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Cataract
Article in Nature Reviews Disease Primers · June 2015

DOI: 10.1038/nrdp.2015.14
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PRIMER
Cataract
Dennis Lam1,2, Srinivas K. Rao3, Vineet Ratra2, Yizhi Liu1, Paul Mitchell4, Jonathan King5,
Marie-José Tassignon6, Jost Jonas7, Chi P. Pang8 and David F. Chang9
Abstract | Cataract is the leading cause of reversible blindness and visual impairment globally. Blindness
from cataract is more common in populations with low socioeconomic status and in developing countries
than in developed countries. The only treatment for cataract is surgery. Phacoemulsification is the gold
standard for cataract surgery in the developed world, whereas manual small incision cataract surgery is
used frequently in developing countries. In general, the outcomes of surgery are good and complications,
such as endophthalmitis, often can be prevented or have good ouctomes if properly managed.
Femtosecond laser-assisted cataract surgery, an advanced technology, can automate several steps; initial
data show no superiority of this approach over current techniques, but the results of many large clinical
trials are pending. The greatest challenge remains the growing ‘backlog’ of patients with cataract blindness
in the developing world because of lack of access to affordable surgery. Efforts aimed at training additional
cataract surgeons in these countries do not keep pace with the increasing demand associated with ageing
population demographics. In the absence of strategies that can prevent or delay cataract formation, it is
important to focus efforts and resources on developing models for efficient delivery of cataract surgical
services in underserved regions. For an illustrated summary of this Primer, visit: http://go.nature.com/eQkKll
The crystalline lens is a transparent, biconvex struc- more than 13 million cataract surgeries were performed
ture in the human eye that functions in a similar way globally in 2013 (REFS 1,2). Simultaneous correction of
to the lens of a camera. A cataract is a lens abnormality refractive errors, such as astigmatism (blurred vision
characterized by decreased transparency and increased mainly due to uneven curvatures of the cornea) and
cloudiness. Cataract is the leading cause of reversible vis- presbyopia (age-related defect in focus on near objects),
ual impairment and blindness globally 1. The condition is reduces the need for glasses and is now an important
most prevalent in populations with lower socioeconomic consideration of modern cataract surgery.
status and developing countries. Various risk factors can complicate cataract surgery,
Crystallins are the main proteins making up the lens leading, for example, to a small pupil or to rupture of the
and the lens surfaces, and are responsible for their refrac- posterior capsule during surgery. However, if properly
tive function. Modification, aggregation and precipita- managed, most complications are still compatible with
tion of crystallins are the main mechanisms underlying good visual outcomes. Endophthalmitis (an inflamma-
cataract development. So far, no method that can prevent tory condition of the intraocular cavities usually caused
this process has been found. Most cataracts are caused by infection)3 is the most serious sight-threatening com-
by age-related degeneration; however, cataract can plication, but its incidence is low and might be declining
also develop secondary to trauma or as a consequence with increased use of intracameral antibiotics injected
of another disease. Cataract rarely occurs in children into the anterior chamber of the eye during surgery.
Correspondence to D.L. (see BOX 1 for an overview of the types of cataract). The success and functional outcomes of cataract sur-
e-mail: dlam.sklo.sysu.cn@
The only treatment for cataract is surgical removal gery have been greatly enhanced by advances in surgical
gmail.com
State Key Laboratory of
of the lens and replacement with a permanent artifi procedures, training and technology. Femtosecond laser-
Ophthalmology, and cial intraocular lens (IOL). Successful cataract sur- assisted cataract surgery (FLACS)4 is able to automate
Zhongshan Ophthalmic gery universally improves vision and quality of life. several steps of the procedure. However, this techno
Center, Sun Yat-Sen Phacoemulsification (ultrasonic emulsification of the logy adds substantial cost, and significant differences in
University, 54 South Xianlie
Road, Guangzhou 510060,
lens contents, also known as phaco) is the gold standard visual outcomes or complication rates compared with
China. for cataract surgery in the developed world. By contrast, phacoemulsification have yet to be proven. IOL techno
manual small incision cataract surgery (M‑SICS) with a logy continues to improve and is the focus of much
Article number: 15014
doi:10.1038/nrdp.2015.14
self-sealing and sutureless incision is commonly used in research and development. Much of this innovation is
Published online low- and middle-income countries. Both phacoemulsi directed at reducing the patient’s need to wear glasses.
11 June 2015 fication and M‑SICS achieve excellent visual results; To enable increased precision in the selection of these
NATURE REVIEWS | DISEASE PRIMERS VOLUME 1 | 2015 | 1
© 2015 Macmillan Publishers Limited. All rights reserved

PRIMER
Author addresses
surgeons do not keep pace with the changing popula-
tion demographics and increasing rates of age-related
1
State Key Laboratory of Ophthalmology, and Zhongshan Ophthalmic Center, cataract. As no methods to prevent or delay cataract
Sun Yat-Sen University, 54 South Xianlie Road, Guangzhou 510060, China. development are currently available, greater attention is
2
C‑MER (Shenzhen), Dennis Lam Eye Hospital, Shenzhen, China. needed to guarantee effective delivery of cataract sur-
3
Darshan Eye Clinic, Chennai, India.
gery in underserved regions. In this Primer, we discuss
4
Department of Ophthalmology, Centre for Vision Research, Westmead Hospital,
University of Sydney, Sydney, Australia.
the epidemiology, mechanisms, pathophysiology and
5
Department of Biology, Massachusetts Institute of Technology, Cambridge, molecular genetics of cataract. We consider strategies to
Massachusetts, USA. address cost-effectiveness and quality of life and give an
6
Department of Ophthalmology, Antwerp University Hospital, Brussels, Belgium. outlook of future developments in cataract prevention
7
Department of Ophthalmology, Ruprecht-Karls-University, Heidelberg, Germany. and management.
8
Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong,
Hong Kong, China. Epidemiology
9
Department of Ophthalmology, University of California, San Francisco, California, USA. According to the 2010 Global Burden of Disease Study 2
and other worldwide meta-analyses7,8, 32.4 million
‘premium’ IOLs, methods have been developed to accu- individuals worldwide were blind (visual acuity <3/60;
rately measure the biometric parameters of the cata- with 60/60 representing normal vision) and 191 million
ractous eye using optical interferometry. This method individuals were visually impaired (visual acuity <20/60
is more accurate than the traditionally used ultrasound but ≥3/60) in 2010. Globally, the leading overall cause of
biometry 5. Furthermore, the formulae to calculate the blindness was cataract, followed by uncorrected refrac-
IOL power have improved, which ensure that the final tive error; uncorrected refractive error was the leading
refractive outcome of cataract surgery is excellent 6. global cause of moderate to severe visual impairment,
As exciting as these technologies are, the greatest followed by cataract. This frequency-based ranking did
challenge remains the growing prevalence and ‘back- not change between 1990 and 2010. However, large dif-
log’ of patients with cataract blindness in the develop- ferences in the causes of blindness were apparent when
ing world. In these countries, there is a lack of access to analysed according to region. In 2010, the percentage of
affordable surgery, and efforts aimed at training cataract blindness caused by cataract ranged from <15% in high
socioeconomic regions to >40% in south and southeast
Asia and Oceania9,10. As with blindness, the percent-
Box 1 | Main types of cataract age of moderate to severe visual impairment caused by
cataract was smallest in higher socioeconomic regions
Age-related cataract (13.0–13.8%) and largest in south and southeast Asia
• Most common form of cataract (both >20%) (FIG. 1). Across all regions, women had a
• Usually develops in individuals >50 years of age larger percentage of blindness (35.5% versus 30.1%) and
Childhood cataracts moderate to severe visual impairment (20.2% versus
• Congenital (present at birth) 15.9%) caused by cataract than did men.
• Juvenile (develops after birth)
Risk factors
• Usually caused by genetic conditions, congenital
disorders or intrauterine infections Adult-onset cataract is primarily age related11. In fact,
the most important factor associated with cataract is age;
Secondary cataract almost everyone living long enough will develop cata-
• After trauma or surgery of the eye ract 12. Development of cataract is accelerated by meta-
• Caused by other eye disease (for example, glaucoma bolic conditions such as diabetes mellitus13. Diabetic
or infection of the eye) individuals develop cataracts approximately 20 years
• Caused by certain drugs (for example, corticosteroids) earlier and undergo cataract surgery for visually signifi-
or radiation exposuer cant cataracts at a much younger age than people with-
• Associated with systemic diseases (for example, out diabetes13,14. Other metabolic conditions that cause
diabetes mellitus) cataract include hypocalcaemia, Wilson disease and
Morphological classification myotonic dystrophy 15. There is an increased incidence
• Subcapsular (see illustration, left) of cataract in patients with pseudo-exfoliation syndrome
• Nuclear (see illustration, middle) and atopic dermatitis16,17. Ischaemic ocular conditions
• Cortical (see illustration, right) such as pulseless disease, thromboangiitis obliterans and
anterior segment necrosis also lead to cataract 11.
Other causes for cataracts include systemic, topical
or inhaled corticosteroid use. Corticosteroids lead to
cataract in a dose- and duration-dependent manner 18.
Other drugs associated with cataract are pheno
thiazines, miotics, amiodarone and statins19. Along
with blunt trauma and perforating injuries, ionizing
radiation, infrared radiation (to which glassblowers are
frequently exposed) and microwave radiation can also
Nature Reviews | Disease Primers
2 | 2015 | VOLUME 1 www.nature.com/nrdp

PRIMER
0.96–1.05%
1.05–1.10%
1.10–1.85%
Not applicable
Data not available
Nature Reviews | Disease Primers
Figure 1 | Global prevalence of visual impairment due to cataract. The lack of accessibility to health care and limited
financial resources become prohibitive factors for patients with cataracts in developing countries, which results in more
blindness due to cataract, especially in southeast Asia and Africa. Data show the prevalence of cataract in visually
impaired populations. Reprinted from REF. 173 copyright (2010) World Health Organization.
cause cataract 20–22. Alkali burns are more likely lead to of the most common causes of visual impairment after
cataract than acid injuries23. Ocular conditions caus- surgery 29. This condition is caused by clouding of the
ing cataract are uveitis, retinitis pigmentosa, essential remaining lens capsule, but can be easily treated by a
iris atrophy, chronic hypotony, absolute glaucoma and YAG (yttrium aluminium garnet)-laser capsulotomy.
high myopia14. Cataract also occurs secondary to intra
ocular surgeries — glaucoma filtration surgery and vit- Mechanisms/pathophysiology
rectomy 15. Furthermore, epidemiological studies24 have The human crystalline lens is an encapsulated bag of
demonstrated that lower socioeconomic status, lower transparent sequestered proteins. Changes in the arrange-
education level and poorer overall nutrition are associ- ment and alterations in the character of the lens proteins
ated with increased prevalence of age-related cataracts. result first in increasing rigidity of the lens, and eventual
Exposure to sunlight and ultraviolet B (UVB) radiation loss of transparency 30. The first process causes presbyopia
accelerate cataract development 25,26, as do smoking and — the loss of natural focusing ability (accommodation).
alcohol consumption27. Congenital or juvenile cataracts The second process leads to cataract (FIG. 2).
are rare compared with age-related cataract; they can be
idiopathic; inherited (autosomal dominant, recessive or Changes in lens proteins
X‑linked); caused by intrauterine infections with rubella, Crystallin biology. The lens is a unique organ that lacks
varicella, toxoplasmosis or herpes simplex; or associated arterial or venous blood circulation and exhibits rela-
with various systemic disorders (such as galactosaemia) tively low levels of cellular metabolism. The elongated
or genetic syndromes (such as trisomy 21)15. lens fibre cells lack organelles such as nuclei, mitochon-
dria and ribosomes, and are packed with a high concen-
Surgical rate tration of distinctive proteins — the lens crystallins31.
Cataract surgery is performed more often in developed The crystallins are transparent and have a high refractive
regions, including North America, western Europe and index. The lens proteins are not replaced or degraded,
Japan, with 4,000–6,000 surgeries compared with ≤500 and the continued transparency of the lens depends
surgeries per 1 million people in developing regions, on crystallins maintaining their native structures and
such as sub-Saharan Africa 28. Exceptions to these solubility throughout the human lifetime. Loss of their
trends include India, which boasts high surgery rates, native fold renders crystallins prone to aggregation into
and China, which has few surgeries relative to its gross high molecular-weight complexes, which results in cata-
national product. Secondary cataract after cataract sur- ract32. In juvenile cataract, aggregation is often caused by
gery (with or without implantation of an IOL) is one mutations in the genes encoding lens proteins33.

PRIMER
Lens fibre cells are packed with two families of pro- polypeptides chains in the aggregated state36,37. A frac-
teins, the β- and γ‑crystallins; α‑crystallins are chaper tion of the cataractous material is insoluble and probably
ones that suppress protein aggregation 34 (TABLE 1) . represents covalently linked protein chains.
At concentrations of 200 mg/ml, crystallins comprise Advances in mass spectrometry have enabled the
~90% of the total cellular proteins of the lens34. The characterization of amino acid modifications in the
β- and γ‑crystallin families exhibit duplicated domains aggregated protein chains in cataract. Covalent modifi-
with respect to amino acid sequence and conformation. cations are common, including deamidation, oxidation,
Each domain exhibits a double Greek key β‑sheet fold. glycation and truncation36,37. Crystallin deamidation is
The closely related members of the γ‑family, γC-, γD- particularly common36–38. This introduces a negative
and γS‑crystallins, are stable monomers. β‑crystallin charge into the protein from conversion of glutamine
family proteins, including βA- and βB‑crystallin, are residues to glutamates. In a similar reaction, deamidation
homologous to the γ‑family members and to each other, of asparagine yields aspartates39. Deamidation lowers the
but form oligomers. The α‑crystallin chaperones form a thermodynamic stability of βA3- and βB1‑crystallins,
soccer-ball-like complex of many αA and αβ subunits35. leading to increased propensity to aggregate compared
The expression of closely related but slightly divergent to the wild-type proteins40–42. Similarly, deamidation of
proteins is thought to provide a mechanism for inhibit- glutamines on interacting domains destabilizes human
ing crystallization of the concentrated crystallin proteins γD-crystallin43.
in the lens35. Some amino acids are particularly sensitive to oxi-
dation, including cysteine, methionine and tryptophan,
Crystallin alterations. In a cataractous lens, crystallins and oxidation of these residues has been identified at
are tightly associated in high molecular-weight aggre- numerous sites in protein chains recovered from cata-
gates or polymers, and the formation of these complexes ract37. In aged cataracts, cysteines are more susceptible to
accounts for changes in light scattering and opacity. oxidation at some positions than at others37. Oxidation
Crystallin aggregates require strong denaturants for of tryptophan opens the indole ring and reduces aroma
solubilization, such as sodium dodecyl sulphate (SDS), ticity, which would be expected to destabilize the native
urea or guanidinium hydrochloride, and as a result conformation. Indeed, oxidation of tryptophans is
little is known about the conformation of the crystallin increased in cataractous lenses at several sites34. The
Posterior
Ciliary body capsule
Iris
Cortex
Anterior
Vitreous
Lens chamber
humour
Cornea Nucleus
Zonules
Anterior
capsule
Old age,
Covalent inadequate
modification and damage repair and domain
swapping
Suppression
of aggregation
Partially
Crystallin in folded unfolded Crystallin aggregates
conformation α-crystallin crystallin (conformation
(clear) (chaperone) unknown, opaque)
Cataract development
Figure 2 | A model for the pathogenesis of adult-onset cataract. Crystallins in the human lens can |be
Nature Reviews damaged
Disease Primers
or modified by various factors (such as ultraviolet light, oxidation and free radicals). This damage leads to partial
unfolding of the proteins. If the damaged proteins fail to refold or to be sequestered by lens chaperones, they
aggregate and ultimately form a cataract.

PRIMER
Table 1 | Crystallin genes and proteins expressed in the human lens from the fully denatured state45. Aggregation competing
with in vitro refolding has been systematically studied
Protein Size (Da) Residues Gene Chromosomal location for human γD‑crystallin, one of the major γ‑crystallins
αA 19,909 173 CRYAA 21q22.3 in the lens nucleus46. During refolding, γD‑crystallin
αB 20,159 175 CRYAB 11q23.1 exists as a partially folded precursor with a native-like
carboxy‑terminal domain and an incompletely folded
βA1 23,191 198 CRYBA1 17q11.2
amino‑terminal domain47. The C‑terminal domain con-
βA2* 21,964 196 CRYBA2 2q35 tains the most aggregation-prone regions. As expected,
βA3 25,150 215 CRYBA1 ‡
17q11.2 these aggregation reactions are efficiently supressed by
βA4 22,243 195 CRYBA4 22q12.1 incubation with α-crystallin48. βA3‑crystallin exhibits
a related in vitro aggregation reaction, which can be
βB1 27,892 251 CRYBB1 22q12.1 suppressed by βB1‑crystallin49.
βB2 23,249 204 CRYBB2 22q11.23 Although the chain conformation in aggregates
βB3 24,230 211 CRYBB3 22q11.23 remains to be determined, molecular dynamics cal-
culations suggest domain-swapping interactions
γC 20,747 173 CRYGC 2q33.3
between partially unfolded crystallin chains50 (FIG. 2).
γD 20,607 173 CRYGD 2q33.3 Because γ- and β‑crystallins have two homologous
γS 20,875 177 CRYGS 3q27.3 domains, domain swapping could propagate into a
Based on data from REF. 32. CRYA, crystallin, alpha; CRYB, crystallin, beta; CRYG, crystallin, large polymeric structure. Aggregation is suppressed
gamma. *No protein detected in lenses of neonates. ‡βA3‑crystallin is translated from an when α‑crystallin is available, but this function might
initiation codon upstream from that of βA1. be lost in older adults. In age-related cataract, crystal-
lin stability is lost, which predisposes the proteins to
partially or fully unfold. In adults with wild-type alleles
four conserved tryptophans of the γ‑crystallins are all at the crystallin locus, protein damage is presumably
buried in the hydrophobic core of the protein; their caused by external agents, such as UV radiation, heavy
oxidation to less-aromatic side chains destabilizes the metals and lens toxins51. Given the oxidative nature of
native conformation44. much of the damage reported, crystallins are probably
The aggregated protein fractions from cataractous directly affected, but metabolic systems that maintain
lenses also contain truncated crystallin polypeptide the redox and ionic environments in the lens might
chains and peptide segments. Truncations can result in also be involved52. As discussed above, UV radiation is
substantial protein destabilization and increased pro- associated with cataract formation25. Most of the UV
pensity for aggregation40. Peptides isolated from cata- radiation is absorbed by the cornea, but UVA and the
ractous lenses also inhibit the chaperone function of longest wavelengths of UVB radiation are absorbed by
α-crystallin41. the lens53, which has been shown to damage lens pro-
teins in vitro and in animal models53,54. UV filters such
Cataractogenesis as 3‑hydroxykynurenine can protect lens proteins55,
As the conformation of crystallin aggregates remains and the crystallins themselves can efficiently disperse
unknown, it was often assumed that aggregates are not absorbed energy 56. In guinea pigs, UV radiation is
the product of repeating protein interactions. However, responsible for a range of deleterious effects on the lens,
the interactions are likely specific and repeating — for including loss of water-soluble proteins, formation of
example, domain-swapping or loop and sheet inser- disulfide bonds and alteration of the cy toskeleton
tions42. Although amyloid fibrils do not represent the and membranes57.
bulk of the aggregated protein, some role for this form In hereditary cataract, a number of crystallin muta-
cannot be ruled out 38. Further structural studies are tions are associated with altered solubility and crystal-
required to determine polypeptide chain conformations lization propensity without substantial destabilization of
and contacts in cataract aggregates. the mutant subunits47. However, in hereditary cataract,
An important difference between aggregates in cata- aggregates contain not only mutant crystallin but also
ract compared with those in other protein deposition wild-type protein.
diseases is the absence of clearly defined microscopic
morphology. Although textured cytoplasm with a rough Molecular genetics of cataract
appearance was reported in an animal model with oxida- Both congenital and age-related cataracts are affected
tive damage of the lens that led to aggregates and light by heritability. Congenital cataracts mostly follow
scattering 43, this finding does not correspond with the Mendelian autosomal dominant, autosomal recessive
intracellular aggregates observed in diseases such as and X‑linked inheritance patterns, with more than 50
Alzheimer, Parkinson and Huntington disease. Similarly, genes identified58. Approximately half of non-syndromic
electron microscopy of cataractous lenses from a rat congenital cataracts are caused by mutations in crystallin
strain with increased oxidative stress revealed highly genes and ~15% by connexin mutations. Mutations
textured globular and fibrillar patterns44. in genes encoding transcription factors, including
Under physiological conditions and in their native FOXE3 (forkhead box protein E3), PITX3 (pituitary
state, the crystallins are highly soluble and do not aggre- homeobox 3), HSF4 (heat shock factor protein 4), MAF
gate. These γ- and β‑crystallins can be refolded in vitro (transcription factor MAF), PAX6 (paired box protein

PRIMER
PAX6) and NHS (Nance–Horan syndrome protein), the lacrimal apparatus, eye alignment in the orbita,
can also cause cataract. The diversity of identified genes motility and pupillary function is helpful for planning
reflects the heterogeneous mechanisms and phenotypic surgery and providing a prognosis of the patient’s vis-
variations evident in cataract heritability. ual function. Slit lamp biomicroscopy is performed to
Notably, at least two congenital cataract genes, HSF4 examine the eyelids, lashes, cornea, anterior chamber,
(REF. 59) and EPHA2 (REF. 60) (encoding ephrin type‑A pupillary dilatation and hardness of cataract. Detailed
receptor 2), also contribute to the development of age- fundus examination through a dilated pupil can evalu-
related cataracts through interactions with environ ate the status of the lens, macula, peripheral retina, optic
mental factors. Genotypic differences exist among nerve and vitreous humour 69. Examination of the red
cataract subtypes: for example, the frequency of two fundal reflex (the reddish-orange reflection of light from
mutated alleles in SOD1 (superoxide dismutase 1) dif- the retina) using a direct opthalmoscope lens set at +10
fer between patients with cortical cataract and patients dioptres, at a distance of 60 cm, will enhance the areas
with either nuclear or posterior subcapsular cataract 61. producing optical aberrations and thus help to diagnose
Similar differences were found in the frequency of muta- cataract. Supplement tests — for example, for contrast
tions in OGG1 (N‑glycosylase/DNA lyase)62. GSTM1 sensitivity, glare disability and ocular wavefront testing
(glutathione S‑transferase mu 1) mutations increase risk for visual aberrations — can help to identify the cause
for cortical age-related cataract 63. In a Chinese study 64, and level of severity of visual symptoms70. Testing using
one single-nucleotide polymorphism in WRN (Werner a potential acuity meter, laser interferometer or scanning
syndrome ATP-dependent helicase) was associated with laser ophthalmoscope projects an image onto the retina
age-related cataract in general and another one with cor- through relatively clear regions of the lens and attempts
tical cataract specifically, and a BLM (Bloom syndrome to predict the visual acuity following cataract surgery 71.
protein) polymorphism with nuclear cataract. Genetic If necessary, other ancillary tests are performed, includ-
diagnosis of heritable cataract has become increasing colour vision or visual field measurement, optical
ingly reliable with recent technological advances. Next- coherence tomography, fluorescein angiography and
generation sequencing has identified cataract-causing B‑scan ultrasonography.
gene variants in 27 of 36 patients (75%)65. In exome
sequencing of 18 Chinese families, 12 of them (67.6%) Prevention
showed cataract mutations in 34 genes66. A recent meta- As mentioned above, age-related cataract is a multi
analysis of genome-wide association studies has con- factorial disease, and genetic and environmental fac-
firmed the association of polymorphisms in KCNAB1 tors contribute to cataract development 12, including
(voltage-gated potassium channel subunit beta‑1) and nutrition72. Epidemiological research suggests that the
CRYAA (αA‑crystallin) with age-related nuclear cataract risk of cataract can be diminished by adhering to diets
in Asians67. New technologies will enable exhaustive that contain high levels of vitamin C, lutein, zeaxanthin,
mapping of cataract genes, and the characterization of B vitamins, omega‑3 fatty acids and multivitamins and
gene functions should lead to a complete understand- avoiding frequent and large intakes of simple carbo
ing of cataractogenesis and enable the identification of hydrates73. In the Age-Related Eye Disease Study, intake
genetic markers to aid prevention. of a multivitamin supplement was moderately protec-
tive against the development of cataracts74. However,
Diagnosis, screening and prevention because cataract is a degenerative disease mainly caused
Diagnosis by ageing, methods of prevention are scarce.
Cataracts are visible during clinical evaluation of the eye
(FIG. 3). Patients are evaluated for visual impairment and Management
other symptoms, and for concomitant eye diseases that Deteriorating visual function because of cataract
could influence the surgical plan or visual outcome68. requires restoration of the transparency of the optical
Visual impairment can be assessed subjectively accord- pathway through replacement of the clouded crystal-
ing to the patients’ perception or by visual acuity meas- line lens with an IOL with appropriate refractive power.
urements. Visual acuities are recorded for both far and Current surgical techniques achieve these goals with
near distances. Assessment of the intraocular pressure, precision, reproducibility and safety owing to our ability
to measure the optical parameters of the eye, advanced
technologies to remove the cataract and continuing
a b c advances in IOL design (FIG. 4).
All modern techniques are variations of extracapsular
cataract surgery, in which most of the surrounding clear
lens capsule is preserved to permanently support the
IOL. Zonules (microscopic ligaments) attach and insert
circumferentially onto the lens capsular equator to sus-
pend and support the lens. After making a central open-
Nature Reviews | Disease Primers ing in the anterior capsule the large, firm lens nucleus
Figure 3 | Clinical presentation of cataract. a | A mild cataract presents as subtle
cloudiness of the lens. b | Moderate cataracts cause a more pronounced cloudiness. and softer surrounding cortex are removed. The IOL is
c | Mature cataracts lead to the complete opacification of the lens; the image shows a then placed within the vacated capsular bag, where it lies
white mature cataract. anterior to the remaining clear posterior capsule.

PRIMER
a Small incision Ultrasonic emulsification and Implantation of new,

aspiration of lens nucleus foldable lens
Diamond Phacoemulsification
knife needle
Posterior
capsule
Lens IOL
b Bigger, scleral incision Removal of lens nucleus Implantation of new lens
Crescent Lens expression

knife loop
c Laser-assisted incision, Ultrasonic emulsification and Implantation of new,

capsulorhexis and initial aspiration of lens nucleus foldable lens
lens fragmentation
Femtosecond
laser
Fixating
tool
Figure 4 | Simplified schematic diagram showing different technologies used for cataract Naturesurgery.
Reviews |aDisease
| For phaco
Primers
emulsification only a small incision into the cornea is needed. The lens nucleus is broken down by ultrasonic emulsification
and aspirated. A foldable intraocular lens (IOL) is inserted through the incision and implanted through the anterior
opening into the remaining capsule. b | In manual small-incision cataract surgery (M‑SICS) a slightly bigger but still
relatively small incision is needed. This creates a scleral tunnel through which the cataract can be removed and a new IOL
be implanted. c | Femtosecond laser-assisted cataract surgery (FLACS) is the newest technology used for cataract surgery.
The first steps of surgery (incision of cornea, opening of anterior capsule and partial fragmentation of lens) are automated
and carried out by laser.
Different surgical methods astigmatism. Astigmatism reduction and faster physical

Phacoemulsification. Phacoemulsification was first and visual rehabilitation in particular have made phaco-
developed by Charles Kelman in the late 1960s75 and emulsification the gold standard in developed countries
uses ultrasonic energy to vibrate a titanium needle for more than two decades. In developing countries, cost
at high frequencies, which fragments the rigid lens and other considerations drive the widespread use of
nucleus; the resulting emulsate is simultaneously aspi- manual techniques (see below).
rated from the eye (FIG. 4a). The benefit of phacoemulsi Although not a substitute for individual surgical skill,
fication over purely manual methods is the ability to advances in phacoemulsification and other surgical
extract the large nucleus through a small incision of technologies have improved the safety and reproducibil-
≤3.0 mm. Foldable IOLs are then implanted through this ity of small incision cataract surgery. This is particularly
small incision, which generally can be left unsutured. true for the most advanced cataracts that have larger
Improvements in machines and needles now enable sur- and harder nuclei76. As with any microsurgery, improve-
gery through mini-incisions of 2.2 mm or micro-incisions ments in surgical microscopes have been important.
of ≤1.8 mm. However, the use of micro-incisions requires Furthermore, advances have been made in viscoelastics,
special IOLs. Small incisions have numerous advantages: which are transparent viscous gels that the surgeon uses to
topical instead of local injection anaesthesia can be used, protect the intraocular structures from surgical trauma.
especially if the incision is made in the peripheral cor- Improved viscoelastics have reduced the risk of corneal
nea; the surgeon enjoys better control of the intraocular decompensation77 (corneal oedema resulting from failure
environment and greater safety should the patient of the corneal endothelium to keep the cornea relatively
move; structural integrity of the incision is quickly re- dehydrated). Other devices such as iris retractors, pupil
established and fewer physical restrictions are necessary expansion rings, capsule retractors and capsular tension
after surgery; and, finally, smaller incisions minimize rings facilitate successful surgery in challenging eyes
alterations of the corneal shape, which would cause with smaller pupils or abnormal zonules. Finally, dyes to

PRIMER
stain and enhance visibility of the anterior capsule have use essentially the same basic technology today that
improved the success rate with mature white cataracts. Charles Kelman first designed in the late 1960s. Early
Potential benefits from automating certain surgical steps attempts to use lasers to liquefy the lens nucleus proved
with femtosecond laser technology are being evaluated78. no better than ultrasonic emulsification; femtosecond
Most IOLs are made of acrylic plastic or silicone that lasers now provide a way to automate certain steps of
render the lens foldable. IOL research initially focused on the cataract procedure87–89 (FIG. 4c). FLACS was approved
developing the safest design. Further advances were made for cataract treatment in 2010 and represents a new
to optimize the optical properties. Modern IOLs block frontier in cataract surgery. However, the technique is
UV light, minimize unwanted optical spherical aberra- a relatively new technology and several issues need to
tion and inhibit secondary opacification of the posterior be addressed, including risks of pupil constriction and
capsule79. Similarly to other corrective lenses, IOLs come subconjunctival haemorrhage90.
in multiple refractive powers. New IOL designs address Femtosecond lasers are used to perform the corneal
astigmatism (toric lenses)80 and presbyopia (multifocal incision, the anterior capsular opening and partial frag-
lenses)81 to reduce the need for glasses. Modern technolo- mentation of the lens nucleus91,92. After the anaesthetized
gies and IOLs have transformed cataract surgery into one eye is docked to the laser instrument, 3D images of the
of the most common refractive procedures. cornea and lens are captured93. The infrared laser is then
programmed to deliver energy in extremely short pulses
M‑SICS and modified M‑SICS. Phacoemulsification is the to make tissue cuts that are automatically registered to
benchmark for cataract extraction in the developed world. and guided by these images. Traditional phacoemulsifi-
There are, however, a number of issues surrounding its use cation is then used to emulsify and extract the lens, and
in economically less-developed societies. It requires a sub- the remainder of the procedure, including IOL implanta-
stantial investment in the phacoemulsification equipment tion, is performed in the usual manual manner. Lasers
and much higher recurrent costs for medical consumables are also used to make partial-depth corneal incisions to
than are required by manual methods. Cost and expertise treat astigmatism94. This technique of astigmatic kera-
involved in equipment maintenance is also a concern in totomy is otherwise performed manually with special
developing countries. Moreover, compared with manual diamond blades.
cataract surgery, the phacoemulsification procedure Such automation offers the potential to improve both
usually takes more time and effort to learn — and the the safety and precision of surgical manoeuvres, and
required teaching facilities and capacities might be lack- many think that FLACS offers advantages for certain
ing in developing countries. Finally, the manual technique complicated eyes. However, there is no robust data show-
is a better choice for the hard and mature cataracts that are ing that FLACS improves visual or refractive outcomes
more common in poor populations. compared with traditional phacoemulsification. Indeed,
Accordingly, alternative surgical techniques have been substantial controversy surrounds FLACS because it adds
developed for cataract surgeries in developing countries. considerable expense, which usually has to be borne by
The most popular technique is a sutureless M-SICS82 the patient. Although the notion of laser-assisted surgery
(FIG. 4b). Modifications of the M‑SICS technique, includ- is conceptually appealing to patients, greater adoption of
ing sutureless large incision manual cataract extraction this costly technology will require convincing evidence
(SLIMCE)83–85, are gaining popularity, especially in of improved outcomes.
China. All of these modifications use a larger incision to
increase the safety of cataract removal and a long, suture- Prevention of endophthalmitis
less scleral tunnel incision to minimize astigmatism and Endophthalmitis is a visually devastating complication of
accelerate physical and visual recovery. cataract surgery with an incidence ranging from 0.028%
M‑SICS achieves excellent outcomes with lower to 0.345%95,96.
cost and surgical time than phacoemulsification. Aside Use of topical antibiotics starting 1–3 days pre-
from speed and affordability, M‑SICS is easier for less- operatively has been shown to reduce conjunctival
experienced surgeons to learn and, in their hands, is safer bacterial count 97. Broad-spectrum drugs such as the
for advanced mature cataracts. Furthermore, dropped fourth-generation fluoroquinolones are currently
nuclei — a serious complication of cataract surgery that being used routinely by some surgeons, but increas-
involves nucleus dislocation onto the retina — are rare ing drug resistance to fluoroquinolones has made their
with M‑SICS. This complication carries a poor prognosis use debatable. Povidone iodine is a broad-spectrum
if it is not properly managed by a vitreoretinal special antiseptic with bactericidal, virucidal and fungicidal
ist, which is a rare subspecialty in many developing properties, and it is applied before surgery for ocu-
countries. Both M‑SICS and phacoemulsification are safe lar antisepsis98,99. This prophylaxis reduces the risk of
and provide excellent visual outcomes86. postoperative endophthalmitis100,101.
Antibiotic prophylaxis can also be applied as a direct
Femtosecond laser-assisted cataract surgery. Since intra-cameral bolus at the end of surgery. A prospective
phacoemulsification became the most popular cata- randomized multicentre study initiated by the European
ract treatment in the early 1990s, numerous alternative Society of Cataract & Refractive Surgeons (ESCRS)
methods of liquefying or softening the cataract for small showed that intra-cameral cefuroxime reduced the inci-
incision extraction have been investigated. In what must dence of postoperative endophthalmitis fivefold69,102.
be considered a truly rare occurrence in medicine, we Intra-cameral injection guarantees supra-threshold

PRIMER
antibiotic levels for an extended period of time69, and this Many patients find it difficult to adapt to a large difference
mode of antibiosis is superior to subconjunctival injec- in focal points.
tion. No evidence suggests the use of antibiotics in irrigat- Multifocal IOLs114,115 have two or more separate focal
ing infusion fluid3. Cefuroxime does not increase the risk points. They have both a far and a near focal point,
of allergic reactions because it does not share molecular which improve near vision compared with monofocal
homology (in the side chains) with penicillin103 — an IOLs. However, there are optical trade-offs, including
often-used antibiotic that commonly causes allergies. reduced contrast sensitivity, halos or other unwanted
Recently, a single-unit dose of cefuroxime designed for images, and a greater reduction in overall image quality
intra-cameral use has been approved, which reduces the from residual astigmatism, refractive error and IOL tilt
risk of contamination and overdosage that can lead to or decentration. In addition, the uncorrected midrange
ocular toxicity 104. vision might not be optimal. Nevertheless, monofocal
Cefuroxime is a second-generation cephalosporin with monovision and multifocal IOLs can provide high levels
bactericidal action against many Gram-positive organ- of patient satisfaction116–118.
isms and some Gram-negative organisms. However, it Accommodating IOLs119 have long been sought
does not cover methicillin-resistant Staphylococcus aureus after as the functional equivalent of the natural lens.
(MRSA), some Enterococcus strains and Pseudomonas The concept is to have an IOL that shifts focus through
spp. Vancomycin and moxifloxacin have also been used a dynamic mechanism initiated by the ciliary muscle;
for intracameral prophylaxis95. Vancomycin is effec- however, single-optic (containing only one optic com-
tive against MRSA, but because it is the last drug avail- ponent) accommodating IOLs cannot achieve sufficient
able against many multidrug-resistant bacteria, its use as a levels of this type of control. Several accommodating IOL
prophylactic antibiotic is debated. The fourth-generation designs are under development and in varying stages of
fluoroquinolones, such as moxifloxacin, have a broader clinical evaluation.
antimicrobial spectrum than cefuroxime and high Extended depth of focus IOLs are monofocal IOLs
potency, but MRSA has developed resistance. that provide greater depth of focus through certain
There is no universally accepted consensus on a pre- design modifications, such as increasing spherical aber-
ferred protocol for asepsis, antisepsis and antibacterial ration of the optic. This improvement in focus range
prophylaxis. An international joint effort to produce is called pseudo-accommodation because dynamic
guidelines is much needed. alteration of either lens shape or position is lacking.
Several of these IOL designs are under development or
Refractive errors in clinical studies, and would lend themselves well to a
Astigmatism. Simultaneous reduction or elimination monovision strategy 120.
of pre-existing astigmatism during cataract surgery is a
common practice. The prevalence of astigmatic refrac- Complicated cataracts
tive errors varies from 32.3% to as high as 58.8%105. The As with any eye surgical procedure, some eyes present
correction during cataract surgery is achieved through challenging conditions that increase the surgical diffi-
neutralization of the pre-existing astigmatism by surgically culty and the risk of complications. Small pupils, mature
induced astigmatism106, peripheral corneal-relaxing inci- cataracts and weak zonules are the most common risk
sions107 or implantation of a toric IOL108–110. These meth- factors for surgical complications. Fortunately, advances
ods can be used in isolation or combination depending on in phacoemulsification technology, the development of
the degree of astigmatic correction needed111. Correction ancillary devices and better surgical training and experi
of astigmatism will contribute to a better postoperative ence have improved the prognosis of cataract surgery
visual outcome and lessen the need for glasses. performed on challenging eyes.
Presbyopia. Conventional monofocal IOLs do not pro- Small pupil. Small pupils pose problems for cataract
vide focus at all distances. Patients with good uncorrected surgery 121–123. The pupil is dilated with topical mydriatic
distance acuity require reading glasses to focus on near drugs for all cataract surgeries to improve the surgical
objects. Several strategies or technologies are available to access to, and visualization of, the lens nucleus, cortex
reduce the need for reading glasses after cataract surgery, and capsular structures. The width of pupil dilation in
including variable-focus lenses; the use of intracorneal response to dilating drops varies by individual. Limited
inlays that enable increased depth of focus and improved dilation poses a risk of surgical complications such as iris
near vision in the non-dominant eye; and special IOLs. trauma or tearing of the anterior or posterior capsule.
Monovision with monofocal IOLs112,113 enables a dif- Other causes of small pupils include synechiae (restric-
ferent focal point to be targeted in each eye. Accordingly, tive adhesions) and use of pupil-constricting medications,
the binocular patient is able to see across a broader range including pilocarpine and systemic α1-adrenergic receptor
of distances compared with having the same refraction antagonists (which are used, for example, to treat benign
in both eyes. A small difference is generally well toler- prostatic hyperplasia)124. Small pupils can be enlarged
ated and does not prevent binocularity; however, this intraoperatively by injecting α1-adrenergic receptor ago-
usually will not provide optimal uncorrected near focus. nists, such as phenylephrine or adrenaline, into the eye or
Achieving a larger difference in focal points might by inserting mechanical devices, such as iris retractors or
improve uncorrected reading ability but can impede pupil expansion rings, to temporarily expand the pupil
binocular summation, depth perception and stereopsis. (FIG. 5a).

PRIMER
Mature cataracts. If cataracts are not operated on, visual the lens cortex becomes liquefied to the point of turn-
function gets progressively worse and, in advanced states, ing milky white and opaque. This obscures the surgeon’s
cataracts can compromise the health of the eye (for exam- view of the anterior lens capsule and the underlying lens
ple, through secondary glaucoma or uveitis (inflamma- nucleus. Creating the anterior capsular opening is very
tion of the eye)). The most advanced cataracts are said difficult owing to poor visibility and the increased intra
to be mature125,126, and surgery on these lenses is more lenticular pressure caused by cortical liquefaction. Trypan
difficult and complication-prone. blue staining 129 of the anterior capsule improves surgical
Mature cataracts are of two types (brunescent and visualization and has advanced the management of these
white), depending on whether the lens nucleus or the cases substantially.
cortex has become opaque. In mature white cataracts127,128 As the transparent nucleus ages, it gradually becomes
discoloured before eventually turning opaque, and its
a colour changes from pale yellow to brown and eventually
Causes
Synechiae Inadequate response to Pupil-constricting even black. Brown cataracts are also called brunescent.
Complications
(adhesions) dilating eye drops drugs
Management
Besides changing colour, a maturing cataract nucleus
grows in size and becomes increasingly hard. Because
Small pupil
phacoemulsification requires ultrasonic vibration to
emulsify and fragment the solid nucleus, fragmentation
of brunescent nuclei requires more energy, and this is
Poor surgical visibility and access inherently more traumatic to the cornea and to the cap-
sular structures (FIG. 5b). Thus, the risk of corneal injury
and capsular tears is increased with brunescent cataracts.
Intracameral mydriatics Mechanical dilation
(α1-adrenergic (iris retractor or
receptor agonists) pupil-expanding rings) Zonular weakness. The zonules attach the lens capsule
to the ciliary body. Weakened or torn zonules (FIG. 5c)
b increase the risk of anterior and posterior capsular tears
Liquefaction of lens cortex Discolouration and hardening of lens nucleus during cataract surgery and can be associated with IOL
instability and can lead to late dislocation of the IOL and
the capsular bag many years postoperatively. Zonules can
Mature white cataract Mature brunescent cataract be torn as a result of prior ocular trauma or by certain sur-
gical manoeuvres. Diffuse zonular weakness can be associ-
Poor visibility and increased Increased risk of corneal injury ated with systemic conditions (such as Marfan syndrome),
lens pressure and capsular tearing ocular conditions (such as retinitis pigmentosa or retino
pathy of prematurity) and prior intraocular surgery 130.
Pseudo-exfoliation is a common age-related ocular disease
Trypan blue staining Modification of surgical preparation and procedure
associated with glaucoma, small pupils, northern European
ethnicity and progressive zonular weakening over time131.
c
Surgical management has been improved by the use
Prior trauma Eye diseases Systemic diseases of temporary retractors to support the capsular bag dur-
or intraocular (such as retinitis pigmentosa, retinopathy (such as Marfan ing surgery. In the long term, capsular stability can be
surgery of prematurity and pseudoexfoliation) syndrome)
improved by implantation of a permanent plastic capsular
tension ring132,133. Modified rings can also be fixated to the
Zonular weakness or torn zonules sclera with sutures to provide support of the capsular bag
in regions of torn or absent zonules.
Capsular instability during surgery and increased risk
of postoperative IOL dislocation Paediatric IOLs
Children’s eyes are not simply miniature adult eyes,
especially in regard to cataract surgery. Differences in
Support of the capsular Permanent stabilization of capsule the tensile strength of the various ocular tissues, a more
bag during surgery (implantation of a permanent capsular tension
(with temporary retractors) ring or scleral fixation with modified rings) reactive uveal tract, an increased proliferative capacity
in the residual lens cells, the continued growth of the
Figure 5 | Management of complicated cataracts. a | Small Naturepupils increase
Reviews the risk
| Disease of
Primers eye, changes in ocular dimensions after surgery, and the
complications because they reduce access and visibility during surgery. Administration immature visual system combine to make paediatric cata-
of pupil-dilating drugs directly into the anterior chamber of the eye or mechanical dilation ract surgery a substantial challenge, even for experienced
can help to enlarge the pupil. b | Two types of mature cataracts (white and brunescent) adult cataract surgeons134,135.
exist. White cataracts are caused by liquefaction of the lens cortex, and staining of the Improvements in paediatric cataract surgery have
otherwise clear capsule with trypan blue can help to overcome the poor surgical visibility.
resulted in better visual outcomes and fewer cases of
Brunescent cataracts affect the lens nucleus. They lead to substantial hardening of the
cataractous material, and therefore more energy is needed during surgery, which increases postoperative glaucoma. IOLs can now be placed success-
the risk of traumatic injury. c | Prior surgery or trauma and systemic or eye diseases can fully, most of the time, in the capsular bag, where they are
weaken the zonules, which hold the capsule in place. To provide stability during surgery, protected from the uveal tissues. More biocompatible IOL
temporary retractors can be used; for permanent stabilization, rings that are placed inside materials and foldable IOLs that require smaller incisions
the capsule or fixed to the sclera with sutures are used. IOL, intraocular lens. have reduced postoperative inflammation considerably135.

PRIMER
Box 2 | Intraocular lens power in childhood cataract

(paramedical personnel, buildings and utilities, instru-
ments and devices, and sterilization)144–146; recurring costs
Various strategies have been employed to determine intraocular lens power for (disposables and IOLs); costs for the patient to travel;
cataract surgery in children. In general, the aim is to the leave the eye mildly hyperopic medications; glasses (if required); and costs caused by
at the end of surgery to counter the continued myopic drift that occurs with age, but possible complications84,147 and their management. Some
there is no consensus as to the ideal approach143.
of these costs are borne by the patient (price to consumer);
One of the suggested approaches is age-based and aims for the following refractive
powers postoperatively:
the rest are the responsibility of the health-care system
• <2 years: +4 dioptre
(cost to provider).
The manner in which these costs are defrayed dif-
• 2–4 years: +3 dioptre
fers between developed and developing countries. In
• 4–6 years: +2 dioptre
many developed countries, insurance — either private
• 6–8 years: +1 dioptre or through state health-care systems — covers most of
• >8 years: ±0 dioptre (emmetropia) the cost. By contrast, in developing countries insurance
However, these and other similar guidelines are rules of thumb and need to be is often lacking and most of the cost, or often all of it,
modified for the individual patient on the basis of their clinical situation and the comes out of the patient’s pocket. Fortunately, in many
surgeon’s experience. of these countries, a tiered system of health care exists,
with various categories of health delivery systems (such
as tiered billing on the basis of patient income and sub
If the posterior capsule is left intact during cataract sidized procedures using cheaper, non-foldable IOLs); for
surgery in children, it will become opaque in almost all example, in India, cataract surgery costs for patients range
cases owing to the proliferation of epithelial cells. Initial from US$200 to $600 (REF. 148).
attempts to prevent this included the performance of a However, particularly in developing countries, many
primary posterior capsulorhexis (removal of the pos patients have no or very limited financial resources, and
terior capsule; during traditional cataract surgery only for them even the costs listed above can be prohibitive.
the anterior capsule is removed) and anterior vitrec- In India, various non-governmental agencies have estab-
tomy to remove the scaffold for proliferating lens cells. lished cost-effective programmes that provide safe, effec-
To avoid removal of the vitreous in these young eyes, tive interventions for cataract for such patients149. Most
which involves more invasive surgery and has more of these programmes include outreach and screening
risks than surgery without this procedure, the IOL can patients in villages; those with cataracts are then brought
be placed in the capsule and moved through the pos to the hospital for surgery, and postoperative care is pro-
terior capsulorhexis into the vitreous humour 136. A more vided at their village. Cost can be reduced by maximizing
recent approach — ‘bag‑in‑the-lens’ (BIL) — involves the use of available resources, including the use of reusable
an IOL with a circumferential groove into which the materials, which are generally less costly than disposables.
remaining outer ring of the capsule, which has not been Many of the centres providing such surgery also have ‘pay-
removed, fits137. When correctly placed, the lens itself ing sections’ for patients who can afford it, and part of
acts as a mechanical barrier, which restricts the access this income is used to subsidize the ‘free service’ section.
of proliferating lens epithelial cells and maintains a clear However, these centres depend on skilled surgeons who
visual axis137. Even if postoperative opacification develops, are willing to work for a cost-effective salary.
anterior vitrectomy and surgical capsulotomy seem to be In the above model, the patient does not have to pay
safe and effective138. at all, and the costs of the surgery are subsidized partly
IOL implantation in children younger than 1 year of from government grants, partly from voluntary dona-
age is controversial, although some major institutions tions from affluent members of society and partly from
around the world do not have an age limit for infants139,140. the hospital itself. These efforts have improved access
The lens attains 90% of its final size by the age of 2 years, to cataract surgery, which has resulted in a substantial
and further growth of the eye involves the posterior seg- reduction in the burden of cataract blindness in India149.
ment, which makes choosing the IOL power in children Similar efforts are ongoing in other parts of the develop-
<2 years of age difficult141 (BOX 2). ing world as well83,150–152. Cost-effective strategies require
Finally, even after effective cataract surgery using the a more holistic perspective that takes into account socio-
above strategies, amblyopia (‘lazy eye’ owing to impaired cultural elements and appropriate models of health care
vision development in childhood) remains a substantial and delivery 153,154.
problem, especially in unilateral cataracts and in older
children. Hence, intense efforts to stimulate the visual Quality of life
pathways of the affected eye in an effort to attain the Cataract extraction is one of the most commonly per-
maximum vision possible are mandatory after surgery. formed surgeries in the world. Successful surgeries lead to
Thus, despite the many advances in the field of paediatric a marked improvement of vision and quality of life155. This
cataract surgery, challenges remain, especially in children applies even to eyes with concomitant eye diseases, such
<1 year of age139,140,142,143. as age-related macular degeneration and glaucoma, and
to patients who have already undergone cataract surgery
Cost-effective strategies in their first eye156. In general, the visual improvements
The costs of cataract surgery can be attributed to the fol- from cataract surgery will benefit multiple domains of life,
lowing: training of surgeons; infrastructure and support including emotional and social life157.

PRIMER
Studies in populations with low income have shown technological improvements must always be balanced
long-lasting benefits — restored sight after cataract with cost to the patient and the health-care system. The
surgery improved health-related quality of life, well shift from a sutured extracapsular approach to phaco-
being, family wealth and spending power 158. Whether emulsification was a major advance and resulted in sub-
and how much cataract surgery-related improvement stantial patient benefits162. However, the steep increase
in vision reduces the risk of falls, hip fractures and other in costs prompted the development of a manual small
major accidents remain unclear 159. Cataract surgery incision procedure, and this is now commonly per-
improves cognitive function and psychological dis formed in developing countries, with excellent results.
orders160, which suggests that delayed surgery in elderly The introduction of FLACS does not provide the same
patients with severe cataract-related visual impairment major step in improvement of outcomes as the previous
might lead to partial intellectual deprivation and early example. However, FLACS has its proponents who think
cognitive dysfunction. that the increased precision is an advantage. Clearly, at
the present time, FLACS is not the preferred approach
Outlook in the developing world.
Overall picture
Globally, the age-standardized prevalence of cataract New refractive IOL technologies
showed a marked decline between 1990 and 2010. The Owing to several decades of improvements and advances
number of people affected by blindness and moderate in design, the IOL is the most commonly implanted
to severe visual impairment due to cataract decreased device in all of medicine. The term ‘medical miracle’ is
between 1990 and 2010 from 12.3 million to 10.8 mil- overused, but a relatively inexpensive device that can
lion, and from 44.0 million to 35.2 million, respectively 7. be folded and implanted through a micro-incision, that
In 2010, the prevalence of cataract as a cause for blind- never needs replacement, that is permanently held in
ness and moderate to severe visual impairment in people place by natural ocular structures, that provides visual
≥50 years of age was 0.7% and 2.2%, respectively. This clarity identical to that of a child and that can correct
represented a decline from 1.3% in 1990 for blindness, refractive error is just such a miracle to the blind patients
and 4.4% for moderate to severe visual impairment. The whose vision it restores.
decline of cataract as a cause for blindness and vision Young healthy crystalline lenses have the ability to
impairment was most marked in east Asia, tropical Latin accommodate and vary focus, and the development of
America and western Europe (with the age-standardized IOLs that can mimic this behaviour is the ultimate goal.
prevalence falling by more than half in all three regions, Two IOLs in varying stages of development and clini-
for both blindness and moderate to severe visual impair- cal trial exemplify the ongoing innovative approaches to
ment). The region with the smallest decline was east IOL technology 163. One of these novel approaches uses
sub‑Saharan Africa7. lenses with liquid optics to provide accommodation in
The battle against cataract blindness is an ongoing one: response to ciliary muscle contraction164–166. Small fluid
the incidence of cataract is constantly increasing owing to shifts of a silicone gel change the refractive curvature of
ageing populations161. Despite technological and surgical the lens to generate a dynamic shift towards near focus.
advances, much work needs to be done, and it is impera- However, although these IOLs show promise, they have
tive that appropriate strategies are formulated and imple- yet to be validated in large clinical trials and are best
mented worldwide. The goals can vary in different parts of considered experimental at the present time.
the world. In the developed world, the focus is on restor- IOLs come in multiple powers, and the surgeon
ing unaided visual acuity and a return to work as early as attempts to calculate and select the IOL power pre
possible. This has prompted the development of techno operatively that will produce the desired refractive out-
logies such as aspheric, multifocal and accommodating come. Variables such as astigmatism induced by the
IOLs, torsional-mode phacoemulsification and FLACS. incision or variation in the final axial location of the IOL
Cost is not the primary concern for these technologies. mean that the precise desired outcome is never assured.
By contrast, in the developing world the focus is on safe, Accordingly, the ability to change the IOL power post
reproducible cataract surgery, and cost is of paramount operatively, after the patient’s refraction has stabilized,
importance. Also, surgery has to overcome many barri- would be a very exciting prospect. Such non-invasive
ers, including poor patient education, social and cultural adjustments would enable the ophthalmologist to cor-
customs that prevent the patient from accessing health rect any residual refractive error, such as astigmatism
care, varied geographical conditions that affect the access or myopia. An approach to achieve this that is cur-
to health care, and a skewed distribution of resources, with rently being investigated is a light-adjustable monofocal
poor availability of quality services in the rural regions153. lens, which consists of a partially polymerized material
that can be crosslinked with UV light after implanta-
Technologies to stay tion to change the lens shape and provide the desired
Current methods of cataract surgery include M‑SICS, refractive adjustment167.
phacoemulsification and FLACS. Although the precision
of cataract surgery improves with the advent of newer New preventive strategies
technologies, so does the cost 154. Surgeons and patients The incidence of cataracts and the number of cataract sur-
welcome improvements in precision, especially those geries are increasing, but currently no validated therapies
that increase the safety of a surgical procedure. However, or nutritional interventions exist that can prevent or slow

PRIMER
cataract development. Cataract prevention might help to Summary

reduce the social and economic burden of the disease. The success of modern cataract surgery is the result of a
Commonly known antioxidants, such as vitamins A, C long and exciting process. Few other medical procedures
and E and carotenoids, as well as antioxidative and anti- have benefited as much from innovations in surgical
inflammatory phytochemicals might prevent or delay the and implantable technology. Because of the enormous
progression of cataract by scavenging free radicals and prevalence of cataract, few other medical procedures
upregulating glutathione expression168. Phytochemicals have enhanced the lives of so many patients. Improved
that could be used as nutritional supplements for cata- safety, prognosis and outcomes have enabled surgery to
ract prevention include flavonoids (found in green tea, be performed at increasingly earlier stages of cataract.
catechins, Ginkgo biloba and grape seed extract), antho However, ageing population demographics will esca-
cyanins (found in bilberries and blueberries), and stil- late the financial burden that is placed on almost every
benes (for example, resveratrol)169,170. Recent studies society to provide treatment for cataract. Currently, the
have shown that herbal molecules, including curcumin biggest challenge is to curtail and reduce cataract blind-
and epigallactocatechin‑3‑gallate, can inhibit amyloid ness in the developing world, where cataract accounts
formation and effectively disaggregate amyloid fibres171 for more than half of all blindness.
and might prevent crystallin aggregation. Furthermore, In the developed world, the refractive benefits of IOL
chemical chaperones, such as sodium 4‑phenylbutyrate implantation have made cataract surgery one of the most
and trimethylamine N‑oxide, which have been shown common refractive procedures in ophthalmology. With
to make truncated human γD‑crystallin soluble in cell further IOL advances, increasing numbers of patients
culture172, could also be anti-cataract agents. These small might opt to pay for surgery before developing a cata-
molecules can inhibit protein aggregation, stabilize ract that affects their vision substantially. This enables
unfolded mutant crystallin and rescue insoluble trun- many patients to also become independent of glasses,
cated crystallin, suggesting that they act on the protein and it reduces the overall economic burden of cataracts
unfolding pathway. on society.
1. Song, E. et al. Age-related cataract, cataract surgery 13. Haddad, N. M. N., Sun, J. K., Abujaber, S., 28. World Health Organization. Prevention of blindness
and subsequent mortality: a systematic review and Schlossman, D. K. & Silva, P. S. Cataract surgery and visual impairment. Global cataract surgical rates.
meta-analysis. PLoS ONE 9, e112054 (2014). and its complications in diabetic patients. World Health Organization [online], http://
2. Salomon, J. A. et al. Healthy life expectancy for 187 Semin. Ophthalmol. 29, 329–337 (2014). www.who.int/blindness/data_maps/cataract_surgery_
countries, 1990‑2010: a systematic analysis for the 14. Hashim, Z. & Zarina, S. Advanced glycation end rate/en/index.html (2004).
Global Burden Disease Study 2010. Lancet 380, products in diabetic and non-diabetic human subjects 29. Nangia, V., Jonas, J. B., Gupta, R., Khare, A.
2144–2162 (2012). suffering from cataract. Age 33, 377–384 (2011). & Sinha, A. Prevalence of cataract surgery and
3. Pathengay, A., Flynn, H. W., Isom, R. F. & Miller, D. 15. Gupta, V. B., Rajagopala, M. & Ravishankar, B. postoperative visual outcome in rural central India
Endophthalmitis outbreaks following cataract surgery: Etiopathogenesis of cataract: an appraisal. Central India Eye and Medical Study. J. Cataract
causative organisms, etiologies, and visual acuity Indian J. Ophthalmol. 62, 103–110 (2014). Refract. Surg. 37, 1932–1938 (2011).
outcomes. J. Cataract Refract. Surg. 38, 1278–1282 16. Shingleton, B. J., Crandall, A. S. & Ahmed, I. I. K. 30. Weinreb, O., Dovrat, A., Dunia, I., Benedetti, E. L.
(2012). Pseudoexfoliation and the cataract surgeon: & Bloemendal, H. UV‑A‑related alterations of young
References 1–3 show that cataract is the leading preoperative, intraoperative, and postoperative issues and adult lens water-insoluble α-crystallin, plasma
cause of reversible blindness and visual impairment related to intraocular pressure, cataract, and membranous and cytoskeletal proteins.
globally. intraocular lenses. J. Cataract Refract. Surg. 35, Eur. J. Biochem. 268, 536–543 (2001).
4. He, L., Sheehy, K. & Culbertson, W. Femtosecond 1101–1120 (2009). 31. Lampi, K. J. et al. Sequence analysis of βA3, βB3,
laser-assisted cataract surgery. Curr. Opin. 17. Bair, B., Dodd, J., Heidelberg, K. & Krach, K. Cataracts and βA4 crystallins completes the identification of the
Ophthalmol. 22, 43–52 (2011). in atopic dermatitis: a case presentation and review of major proteins in young human lens. J. Biol. Chem.
5. Reitblat, O. et al. Accuracy of predicted refraction with the literature. Arch. Dermatol. 147, 585–588 (2011). 272, 2268–2275 (1997).
multifocal intraocular lenses using two biometry 18. James, E. R. The etiology of steroid cataract. J. Ocul. 32. Moreau, K. L. & King, J. A. Protein misfolding and
measurement devices and multiple intraocular lens Pharmacol. Ther. 23, 403–420 (2007). aggregation in cataract disease and prospects for
power calculation formulas. Clin. Experiment. 19. Leuschen, J. et al. Association of statin use with prevention. Trends Mol. Med. 18, 273–282 (2012).
Ophthalmol. http://dx.doi.org/10.1111/ceo.12478 cataracts: a propensity score-matched analysis. JAMA 33. Roshan, M. et al. A novel human CRYGD mutation in
(2015). Ophthalmol. 131, 1427–1434 (2013). a juvenile autosomal dominant cataract. Mol. Vis. 16,
6. Lee, A. C., Qazi, M. A. & Pepose, J. S. Biometry 20. Liu, X., Wang, L., Du, C., Li, D. & Fan, Y. Mechanism 887–896 (2010).
and intraocular lens power calculation. Curr. Opin. of lens capsular rupture following blunt trauma: 34. Bloemendal, H. et al. Ageing and vision: structure,
Ophthalmol. 19, 13–17 (2008). a finite element study. Comput. Methods Biomech. stability and function of lens crystallins. Prog. Biophys.
7. Stevens, G. A. et al. Global prevalence of vision Biomed. Engin. 18, 914–921 (2015). Mol. Biol. 86, 407–485 (2004).
impairment and blindness: magnitude and temporal 21. Yu, Z., Schulmeister, K., Talebizadeh, N., References 32 and 34 show that changes in the
trends, 1990–2010. Ophthalmology 120, Kronschläger, M. & Söderberg, P. Temperature- arrangement and alterations of crystallin folding
2377–2384 (2013). controlled in vivo ocular exposure to 1090‑nm result in increasing rigidity of the lens and
8. Ono, K., Hiratsuka, Y. & Murakami, A. Global radiation suggests that near-infrared radiation eventually loss of transparency.
inequality in eye health: country-level analysis from the cataract is thermally induced. J. Biomed. Opt. 20, 35. Basak, A. et al. High-resolution X‑ray crystal structures
Global Burden of Disease Study. Am. J. Public Health 015003 (2015). of human γD crystallin (1.25 A) and the R58H mutant
100, 1784–1788 (2010). 22. Bitarafan Rajabi, A. et al. Ionizing radiation-induced (1.15 A) associated with aculeiform cataract. J. Mol.
References 7 and 8 show that blindness due to cataract in interventional cardiology staff. Biol. 328, 1137–1147 (2003).
cataract is more common in populations with low Res. Cardiovasc. Med. 4, e25148 (2015). 36. Hains, P. G. & Truscott, R. J. W. Post-translational
socioeconomic status and in developing countries. 23. Awan, K. J. Delayed cataract formation after alkali modifications in the nuclear region of young, aged,
9. Li, E. Y. et al. Prevalence of blindness and outcomes burn. Can. J. Ophthalmol. 10, 423–426 (1975). and cataract human lenses. J. Proteome Res. 6,
of cataract surgery in Hainan Province in South China. 24. Wu, R. et al. Smoking, socioeconomic factors, and 3935–3943 (2007).
Ophthalmology 120, 2176–2183 (2013). age‑related cataract: the Singapore Malay Eye study. 37. Hains, P. G. & Truscott, R. J. W. Proteome analysis
10. Pascolini, D. & Mariotti, S. P. Global estimates Arch. Ophthalmol. 128, 1029–1035 (2010). of human foetal, aged and advanced nuclear
of visual impairment: 2010. Br. J. Ophthalmol. 96, 25. McCarty, C. A. & Taylor, H. R. A review of the cataract lenses. Proteomics Clin. Appl. 2, 1611–1619
614–618 (2012). epidemiologic evidence linking ultraviolet radiation (2008).
This study shows that cataract is the leading cause and cataracts. Dev. Ophthalmol. 35, 21–31 (2002). 38. Serebryany, E. & King, J. A. The βγ‑crystallins:
of blindness. 26. West, S. K. et al. Sunlight exposure and risk of lens native state stability and pathways to aggregation.
11. Borrow, J. C. (ed.) Basic and Clinical Science Course, opacities in a population-based study: the Salisbury Prog. Biophys. Mol. Biol. 115, 32–41 (2014).
Section 11: Lens and Cataract. (American Academy Eye Evaluation project. JAMA 280, 714–718 (1998). 39. Kosinski-Collins, M. S., Flaugh, S. L. & King, J.
of Ophthalmology, 2014). 27. Lindblad, B. E., Håkansson, N. & Wolk, A. Smoking Probing folding and fluorescence quenching in human
12. Hodge, W. G., Whitcher, J. P. & Satariano, W. Risk cessation and the risk of cataract: a prospective γD crystallin Greek key domains using triple
factors for age-related cataracts. Epidemiol. Rev. 17, cohort study of cataract extraction among men. tryptophan mutant proteins. Protein Sci. 13,
336–346 (1995). JAMA Ophthalmol. 132, 253–257 (2014). 2223–2235 (2004).

PRIMER
40. Udupa, P. E. G. & Sharma, K. K. Effect of oxidized senile cortical cataract in the Han Chinese population. 84. Lam, D. S. C. et al. Endothelial cell loss and surgically
βB3‑crystallin peptide (152‑166) on thermal Mol. Vis. 18, 1247–1252 (2012). induced astigmatism after sutureless large-incision
aggregation of bovine lens γ-crystallins: identification 64. Su, S. et al. The associations between single nucleotide manual cataract extraction (SLIMCE).
of peptide interacting sites. Exp. Eye Res. 80, polymorphisms of DNA repair genes, DNA damage, Arch. Ophthalmol. 127, 1284–1289 (2009).
185–196 (2005). and age-related cataract: Jiangsu Eye Study. 85. Hayashi, K., Nakao, F. & Hayashi, F. Topographic analysis
41. Rao, G., Santhoshkumar, P. & Sharma, K. K. Anti- Invest. Ophthalmol. Vis. Sci. 54, 1201–1207 (2013). of early changes in corneal astigmatism after cataract
chaperone βA3/A1(102‑117) peptide interacting sites 65. Gillespie, R. L. et al. Personalized diagnosis and surgery. J. Cataract Refract. Surg. 19, 43–47 (1993).
in human αB-crystallin. Mol. Vis. 14, 666–674 (2008). management of congenital cataract by next-generation 86. Venkatesh, R. et al. Manual small incision cataract
42. Das, P., King, J. A. & Zhou, R. Aggregation of sequencing. Ophthalmology 121, 2124–2137 (2014). surgery: a review. Asia-Pacif. J. Ophthalmol. 1,
γ‑crystallins associated with human cataracts 66. Sun, W., Xiao, X., Li, S., Guo, X. & Zhang, Q. Exome 113–119 (2012).
via domain swapping at the C‑terminal β‑strands. sequencing of 18 Chinese families with congenital 87. Rao, S. K., Jhanji, V. & Fan, A. H. Femtosecond laser:
Proc. Natl Acad. Sci. USA 108, 10514–10519 (2011). cataracts: a new sight of the NHS gene. PLoS ONE 9, is it the way forward for cataract surgery? Asia-Pacif.
43. Metlapally, S. et al. Analysis of nuclear fiber cell e100455 (2014). J. Ophthalmol. 1, 3–4 (2012).
cytoplasmic texture in advanced cataractous lenses 67. Liao, J. et al. Meta-analysis of genome-wide association 88. Lawless, M. & Hodge, C. Femtosecond laser cataract
from Indian subjects using Debye-Bueche theory. studies in multiethnic Asians identifies two loci for surgery: an experience from Australia. Asia-Pacif.
Exp. Eye Res. 86, 434–444 (2008). age‑related nuclear cataract. Hum. Mol. Genet. 23, J. Ophthalmol. 1, 5–10 (2012).
44. Marsili, S. et al. Cataract formation in a strain of rats 6119–6128 (2014). 89. Moshirfar, M., Churgin, D. S. & Hsu, M. Femtosecond
selected for high oxidative stress. Exp. Eye Res. 79, 68. American Academy of Ophthalmology Preferred laser-assisted cataract surgery: a current review.
595–612 (2004). Practice Pattern Committee. Preferred Practice Pattern Middle East Afr. J. Ophthalmol. 18, 285–291 (2011).
45. Kosinski-Collins, M. S. & King, J. In vitro unfolding, Guidelines. Comprehensive Adult Medical Eye Evaluation. 90. Jun, J. H., Hwang, K. Y., Chang, S. D. & Joo, C.‑K.
refolding, and polymerization of human γD crystallin, (American Academy of Ophthalmology, 2010). Pupil‑size alterations induced by photodisruption
a protein involved in cataract formation. Protein Sci. 69. American Academy of Ophthalmology Preferred during femtosecond laser-assisted cataract surgery.
12, 480–490 (2003). Practice Pattern Committee. Preferred Practice Pattern J. Cataract Refract. Surg. 41, 278–285 (2015).
46. Flaugh, S. L., Kosinski-Collins, M. S. & King, J. Guidelines. Cataract in the Adult Eye. (American 91. Miháltz, K. et al. Internal aberrations and optical
Interdomain side-chain interactions in human γD Academy of Ophthalmology, 2011). quality after femtosecond laser anterior capsulotomy in
crystallin influencing folding and stability. Protein Sci. References 68 and 69 provide guidelines for the cataract surgery. J. Refract. Surg. 27, 711–716 (2011).
14, 2030–2043 (2005). clinical evaluation and management of cataract. 92. Conrad-Hengerer, I., Hengerer, F. H., Schultz, T. &
47. Moreau, K. L. & King, J. Hydrophobic core mutations Patients are evaluated for visual impairment, Dick, H. B. Effect of femtosecond laser fragmentation
associated with cataract development in mice symptoms and concomitant eye diseases that could on effective phacoemulsification time in cataract
destabilize human γD-crystallin. J. Biol. Chem. 284, influence the surgical plan and visual outcome. surgery. J. Refract. Surg. 28, 879–883 (2012).
33285–33295 (2009). 70. Rocha, K. M. et al. Higher-order aberrations of 93. Palanker, D. V. et al. Femtosecond laser-assisted
48. Acosta-Sampson, L. & King, J. Partially folded age‑related cataract. J. Cataract Refract. Surg. 33, cataract surgery with integrated optical coherence
aggregation intermediates of human γD-, γC-, 1442–1446 (2007). tomography. Sci. Transl. Med. 2, 58ra85 (2010).
and γS-crystallin are recognized and bound by human 71. Gus, P. I., Kwitko, I., Roehe, D. & Kwitko, S. Potential 94. Takács, A. I. et al. Central corneal volume and
αB-crystallin chaperone. J. Mol. Biol. 401, 134–152 acuity meter accuracy in cataract patients. J. Cataract endothelial cell count following femtosecond
(2010). Refract. Surg. 26, 1238–1241 (2000). laser‑assisted refractive cataract surgery compared
49. Dolinska, M. B., Sergeev, Y. V., Chan, M. P., Palmer, I. 72. Lin, Q. et al. Genetic variations and polymorphisms in to conventional phacoemulsification. J. Refract. Surg.
& Wingfield, P. T. N‑terminal extension of beta the ezrin gene are associated with age-related cataract. 28, 387–391 (2012).
B1‑crystallin: identification of a critical region that Mol. Vis. 19, 1572–1579 (2013). 95. Rudnisky, C. J., Wan, D. & Weis, E. Antibiotic choice
modulates protein interaction with beta A3‑crystallin. 73. Chong, E. W. & Wong, T. Y. Multivitamin supplements for the prophylaxis of post-cataract extraction
Biochemistry 48, 9684–9695 (2009). and cataract prevention. Ophthalmology 115, endophthalmitis. Ophthalmology 121, 835–841 (2014).
50. Pande, A. et al. Crystal cataracts: human genetic 597–598 (2008). 96. Pathengay, A. et al. Acute postoperative
cataract caused by protein crystallization. Proc. Natl 74. Milton, R. C., Sperduto, R. D., Clemons, T. E. & endophthalmitis following cataract surgery: a review.
Acad. Sci. USA 98, 6116–6120 (2001). Ferris, F. L. Centrum use and progression of age-related Asia-Pacif. J. Ophthalmol. 1, 35–42 (2012).
51. Goralska, M., Holley, B. L. & McGahan, M. C. cataract in the Age-Related Eye Disease Study: 97. Kessel, L. et al. Antibiotic prevention of postcataract
Overexpression of H− and L‑ferritin subunits in lens a propensity score approach. AREDS report No. 21. endophthalmitis: a systematic review and meta-
epithelial cells: Fe metabolism and cellular response Ophthalmology 113, 1264–1270 (2006). analysis. Acta Ophthalmol. http://dx.doi.org/10.1111/
to UVB irradiation. Invest. Ophthalmol. Vis. Sci. 42, 75. Linebarger, E. J., Hardten, D. R., Shah, G. K. & aos.12684 (2015).
1721–1727 (2001). Lindstrom, R. L. Phacoemulsification and modern 98. Lam, P. T. H., Hui, M., Young, A. L., Chan, C. Y.
52. Lou, M. F. Redox regulation in the lens. Prog. Retin. Eye cataract surgery. Surv. Ophthalmol. 44, 123–147 & Lam, D. S. C. Preoperative antisepsis with
Res. 22, 657–682 (2003). (1999). povidone‑iodine 5% in cataract surgery. Asia-Pacif.
53. Tessem, M.‑B., Midelfart, A., Cejková, J. & Bathen, T. F. This paper gives an overview of the development J. Ophthalmol. 1, 77–83 (2012).
Effect of UVA and UVB irradiation on the metabolic of phacoemulsification surgery for the treatment of 99. Ciulla, T. A., Starr, M. B. & Masket, S. Bacterial
profile of rabbit cornea and lens analysed by HR‑MAS cataract. endophthalmitis prophylaxis for cataract surgery: an
1H NMR spectroscopy. Ophthalmic Res. 38, 105–114 76. Tsui, P.‑H., Huang, C.‑C., Zhou, Q. & Shung, K. K. evidence-based update. Ophthalmology 109, 13–24
(2006). Cataract measurement by estimating the ultrasonic (2002).
54. Schafheimer, N., Wang, Z., Schey, K. & King, J. Tyrosine/ statistical parameter using an ultrasound needle 100. Nentwich, M. M. et al. Incidence of postoperative
cysteine cluster sensitizing human γD‑crystallin to transducer: an in vitro study. Physiol. Meas. 32, endophthalmitis from 1990 to 2009 using povidone-
ultraviolet radiation-induced photoaggregation in vitro. 513–522 (2011). iodine but no intracameral antibiotics at a single
Biochemistry 53, 979–990 (2014). 77. Glasser, D. B., Schultz, R. O. & Hyndiuk, R. A. The role academic institution. J. Cataract Refract. Surg. 41,
55. Mizdrak, J., Hains, P. G., Truscott, R. J. W., Jamie, J. F. of viscoelastics, cannulas, and irrigating solution 58–66 (2015).
& Davies, M. J. Tryptophan-derived ultraviolet filter additives in post-cataract surgery corneal edema: 101. Packer, M. et al. Prevention, diagnosis, and management
compounds covalently bound to lens proteins are a brief review. Lens Eye Tox. Res. 9, 351–359 (1992). of acute postoperative bacterial endophthalmitis.
photosensitizers of oxidative damage. Free Radic. Biol. 78. Sutton, G., Bali, S. J. & Hodge, C. Femtosecond cataract J. Cataract Refract. Surg. 37, 1699–1714 (2011).
Med. 44, 1108–1119 (2008). surgery: transitioning to laser cataract. Curr. Opin. 102. Endophthalmitis Study Group, European Society
56. Vrensen, G. F. J. M. et al. Tryptophan deficiency arrests Ophthalmol. 24, 3–8 (2013). of Cataract & Refractive Surgeons. Prophylaxis of
chromatin breakdown in secondary lens fibers of rats. This paper gives an overview of the development postoperative endophthalmitis following cataract
Exp. Eye Res. 78, 661–672 (2004). of FLACS for the treatment of cataract. surgery: results of the ESCRS multicenter study and
57. Giblin, F. J. et al. UVA light in vivo reaches the nucleus 79. Mainster, M. A. & Sparrow, J. R. How much blue light identification of risk factors. J. Cataract Refract. Surg.
of the guinea pig lens and produces deleterious, should an IOL transmit? Br. J. Ophthalmol. 87, 33, 978–988 (2007).
oxidative effects. Exp. Eye Res. 75, 445–458 (2002). 1523–1529 (2003). 103. Pichichero, M. E. Cephalosporins can be prescribed
58. Shiels, A. & Hejtmancik, J. F. Genetics of human 80. Lockington, D., Wang, E. F., Patel, D. V., Moore, S. P. safely for penicillin-allergic patients. J. Fam. Pract. 55,
cataract. Clin. Genet. 84, 120–127 (2013). & McGhee, C. N. J. Effectiveness of cataract 106–112 (2006).
This study shows the influence of genetics on phacoemulsification with toric intraocular lenses in 104. Barry, P. Adoption of intracameral antibiotic
cataract development. addressing astigmatism after keratoplasty. J. Cataract prophylaxis of endophthalmitis following cataract
59. Chen, Y. et al. Effect of HSF4b on age related cataract Refract. Surg. 40, 2044–2049 (2014). surgery: update on the ESCRS Endophthalmitis Study.
may through its novel downstream target Hif1α. 81. Gundersen, K. G. & Potvin, R. Comparative visual J. Cataract Refract. Surg. 40, 138–142 (2014).
Biochem. Biophys. Res. Commun. 453, 674–678 performance with monofocal and multifocal intraocular 105. Wolfram, C. et al. Prevalence of refractive errors in
(2014). lenses. Clin. Ophthalmol. 7, 1979–1985 (2013). the European adult population: the Gutenberg Health
60. Dave, A. et al. Mutations in the EPHA2 gene are a This paper gives an overview of different lenses used Study (GHS). Br. J. Ophthalmol. 98, 857–861 (2014).
major contributor to inherited cataracts in South- for the treatment of cataract. 106. Lever, J. & Dahan, E. Opposite clear corneal incisions
Eastern Australia. PLoS ONE 8, e72518 (2013). 82. Tabin, G., Chen, M. & Espandar, L. Cataract surgery to correct pre-existing astigmatism in cataract surgery.
61. Zhang, Y. et al. Genetic polymorphisms of superoxide for the developing world. Curr. Opin. Ophthalmol. 19, J. Cataract Refract. Surg. 26, 803–805 (2000).
dismutases, catalase, and glutathione peroxidase in 55–59 (2008). 107. Rückl, T. et al. Femtosecond laser-assisted intrastromal
age-related cataract. Mol. Vis. 17, 2325–2332 (2011). 83. Lam, D. S. C. et al. Visual outcomes and astigmatism arcuate keratotomy to reduce corneal astigmatism.
62. Zhang, Y. et al. Genetic polymorphisms in DNA repair after sutureless, manual cataract extraction in rural J. Cataract Refract. Surg. 39, 528–538 (2013).
genes OGG1, APE1, XRCC1, and XPD and the risk of China: study of cataract outcomes and up‑take of 108. Visser, N., Nuijts, R. M. M. A., de Vries, N. E. &
age-related cataract. Ophthalmology 119, 900–906 services (SCOUTS) in the caring is hip project, report 1. Bauer, N. J. C. Visual outcomes and patient satisfaction
(2012). Arch. Ophthalmol. 125, 1539–1544 (2007). after cataract surgery with toric multifocal intraocular
63. Jiang, Z., Liang, K., Zhang, Q. & Tao, L. Glutathione This paper gives an overview of manual surgery for lens implantation. J. Cataract Refract. Surg. 37,
S‑transferases polymorphisms confer susceptibility to the treatment of cataract. 2034–2042 (2011).

PRIMER
109. Koch, D. D., Jenkins, R. B., Weikert, M. P., Yeu, E. & 134. Robbins, S. L., Breidenstein, B. & Granet, D. B. This paper shows that successful cataract surgery
Wang, L. Correcting astigmatism with toric intraocular Solutions in pediatric cataracts. Curr. Opin. Ophthalmol. improves vision and quality of life.
lenses: effect of posterior corneal astigmatism. 25, 12–18 (2014). 156. Lee, B. S., Munoz, B. E., West, S. K. & Gower, E. W.
J. Cataract Refract. Surg. 39, 1803–1809 (2013). 135. Gimbel, H. V. Posterior continuous curvilinear Functional improvement after one- and two-eye cataract
110. Visser, N., Bauer, N. J. C. & Nuijts, R. M. M. A. Toric capsulorhexis and optic capture of the intraocular lens surgery in the Salisbury Eye Evaluation. Ophthalmology
intraocular lenses: historical overview, patient selection, to prevent secondary opacification in pediatric cataract 120, 949–955 (2013).
IOL calculation, surgical techniques, clinical outcomes, surgery. J. Cataract Refract. Surg. 23 (Suppl. 1), 157. Ishii, K., Kabata, T. & Oshika, T. The impact of cataract
and complications. J. Cataract Refract. Surg. 39, 652–656 (1997). surgery on cognitive impairment and depressive mental
624–637 (2013). 136. Tassignon, M.‑J. B. R., De Groot, V. & status in elderly patients. Am. J. Ophthalmol. 146,
111. Mozayan, E. & Lee, J. K. Update on astigmatism Vrensen, G. F. J. M. Bag‑in‑the-lens implantation 404–409 (2008).
management. Curr. Opin. Ophthalmol. 25, 286–290 of intraocular lenses. J. Cataract Refract. Surg. 28, This paper shows that successful cataract surgery
(2014). 1182–1188 (2002). improves mental and cognitive status in elderly
112. Xiao, J., Jiang, C. & Zhang, M. Pseudophakic 137. Tassignon, M.‑J. et al. Bag‑in‑the-lens intraocular lens patients.
monovision is an important surgical approach to being implantation in the pediatric eye. J. Cataract Refract. 158. Danquah, L. et al. The long term impact of cataract
spectacle-free. Indian J. Ophthalmol. 59, 481–485 Surg. 33, 611–617 (2007). surgery on quality of life, activities and poverty: results
(2011). 138. Lam, D. S. C. et al. 25‑gauge transconjunctival from a six year longitudinal study in Bangladesh and
113. Ito, M., Shimizu, K., Niida, T., Amano, R. & Ishikawa, H. sutureless vitrectomy system in the surgical the Philippines. PLoS ONE 9, e94140 (2014).
Binocular function in patients with pseudophakic management of children with posterior capsular 159. McGwin, G., Gewant, H. D., Modjarrad, K., Hall, T. A.
monovision. J. Cataract Refract. Surg. 40, opacification. Clin. Experiment. Ophthalmol. 33, & Owsley, C. Effect of cataract surgery on falls and
1349–1354 (2014). 495–498 (2005). mobility in independently living older adults. J. Am.
114. De Vries, N. E. & Nuijts, R. M. M. A. Multifocal 139. Kleinmann, G., Zaugg, B., Apple, D. J. & Bleik, J. Geriatr. Soc. 54, 1089–1094 (2006).
intraocular lenses in cataract surgery: literature review Pediatric cataract surgery with hydrophilic acrylic 160. Chandrasekaran, S., Wang, J. J., Rochtchina, E. &
of benefits and side effects. J. Cataract Refract. Surg. intraocular lens. J. AAPOS 17, 367–370 (2013). Mitchell, P. Change in health-related quality of life after
39, 268–278 (2013). 140. Mataftsi, A., Dabbagh, A., Moore, W. & Nischal, K. K. cataract surgery in a population-based sample. Eye 22,
115. Braga-Mele, R. et al. Multifocal intraocular lenses: Evaluation of whether intracameral dexamethasone 479–484 (2008).
relative indications and contraindications for predisposes to glaucoma after pediatric cataract This paper shows that successful cataract surgery
implantation. J. Cataract Refract. Surg. 40, 313–322 surgery. J. Cataract Refract. Surg. 38, 1719–1723 improves health-related quality of life.
(2014). (2012). 161. Bourne, R. R. A. et al. Causes of vision loss worldwide,
116. Prakash, G., Prakash, D. R., Agarwal, A., Kumar, D. A. 141. McClatchey, S. K. Choosing IOL power in pediatric 1990‑2010: a systematic analysis. Lancet Glob. Health
& Jacob, S. Predictive factor and kappa angle analysis cataract surgery. Int. Ophthalmol. Clin. 50, 1, e339–e349 (2013).
for visual satisfactions in patients with multifocal IOL 115–123 (2010). 162. Liu, J., Xu, J. & He, M. [Comparing patients’ quality of life
implantation. Eye 25, 1187–1193 (2011). 142. Fan, D. S. P., Rao, S. K., Yu, C. B. O., Wong, C. Y. after phacoemulsification with intraocular lens
117. Wilkins, M. R. et al. Randomized trial of multifocal & Lam, D. S. C. Changes in refraction and ocular implantation with that after extracapsular cataract
intraocular lenses versus monovision after bilateral dimensions after cataract surgery and primary extraction with intraocular lens implantation]. Zhonghua.
cataract surgery. Ophthalmology 120, 2449–2455 intraocular lens implantation in infants. J. Cataract Yan Ke Za Zhi. 39, 94–97 (2003) (in Chinese).
(2013). Refract. Surg. 32, 1104–1108 (2006). 163. Waring, G. O. & Berry, D. E. Advances in the surgical
118. Artigas, J. M., Menezo, J. L., Peris, C., Felipe, A. 143. Lam, D. S. et al. Short-term results of scleral intraocular correction of presbyopia. Int. Ophthalmol. Clin. 53,
& Díaz‑Llopis, M. Image quality with multifocal lens fixation in children. J. Cataract Refract. Surg. 24, 129–152 (2013).
intraocular lenses and the effect of pupil size: 1474–1479 (1998). 164. Hao, X. et al. High refractive index polysiloxane as
comparison of refractive and hybrid refractive- 144. Kelman, C. D. Phaco-emulsification and aspiration. injectable, in situ curable accommodating intraocular
diffractive designs. J. Cataract Refract. Surg. 33, A new technique of cataract removal. A preliminary lens. Biomaterials 33, 5659–5671 (2012).
2111–2117 (2007). report. Am. J. Ophthalmol. 64, 23–35 (1967). 165. Nishi, O., Nishi, K., Nishi, Y. & Chang, S. Capsular bag
119. Patel, S., Alió, J. L. & Feinbaum, C. Comparison of Acri. 145. Jaggernath, J., Gogate, P., Moodley, V. & Naidoo, K. S. refilling using a new accommodating intraocular lens.
Smart multifocal IOL, crystalens AT‑45 accommodative Comparison of cataract surgery techniques: safety, J. Cataract Refract. Surg. 34, 302–309 (2008).
IOL, and Technovision presbyLASIK for correcting efficacy, and cost-effectiveness. Eur. J. Ophthalmol. 24, 166. Nishi, O., Nishi, Y., Chang, S. & Nishi, K.
presbyopia. J. Refract. Surg. 24, 294–299 (2008). 520–526 (2014). Accommodation amplitudes after an accommodating
120. Alio, J. L., Abdelghany, A. A. & Fernández-Buenaga, R. 146. Helvacioglu, F., Yeter, C., Sencan, S., Tunc, Z. & intraocular lens refilling procedure: in vivo update.
Enhancements after cataract surgery. Curr. Opin. Uyar, O. M. Comparison of two different ultrasound J. Cataract Refract. Surg. 40, 295–305 (2014).
Ophthalmol. 26, 50–55 (2015). methods of phacoemulsification. Am. J. Ophthalmol. 167. Helzner, J. The Calhoun adjustable IOL breaks new
121. Fine, I. H. Pupilloplasty for small pupil 158, 221–226.e1 (2014). ground. Ophthalmol. Manag. 18, 50–52 (2014).
phacoemulsification. J. Cataract Refract. Surg. 20, 147. Wilczynski, M. et al. Comparison of early corneal 168. Bhadada, S. V., Bhadada, V. J. & Goyal, R. K. Preventive
192–196 (1994). endothelial cell loss after coaxial phacoemulsification effect of Tephrosia purpurea on selenite-induced
122. Agarwal, A. et al. Modified Malyugin ring iris expansion through 1.8 mm microincision and bimanual experimental cataract. Curr. Eye Res. http://dx.doi.org/
technique in small-pupil cataract surgery with posterior phacoemulsification through 1.7 mm microincision. 10.3109/02713683.2015.1011281 (2015).
capsule defect. J. Cataract Refract. Surg. 34, J. Cataract Refract. Surg. 35, 1570–1574 (2009). 169. Orhan, H., Marol, S., Hepşen, I. F. & Sahin, G. Effects
724–726 (2008). 148. Neel, S. T. A cost and policy analysis comparing of some probable antioxidants on selenite-induced
123. Lam, D. S. C. & Wong, V. in A–Z in Ophthalmology immediate sequential cataract surgery and delayed cataract formation and oxidative stress-related
Book 4 Ch. 2 6–11 (Bon Vision Limited, 2009). sequential cataract surgery from the physician parameters in rats. Toxicology 139, 219–232 (1999).
124. Chang, D. F. & Campbell, J. R. Intraoperative floppy perspective in the United States. JAMA Ophthalmol. 170. Yamakoshi, J., Saito, M., Kataoka, S. & Tokutake, S.
iris syndrome associated with tamsulosin. J. Cataract 132, 1359–1362 (2014). Procyanidin-rich extract from grape seeds prevents
Refract. Surg. 31, 664–673 (2005). 149. Johns, A. W. The role of international non-governmental cataract formation in hereditary cataractous (ICR/f) rats.
125. Kimura, H. et al. Extracapsular cataract extraction with organisations in dealing with cataract blindness in J. Agr. Food Chem. 50, 4983–4988 (2002).
a sutureless incision for dense cataracts. J. Cataract developing countries. Doc. Ophthalmol. 81, 345–348 171. Shukla, S. M. & Sharma, S. K. Sinomenine inhibits
Refract. Surg. 25, 1275–1279 (1999). (1992). microglial activation by Aβ and confers neuroprotection.
126. Singh, R., Vasavada, A. R. & Janaswamy, G. 150. Congdon, N. G. et al. Visual function and postoperative J. Neuroinflamm. 8, 117 (2011).
Phacoemulsification of brunescent and black cataracts. care after cataract surgery in rural China: study of 172. Gong, B., Zhang, L.‑Y., Lam, D. S.‑C., Pang, C.‑P.
J. Cataract Refract. Surg. 27, 1762–1769 (2001). cataract outcomes and up‑take of services (SCOUTS) & Yam, G. H.‑F. Sodium 4‑phenylbutyrate ameliorates
127. Chakrabarti, A. & Singh, S. Phacoemulsification in eyes in the caring is hip project, report 2. the effects of cataract-causing mutant γD-crystallin
with white cataract. J. Cataract Refract. Surg. 26, Arch. Ophthalmol.125, 1546–1552 (2007). in cultured cells. Mol. Vis. 16, 997–1003 (2010).
1041–1047 (2000). 151. Zhou, Z. et al. Distribution and visual impact of 173. World Health Organization. Prevention of blindness and
128. Vasavada, A., Singh, R. & Desai, J. Phacoemulsification postoperative refractive error after cataract surgery in visual impairment. Fact sheet Global Data 2010 full set
of white mature cataracts. J. Cataract Refract. Surg. rural China: study of cataract outcomes and up‑take of 1–5 [online], http://www.who.int/blindness/data_maps/
24, 270–277 (1998). services report 4. J. Cataract Refract. Surg. 33, VIFACTSHEETGLODAT2010full.pdf?ua=1 (2010).
129. Wong, V. W. Y., Lai, T. Y. Y., Lee, G. K. Y., Lam, P. T. H. 2083–2090 (2007).
& Lam, D. S. C. A prospective study on trypan blue 152. Zhang, X. J. et al. Barriers for poor cataract surgery Acknowledgements
capsule staining under air versus under viscoelastic. uptake among patients with operable cataract in a The authors express their gratitude to E. X. Y. Liang for her
Eye 20, 820–825 (2006). program of outreach screening and low-cost surgery contributions to technical editing and refining references.
130. Arbisser, L. B. Managing intraoperative complications in rural China. Ophthalm. Epidemiol. 21, 153–160
in cataract surgery. Curr. Opin. Ophthalmol. 15, 33–39 (2014). Author contributions
(2004). 153. Martin, A. I., Sutton, G. & Hodge, C. The evolution Introduction (S.K.R., V.R., D.L. and D.F.C.); Epidemiology
This paper discusses complications of cataract of cataract surgery: controversies through the ages. (P.M. and J.J.); Mechanisms/pathophysiology (J.K., C.P.P. and
surgery. Asia‑Pacif. J. Ophthalmol. 2, 213–216 (2013). V.R.); Diagnosis, screening and prevention (Y.L. and V.R.);
131. Sangal, N. & Chen, T. C. Cataract surgery in 154. Shah, P. A. & Yoo, S. Innovations in phacoemulsification Management (S.K.R., D.F.C., D.L., Y.L., V.R. and M.T.); Quality
pseudoexfoliation syndrome. Semin. Ophthalmol. 29, technology. Curr. Opin. Ophthalmol. 18, 23–26 of life (J.J. and V.R.); Outlook (S.K.R., J.J., D.F.C., V.R., J.K.
403–408 (2014). (2007). and D.L.); overview of Primer (D.L.).
132. Hasanee, K., Butler, M. & Ahmed, I. I. K. Capsular References 153 and 54 demonstrate the ongoing
tension rings and related devices: current concepts. battle against cataract blindness and evaluate new Competing interests statement
Curr. Opin. Ophthalmol. 17, 31–41 (2006). developments. M.T. holds a patent on the BIL and ring caliper licensed to
133. Lam, D. S. et al. Scleral fixation of a capsular tension 155. Lamoureux, E. L., Fenwick, E., Pesudovs, K. & Tan, D. Morcher (Germany), which results in royalties. D.F.C. is a
ring for severe ectopia lentis. J. Cataract Refract. Surg. The impact of cataract surgery on quality of life. consultant for AMO, Calhoun Vision, Power Vision and LensAR.
26, 609–612 (2000). Curr. Opin. Ophthalmol. 22, 19–27 (2011). All other authors declare no competing financial interests.
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Article in Nature Reviews Disease Primers · June 2015

Vineet Ratra Paul Mitchell

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Jonathan King Marie-Jose Tassignon

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managing excess weight in children View project

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a Small incision Ultrasonic emulsiﬁcation and Implantation of new,

b Bigger, scleral incision Removal of lens nucleus Implantation of new lens

Crescent Lens expression

c Laser-assisted incision, Ultrasonic emulsiﬁcation and Implantation of new,

Different surgical methods astigmatism. Astigmatism reduction and faster physical

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Box 2 | Intraocular lens power in childhood cataract

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cataract development. Cataract prevention might help to Summary

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