ocular or systemic disorders capable of causing impairment
iatrogenic conditions such as secondary glaucoma (of which there is a life-long risk) develop following surgery.
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