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 multi-factorial 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 b-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.3
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 (T1D) involves the progressive autoimmune destruction of insulin producing beta cells in the pancreas. In humans, the manifestation of T1D generally occurs when around 70 per cent of the b-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 b-cell failure and a progressive reduction in insulin secretion (as in T1D) and/or to chronic insulin resistance.5
Glycation 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 a-crystallin 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 sortibol 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 1).10 There has also been correlation between diabetes and the presence of posterior sub-capsular cataracts.11,12 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. Age-related cataract is by far the most common.17
The presentation of congenital cataract is extremely variable, ranging from subtle dot opacities to dense total cataract 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 third are due to genetic conditions, the vast majority of which have an autosomal dominant mode of inheritance and no systemic associations.21 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 part 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.22,24 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 age-related cataracts. These may be genetic. Genetic studies including mapping and mouse cataract models have also linked a number of gene loci and candidate genes to non-syndromic 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.15 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 cataract surgery, 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 C1 form is completed by the clinician. The form includes information such as current and pre-cataract 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 C1 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.
References
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- Negre-Salvayre A, Salvayre R, Auge N, Pamplona R and Portero-Oti M. Hyperglycemia and glycation in diabetic complications. Anitoxidants and Redox signalling, 2009 11(12):3073-3096.
- Yi Lin Y, Sun Z. Current views on type 2 diabetes. Journal of Endocrinology, 2010 204:1-11.
- Nichols J, Cooke A. Overcoming self-destruction in the pancreas. Curr Opin Biotechnol, 2009 20(5):511-5.
- Campbell K. 2009 Fate of the beta-cell in the pathophysiology of type 2 diabetes. Journal of the American Pharmacists Association, 2009 49Sup1:S10-15.
- Kyselova Z, Stefek M, Bauer V. Pharmacological prevention of diabetic cataract. Journal of Diabetes and its Complications, 2004 18(2):129-140
- Asbell PA, Dualan I, Mindel J, Brocks D, Ahmad M, Epstein S. Age-related cataract. Lancet, 2005 365(9459):599-609.
- Kumar PA, Kumar MS, Reddy GB. Effect of glycation on alpha-crystallin structure and chaperone-like function. Biochem J, 2007 408(2):251-8.
- Donaldson PJ, Chee KS, Lim JC, Webb KF. Regulation of lens volume: Implications for lens transparency. Experimental Eye Research, 2009 88(2):144-150.
- Jacob T J. The relationship between cataract, cell swelling and volume regulation. Progress in Retinal and Eye Research 1999 18(2): 223-233.
- Asbell PA, Dualan I, Mindel J, Brocks D, Ahmad M, Epstein S. Age-related cataract. Lancet, 2005 365(9459):599-609.
- Praveen MR, Shah GD, Vasavada AR, Mehta PG, Gilbert C, Bhagat G. A study to explore the risk factors for the early onset of cataract in India. Eye (Lond), 2009 Jun 12.1-9.
- Teitelbaum BA. Reversible 'fingerprint' cataract secondary to diabetes mellitus. Clinical Eye and Vision Care, 1999 10(2):81-84.
- The Royal College of Ophthalmologists. Ophthalmologists commissioning cataract surgery - an outline of good practice, 2004 www.rcophth.ac.uk/docs/publications/published-guidelines/CommissioningCataractSurgery-April2004.pdf
- NHS Choices (2010). www.nhs.uk/choiceintheNHS/Yourchoices/hospitalchoice/Pages/Choosingahospital.aspx
- Association of Optometrists 2004. Department of Health 'Choose & Book' Programme AOP Guidance on Direct Referral of Cataract. www.assoc-optometrists.org/uploaded_files/guidance_on_direct_referral_of_cataract_and_patient_choice per centE2 per cent80 per centA6.pdf
- Hejtmancik JF. Congenital Cataracts and their Molecular Genetics. Semin Cell Dev Biol, 2008 19(2): 134-149.
- Amaya L, Taylor D, Russell-Eggitt I, Nischal KK, Lengyel D. The morphology and natural history of childhood cataracts. Survey of Ophthalmology, 2003 48(2):125-144.
- Yorston D. Surgery for congenital cataract. Community Eye Health, 2004 17(50): 23-25.
- Evans DG. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009 19(4):16.
- Zetterström C, Kugelberg M. Paediatric cataract surgery. Acta Ophthalmol Scand, 2007 85(7):698-710.
- Patterson D. Molecular genetic analysis of Down syndrome. Hum Genet, 2009 126:195-214.
- Sommer CA, Henrique-Silva F. Trisomy 21 and Down syndrome - A short review. Braz J Biol, 2008 68(2): 447-52.
- Akinci A, Oner O, Bozkurt OH, Guven A, Degerliyurt A, Munir K. Refractive errors and strabismus in children with Down syndrome: a controlled study. J Pediatr Ophthalmol Strabismus, 2009 46(2):83-6.
- Creavin AL, Brown RD. Ophthalmic abnormalities in children with Down syndrome. J Pediatr Ophthalmol Strabismus, 2009 46(2):76-82
- Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol, 2004 151(6):657-87.
- Hjerrild BE, Mortensen KH, Gravholt CH. Turner syndrome and clinical treatment. British Medical Bulletin, 2008 86(1):77-93.
- Denniston AK, Butler L. Ophthalmic features of Turner's syndrome. Eye (Lond), 2004 18(7):680-4.
- Francis PJ, Berry V, Moore AT. Bhattacharya S. Lens biology development and human cataractogenesis. Trends in Genetics, 199915(5): 191-6.
- Robman L, Taylor H. External factors in the development of cataract. Eye (Lond), 2005 19(10):1074-82.
? Louise Stainer is an optometrist at Aston University Day Hospital where she is involved in pre- and postoperative care of cataract and refractive surgery patients