Cataract: Part 2 - Systemic diseases and syndromes

Stainer, Louise. The Optician 240.6262 (Jul 23, 2010): 14-17.

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In uncontrolled diabetes, chronic elevation of extracellular glucose occurs due to the cessation of
its control by insulin. Glucose is able to diffuse freely into the lens, as in this particular structure
glucose entry is not conditional on the external insulin activity.

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Headnote
Louise Stainer continues our series about cataract with a discussion of systemic and associated
conditions. Module C14313, one general CET point for optometrists and dispensing opticians
Cataract or opacity of the lens is still the most common cause of blindness. The age-related form
affects over 20 million people worldwide.1 It is a multifactorial trait with both genetic and
environmental components. An association has also been found between cataract and certain
systemic and syndromic conditions. Some of these diseases will be discussed in more detail in this
article.
Diabetes mellitus
Diabetes mellitus is a common metabolic disorder affecting 8 per cent of the world's population.2
It is characterised by abnormally high blood glucose levels or hyperglycaemia. Normally, the
hormone insulin is constantly synthesised by -cells in the pancreas, irrespective of glucose levels
in the blood. It is stored in vacuoles and an elevation of blood glucose levels triggers its release.
Insulin is one of the hormones involved in the regulation of blood glucose; it regulates the uptake
of glucose from the blood into cells including skeletal cells and adipose cells and the conversion of
glucose to glycogen for storage in liver and muscle cells. When blood glucose drops there is a
reduction in the release of insulin and an increase in the secretion of another hormone called
glucagon from the a-cells of the pancreas. Glucagon opposes the action of insulin by stimulating
the conversion of glycogen to glucose.
The hyperglycaemia observed in diabetes mellitus may be a result of a deficiency in insulin
secretion or an impaired response to insulin due to a reduction or absence in downstream
signalling and outcomes following binding of the insulin hormone to its receptor.3
Type 1 diabetes (TlD) involves the progressive autoimmune destruction of insulin producing beta
cells in the pancreas. In humans, the manifestation of TlD generally occurs when around 70 per
cent of the -cell mass has been destroyed and there is insufficient insulin to maintain glucose

homeostasis.4 Subsequently sufferers need to use exogenous insulin administered via different
methods such as injection or pump. Type 2 diabetes (T2D) results from increasing amounts of cell failure and a progressive reduction in insulin secretion (as in TlD) and/or to chronic insulin
resistance. :'
Clycation and lens transparency
In uncontrolled diabetes, chronic elevation of extracellular glucose occurs due to the cessation of
its control by insulin. Glucose is able to diffuse freely into the lens, as in this particular structure
glucose entry is not conditional on the external insulin activity. Therefore conversely during
hyperglycaemia the lens is not able to down-regulate glucose transport.6 Reactions (glycation)
occur between the excess glucose molecules and proteins within the lens such as crystallins
leading to structural alterations. The rate of glycation is increased in hyperglycaemic conditions.6
The modifications of the protein structure of a-crystallin due to glycation have been shown to
compromise its chaperone activity.7 This role normally involves the binding of a-crystallin to other
proteins in the lens to prevent their aggregation after they have been subjected to chemical
modification or heat.8 The chaperone action maintains the transparency of the lens so reduction in
this activity in hyperglycaemic conditions results in lens opacity. Animal and human studies have
shown that the progressive accumulation of glycation pathway end products (advanced end
products of glycation) in the lenses of diabetics contribute to the increased rate
of cataract development (cataractogenesis).6 In addition, the effect of hyperglycaemia on acrystallin function is exacerbated as there is no significant protein turnover in differentiated lens
fibres.7
Diabetes, the sorbitol pathway and sugar cataract
The transparency of the lens is due to the regular orientation of its cellular fibres. The spaces
between the fibres are known as gap junctions. Studies on rat lenses suggest that receptor activity
on peripheral lens fibres and subsequent communication with the rest of the lens via these gap
junctions have a role in the regulation of fibre volume throughout the lens.8 Disruption of the lens
structure due to cellular swelling of the fibres or dilation of the gap junctions increases light scatter
within the lens.
During hyperglycaemia, the increased amounts of glucose entering the lens may also be converted
into sorribol by an enzyme called aldose reductase.6 This pathway is not utilised in this way when
glucose concentrations in the blood are at normal levels. Unlike glucose, sorbitol can not move
across lens fibre cell membranes easily and begins to accumulate. The presence of increased
sorbitol levels results in the disturbance of osmotic homeostasis and swelling of the lens which
may have adverse effects on lens transparency.6 Lens oedema, together with the effects that

glucose has on membrane permeability cause lens stress and culminate in the formation of
a cataract which is often cortical in nature.6,9
Several studies have found an association between diabetes and cortical cataracts (Figure I).10
There has also been correlation between diabetes and the presence of posterior subcapsular cataracts.1112 True acute diabetic cataracts may be bilateral and posterior sub-capsular
nature with delicate feathery like opacities. These cataracts are reversible, regressing when blood
sugar levels return to normal.13 The association between diabetes and certain types
of cataract has been shown to be related to the duration of disease and degree of control. Indeed,
a tendency for diabetics to need cataract surgery at an earlier age than non-diabetics has been
found.11
Obviously, diabetic patients should be encouraged to have regular eye examinations and diabetic
screening. Self-monitoring of blood sugar, a healthy diet and lifestyle and compliance when using
their prescribed treatment regime is important not only to reduce the progression of diabetes but
also secondary complications such as diabetic cataract.
Congenital cataracts
Cataracts can also be defined according to the age at which they begin to develop. Cataract types
include the congenital or infantile cataract which forms within the first year of life, the juvenile
form which presents within the first decade, the presenile form which generally occurs at around
45 years of age and the senile or age-related form the onset of which is later. Agerelated cataract is by far the most common.17
The presentation of congenital cataract is extremely variable, ranging from subtle dot opacities to
dense totalcataract in which all of the lens fibres are opaque.18 There is also a wide range of
causes (Table 1).
Congenital cataracts are mostly idiopathic - their cause is unknown.21 Studies have shown that
approximately one tliird are due to genetic conditions, the vast majority of which have an
autosomal dominant mode of inheritance and no systemic associations.2' However,
congenital cataracts can also be associated with systemic abnormalities, in that the condition
affects the body and not just the eye. Examples include Down's syndrome and Turner syndrome.
Down's syndrome
Individuals with Down's syndrome have all or pan of an extra copy of chromosome 21 in addition
to the normal two copies (trisomy).22 The phenotype or physical characteristic of the condition is
variable. There tends to be a spectrum of intellectual disability ranging from mild to severe.
Down's syndrome is also associated with numerous other clinical traits including congenital heart

disease, an increased risk of childhood leukaemia and early-onset Alzheimer disease.23 Studies
have found numerous ocular associations including strabismus (especially eso-deviations),
nystagmus, refractive errors, most commonly hyperopia, astigmatism and less frequently
congenital cataract.2224 However, total cataracts have been shown to occur in Down's
syndrome.18 Surgery and aggressive management postoperatively is necessary in these cases to
reverse deprivation amblyopia and minimise visual impairment. Other ocular manifestations which
have been shown to occur more frequently in Down's syndrome patients include blepharitis and
glaucoma.25
Turner syndrome
Turner syndrome is a genetic disorder seen in women who have an anomaly of the sex
chromosomes. Normally this involves the complete or partial absence of one of their X (sex)
chromosomes. More rarely, it is due to absence of their Y-chromosome.26 It is one of the most
common chromosomal abnormalities with an incidence of 50 per 100,000 births.26 Individuals
with Turner syndrome have a short stature and are at an increased risk of developing
hypothyroidism and diabetes as well as having congenital malformations of the heart. Although
female sex hormones tend to be present at normal levels during childhood, levels drop to
menopausal levels in adulthood resulting in infertility. Sex hormone therapy (HRT) as well as
growth hormone therapy for growth retardation is generally required.27 Although
congenital cataract is only seen in a small percentage of these patients (less then 5 per cent)
refractive errors are commonly seen (40 per cent) as well as strabismus (33 per cent) and
amblyopia (almost 30 per cent) which needs to be addressed at an early stage to improve the
chances of normal visual development.28
As these articles have illustrated, there are numerous factors associated with congenital and agerelatedcataracts. These may be genetic. Genetic studies including mapping and
mouse cataract models have also linked a number of gene loci and candidate genes to nonsyndromic dominant congenital cataracts. These include mutations in gene coding for the crystallin
proteins within the lens fibres and proteins called connexins that are located within the gap
junctions between len fibres.29
Environmental factors have also been shown to be associated with cataract development. Drugs
such as corticosteroids have been linked to congenital and age-related cataract. Ultraviolet light
and diabetes have been shown to contribute to age-related cataracts. Cataract development has
also been linked to lifestyle (smoking has been linked to age-related cataract).30
Cataract development is by no means straightforward, but further development of genetic
techniques will continue to help researchers to elucidate the underlying mechanisms. In the

meantime, surgical techniques have become more sophisticated enabling an improvement in

quality of life for people with congenital and age-related cataract.
Referral of patients with cataract for surgery
Patients can be referred for treatment of their cataract by their optometrist or general practitioner.
Originally this was to their local NHS ophthalmic unit. However, the government recognised the
problem of long waiting lists and changes made included commissioning agencies also awarding
private providers contracts to undertake elective cataract surgery.14
If the patient is referred for cataract surgery by their general practitioner they are able to choose
the hospital that they are referred to. Since April 2009 it is their legal right to select any hospital
offering a suitable treatment that meets NHS standards and costs.1"1 However, if the patient is
not comfortable making this decision, it can be decided by the general practitioner.
If the patient's appointment with their optometrist or general practitioner indicates that they
need cataractsurgery, they may find it helpful to have written information regarding the procedure
to consider in their own time following a general discussion during their appointment. The patient
may be happy to proceed with the referral for surgery immediately. Alternatively they may want
time to think about it, research it further and maybe discuss it with family members. The patient
then needs to contact the clinician or vice-versa with their discussion.
Since January 2005, optometrists refer their cataract patients using the Choose and Book referral
scheme, meaning that the patient is given the choice of a number of local providers for
their cataract surgery. If they decide to proceed with the referral for surgery the Cl form is
completed by the clinician. The form includes information such as current and precataract prescription and cataract type and includes a box in which the optometrist can enter any
further relevant information. The remuneration that the optometrist receives for the referral and
patient assessment varies across the country.16 The patient completes and signs the reverse of
the form, consenting to the referral and the transmission of their personal information to the
provider. Usually the clinician faxes the Cl form to the chosen provider. At our facility on reception
of the form we telephone the patient promptly to arrange a pre-operative assessment. The patient
is informed about what the appointment involves and advised that it is better for them to be
accompanied by a friend or family member as their pupils will be dilated. If the individual is
suitable for surgery at our site (we are a day hospital and the surgery is performed under local
anaesthetic) they are given a date for surgery and information regarding the procedure. They are
also able to telephone us should any further questions arise.

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