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

Correspondence to D.L.
e-mail: dlam.sklo.sysu.cn@
gmail.com
State Key Laboratory of
Ophthalmology, and
Zhongshan Ophthalmic
Center, Sun Yat-Sen
University, 54 South Xianlie
Road, Guangzhou 510060,
China.
Article number: 15014
doi:10.1038/nrdp.2015.14
Published online
11 June 2015
The crystalline lens is a transparent, biconvex struc-
ture in the human eye that functions in a similar way
to the lens of a camera. A cataract is a lens abnormality
character­ized by decreased transparency and increased
cloudiness. Cataract is the leading cause of reversible vis-
ual impairment and blindness globally 1. The condition is
most prevalent in populations with lower socioeconomic
status and developing countries.
Crystallins are the main proteins making up the lens
and the lens surfaces, and are responsible for their refrac-
tive function. Modification, aggregation and precipita-
tion of crystallins are the main mechanisms underlying
cataract development. So far, no method that can prevent
this process has been found. Most cataracts are caused
by age-related degeneration; however, cataract can
also develop secondary to trauma or as a consequence
of another disease. Cataract rarely occurs in c­hildren
(see BOX 1 for an overview of the types of cataract).
The only treatment for cataract is surgical removal
of the lens and replacement with a permanent artifi­
cial intraocular lens (IOL). Successful cataract sur-
gery universally improves vision and quality of life.
Phacoemulsification (ultrasonic emulsification of the
lens contents, also known as phaco) is the gold standard
for cataract surgery in the developed world. By contrast,
manual small incision cataract surgery (M‑SICS) with a
self-sealing and sutureless incision is commonly used in
low- and middle-income countries. Both phacoemulsi­
fication and M‑SICS achieve excellent visual results;
more than 13 million cataract surgeries were performed
glo­bally in 2013 (REFS 1,2). Simultaneous correction of
refractive errors, such as astigmatism (blurred vision
mainly due to uneven curvatures of the cornea) and
presbyopia (age-related defect in focus on near objects),
reduces the need for glasses and is now an important
consideration of mo­dern cataract surgery.
Various risk factors can complicate cataract surgery,
leading, for example, to a small pupil or to rupture of the
posterior capsule during surgery. However, if properly
managed, most complications are still compatible with
good visual outcomes. Endophthalmitis (an inflamma-
tory condition of the intraocular cavities usually caused
by infection)3 is the most serious sight-threatening com-
plication, but its incidence is low and might be declining
with increased use of intracameral antibiotics injected
into the anterior chamber of the eye during surgery.
The success and functional outcomes of cataract sur-
gery have been greatly enhanced by advances in surgical
procedures, training and technology. Femtosecond laser-
assisted cataract surgery (FLACS)4 is able to automate
several steps of the procedure. However, this techno­
logy adds substantial cost, and significant differences in
visual outcomes or complication rates compared with
phacoemulsification have yet to be proven. IOL techno­
logy continues to improve and is the focus of much
research and development. Much of this innovation is
directed at reducing the patient’s need to wear glasses.
To enable increased precision in the selection of these

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PRIMER
Author addresses
1
State Key Laboratory of Ophthalmology, and Zhongshan Ophthalmic Center,
Sun Yat-Sen University, 54 South Xianlie Road, Guangzhou 510060, China.
2
C‑MER (Shenzhen), Dennis Lam Eye Hospital, Shenzhen, China.
3
Darshan Eye Clinic, Chennai, India.
4
Department of Ophthalmology, Centre for Vision Research, Westmead Hospital,
University of Sydney, Sydney, Australia.
5
Department of Biology, Massachusetts Institute of Technology, Cambridge,
Massachusetts, USA.
6
Department of Ophthalmology, Antwerp University Hospital, Brussels, Belgium.
7
Department of Ophthalmology, Ruprecht-Karls-University, Heidelberg, Germany.
8
Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong,
Hong Kong, China.
9
Department of Ophthalmology, University of California, San Francisco, California, USA.
‘premium’ IOLs, methods have been developed to accu-
rately measure the biometric parameters of the cata-
ractous eye using optical interferometry. This method
is more accurate than the traditionally used ultrasound
biometry 5. Furthermore, the formulae to calculate the
IOL power have improved, which ensure that the final
refractive outcome of cataract surgery is excellent 6.
As exciting as these technologies are, the greatest
challenge remains the growing prevalence and ‘back-
log’ of patients with cataract blindness in the develop-
ing world. In these countries, there is a lack of access to
affordable surgery, and efforts aimed at training cataract
Box 1 | Main types of cataract
Age-related cataract
• Most common form of cataract
• Usually develops in individuals >50 years of age
Childhood cataracts
• Congenital (present at birth)
• Juvenile (develops after birth)
• Usually caused by genetic conditions, congenital
disorders or intrauterine infections
Secondary cataract
• After trauma or surgery of the eye
• Caused by other eye disease (for example, glaucoma
or infection of the eye)
• Caused by certain drugs (for example, corticosteroids)
or radiation exposuer
• Associated with systemic diseases (for example,
diabetes mellitus)
Morphological classification
• Subcapsular (see illustration, left)
• Nuclear (see illustration, middle)
• Cortical (see illustration, right)
Nature Reviews | Disease Primers
2 | 2015 | VOLUME 1
© 2015 Macmillan Publishers Limited. All rights reserved
surgeons do not keep pace with the changing popula-
tion demographics and increasing rates of age-related
cataract. As no methods to prevent or delay cataract
development are currently available, greater attention is
needed to guarantee effective delivery of cataract sur-
gery in underserved regions. In this Primer, we discuss
the epidemiology, mechanisms, pathophysiology and
molecular genetics of cataract. We consider strategies to
address cost-effectiveness and quality of life and give an
outlook of future developments in cataract prevention
and management.
Epidemiology
According to the 2010 Global Burden of Disease Study 2
and other worldwide meta-analyses7,8, 32.4 million
individuals worldwide were blind (visual acuity <3/60;
with 60/60 representing normal vision) and 191 million
individuals were visually impaired (visual acuity <20/60
but ≥3/60) in 2010. Globally, the leading overall cause of
blindness was cataract, followed by uncorrected refrac-
tive error; uncorrected refractive error was the leading
global cause of moderate to severe visual impairment,
followed by cataract. This frequency-based ranking did
not change between 1990 and 2010. However, large dif-
ferences in the causes of blindness were apparent when
analysed according to region. In 2010, the percentage of
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-
age of moderate to severe visual impairment caused by
cataract was smallest in higher socioeconomic regions
(13.0–13.8%) and largest in south and southeast Asia
(both >20%) (FIG. 1). Across all regions, women had a
larger percentage of blindness (35.5% versus 30.1%) and
moderate to severe visual impairment (20.2% versus
15.9%) caused by cataract than did men.
Risk factors
Adult-onset cataract is primarily age related11. In fact,
the most important factor associated with cataract is age;
almost everyone living long enough will develop cata-
ract 12. Development of cataract is accelerated by meta-
bolic conditions such as diabetes mellitus13. Diabetic
individuals develop cataracts approximately 20 years
earlier and undergo cataract surgery for visually signifi-
cant cataracts at a much younger age than people with-
out diabetes13,14. Other metabolic conditions that cause
cataract include hypocalcaemia, Wilson disease and
myotonic dystrophy 15. There is an increased incidence
of cataract in patients with pseudo-exfoliation syndrome
and atopic dermatitis16,17. Ischaemic ocular conditions
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
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 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
cataract than acid injuries23. Ocular conditions caus-
ing cataract are uveitis, retinitis pigmentosa, essential
iris atrophy, chronic hypotony, absolute glaucoma and
high myopia14. Cataract also occurs secondary to intra­
ocular surgeries — glaucoma filtration surgery and vit-
rectomy 15. Furthermore, epidemio­logical studies24 have
demonstrated that lower socioeconomic status, lower
education level and poorer overall nutrition are associ-
ated with increased prevalence of age-related cataracts.
Exposure to sunlight and ultraviolet B (UVB) radiation
accelerate cataract development 25,26, as do smoking and
alcohol consumption27. Congenital or juvenile cataracts
are rare compared with age-related cataract; they can be
idiopathic; inherited (autosomal dominant, recessive or
X‑linked); caused by intra­uterine infections with rubella,
varicella, toxoplasmosis or herpes simplex; or associated
with various systemic dis­orders (such as galactosaemia)
or genetic syndromes (such as trisomy 21)15.
Surgical rate
Cataract surgery is performed more often in developed
regions, including North America, western Europe and
Japan, with 4,000–6,000 surgeries compared with ≤500
surgeries per 1 million people in developing regions,
such as sub-Saharan Africa 28. Exceptions to these
trends include India, which boasts high surgery rates,
and China, which has few surgeries relative to its gross
national product. Secondary cataract after cataract sur-
gery (with or without implantation of an IOL) is one
of the most common causes of visual impairment after
surgery 29. This condition is caused by clouding of the
remaining lens capsule, but can be easily treated by a
YAG (yttrium aluminium garnet)-laser capsulotomy.
Mechanisms/pathophysiology
The human crystalline lens is an encapsulated bag of
transparent sequestered proteins. Changes in the arrange-
ment and alterations in the character of the lens proteins
result first in increasing rigidity of the lens, and eventual
loss of transparency 30. The first process causes presbyopia
— the loss of natural focusing ability (a­ccommodation).
The second process leads to cataract (FIG. 2).
Changes in lens proteins
Crystallin biology. The lens is a unique organ that lacks
arterial or venous blood circulation and exhibits rela-
tively low levels of cellular metabolism. The elongated
lens fibre cells lack organelles such as nuclei, mitochon-
dria and ribosomes, and are packed with a high concen-
tration of distinctive proteins — the lens crystallins31.
The crystallins are transparent and have a high refractive
index. The lens proteins are not replaced or degraded,
and the continued transparency of the lens depends
on crystallins maintaining their native structures and
solubility throughout the human lifetime. Loss of their
native fold renders crystallins prone to aggregation into
high molecular-weight complexes, which results in cata-
ract32. In juvenile cataract, aggregation is often caused by
m­utations in the genes encoding lens proteins33.

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PRIMER

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

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 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

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PRIMER
PAX6) and NHS (Nance–Horan syndrome protein),
can also cause cataract. The diversity of identified genes
reflects the heterogeneous mechanisms and phenotypic
v­ariations evident in cataract heritability.
Notably, at least two congenital cataract genes, HSF4
(REF. 59) and EPHA2 (REF. 60) (encoding ephrin type‑A
receptor 2), also contribute to the development of age-
related cataracts through interactions with environ­
mental factors. Genotypic differences exist among
cataract subtypes: for example, the frequency of two
mutated alleles in SOD1 (superoxide dismutase 1) dif-
fer between patients with cortical cataract and patients
with either nuclear or posterior subcapsular cataract 61.
Similar differences were found in the frequency of muta-
tions in OGG1 (N‑glycosylase/DNA lyase)62. GSTM1
(gluta­thione S‑transferase mu 1) mutations increase risk
for cortical age-related cataract 63. In a Chinese study 64,
one single-nucleotide polymorphism in WRN (Werner
syndrome ATP-dependent helicase) was associated with
age-related cataract in general and another one with cor-
tical cataract specifically, and a BLM (Bloom syndrome
protein) polymorphism with nuclear cataract. Genetic
diagnosis of heritable cataract has become increas-
ingly reliable with recent technological advances. Next-
generation sequencing has identified cataract-causing
gene variants in 27 of 36 patients (75%)65. In exome
sequencing of 18 Chinese families, 12 of them (67.6%)
showed cataract mutations in 34 genes66. A recent meta-
analysis of genome-wide association studies has con-
firmed the association of polymorphisms in KCNAB1
(voltage-gated potassium channel subunit beta‑1) and
CRYAA (αA‑crystallin) with age-related nuclear cataract
in Asians67. New technologies will enable exhaustive
mapping of cataract genes, and the characterization of
gene functions should lead to a complete understand-
ing of cataractogenesis and enable the identification of
genetic markers to aid prevention.
Diagnosis, screening and prevention
Diagnosis
Cataracts are visible during clinical evaluation of the eye
(FIG. 3). Patients are evaluated for visual impairment and
other symptoms, and for concomitant eye diseases that
could influence the surgical plan or visual outcome68.
Visual impairment can be assessed subjectively accord-
ing to the patients’ perception or by visual acuity meas-
urements. Visual acuities are recorded for both far and
near distances. Assessment of the intra­ocular pressure,
a b c advances in IOL design (FIG. 4).
Nature Reviews | Disease Primers
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.
c | Mature cataracts lead to the complete opacification of the lens; the image shows a
white mature cataract.
6 | 2015 | VOLUME 1
© 2015 Macmillan Publishers Limited. All rights reserved
the lacrimal apparatus, eye alignment in the orbita,
motility and pupillary function is helpful for planning
surgery and providing a prognosis of the patient’s vis-
ual function. Slit lamp biomicroscopy is performed to
examine the eyelids, lashes, cornea, anterior chamber,
pupillary dilatation and hardness of cataract. Detailed
fundus examination through a dilated pupil can evalu-
ate the status of the lens, macula, peripheral retina, optic
nerve and vitreous humour 69. Examination of the red
fundal reflex (the reddish-orange reflection of light from
the retina) using a direct opthalmoscope lens set at +10
dioptres, at a distance of 60 cm, will enhance the areas
producing optical aberrations and thus help to diagnose
cataract. Supplement tests — for example, for contrast
sensitivity, glare disability and ocular wavefront testing
for visual aberrations — can help to identify the cause
and level of severity of visual symptoms70. Testing using
a potential acuity meter, laser interferometer or scanning
laser ophthalmoscope projects an image onto the retina
through relatively clear regions of the lens and attempts
to predict the visual acuity following cataract surgery 71.
If necessary, other ancillary tests are performed, includ-
ing colour vision or visual field measurement, optical
coherence tomography, fluorescein angio­graphy and
B‑scan ultrasonography.
Prevention
As mentioned above, age-related cataract is a multi­
factorial disease, and genetic and environmental fac-
tors contribute to cataract development 12, including
nutrition72. Epidemiological research suggests that the
risk of cataract can be diminished by adhering to diets
that contain high levels of vitamin C, lutein, zeaxanthin,
B vitamins, omega‑3 fatty acids and multivitamins and
avoiding frequent and large intakes of simple carbo­
hydrates73. In the Age-Related Eye Disease Study, intake
of a multi­vitamin supplement was moderately protec-
tive against the development of cataracts74. However,
because cataract is a degenerative disease mainly caused
by a­geing, methods of prevention are scarce.
Management
Deteriorating visual function because of cataract
requires restoration of the transparency of the optical
pathway through replacement of the clouded crystal-
line lens with an IOL with appropriate refractive power.
Current surgical techniques achieve these goals with
precision, reproducibility and safety owing to our ability
to measure the optical parameters of the eye, advanced
technologies to remove the cataract and continuing
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-
ing in the anterior capsule the large, firm lens nucleus
and softer surrounding cortex are removed. The IOL is
then placed within the vacated capsular bag, where it lies
anterior to the remaining clear posterior capsule.
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 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
developed by Charles Kelman in the late 1960s75 and
uses ultrasonic energy to vibrate a titanium needle
at high frequencies, which fragments the rigid lens
nucleus; the resulting emulsate is simultaneously aspi-
rated from the eye (FIG. 4a). The benefit of phacoemulsi­
fication over purely manual methods is the ability to
extract the large nucleus through a small incision of
≤3.0 mm. Foldable IOLs are then implanted through this
small incision, which generally can be left unsutured.
Improvements in machines and needles now enable sur-
gery through mini-incisions of 2.2 mm or micro-­incisions
of ≤1.8 mm. However, the use of micro-incisions requires
special IOLs. Small incisions have numerous advantages:
topical instead of local injection anaesthesia can be used,
e­specially if the incision is made in the peripheral cor-
nea; the surgeon enjoys better control of the intra­ocular
environment and greater safety should the patient
move; structural integrity of the incision is quickly re-
established and fewer physical restrictions are necessary
after surgery; and, finally, smaller incisions minimize
alterations of the corneal shape, which would cause
and visual rehabilitation in particular have made phaco-
emulsification the gold standard in developed countries
for more than two decades. In developing countries, cost
and other considerations drive the widespread use of
manual techniques (see below).
Although not a substitute for individual surgical skill,
advances in phacoemulsification and other surgical
techno­logies have improved the safety and reproducibil-
ity of small incision cataract surgery. This is particularly
true for the most advanced cataracts that have larger
and harder nuclei76. As with any microsurgery, improve-
ments in surgical microscopes have been important.
Furthermore, advances have been made in viscoelastics,
which are transparent viscous gels that the surgeon uses to
protect the intraocular structures from surgical trauma.
Improved viscoelastics have reduced the risk of corneal
decompensation77 (corneal oedema resulting from failure
of the corneal endothelium to keep the cornea relatively
dehydrated). Other devices such as iris retractors, pupil
expansion rings, capsule retractors and capsular tension
rings facilitate successful surgery in challenging eyes
with smaller pupils or abnormal zonules. Finally, dyes to

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PRIMER
stain and enhance visibility of the anterior capsule have
improved the success rate with mature white cataracts.
Potential benefits from automating certain surgical steps
with femtosecond laser t­echnology are being evaluated78.
Most IOLs are made of acrylic plastic or silicone that
render the lens foldable. IOL research initially focused on
developing the safest design. Further advances were made
to optimize the optical properties. Modern IOLs block
UV light, minimize unwanted optical spherical aberra-
tion and inhibit secondary opacification of the posterior
capsule79. Similarly to other corrective lenses, IOLs come
in multiple refractive powers. New IOL designs address
astigmatism (toric lenses)80 and presbyopia (multifocal
lenses)81 to reduce the need for glasses. Modern technolo-
gies and IOLs have transformed cataract surgery into one
of the most common refractive procedures.
M‑SICS and modified M‑SICS. Phacoemulsification is the
benchmark for cataract extraction in the developed world.
There are, however, a number of issues surrounding its use
in economically less-developed societies. It requires a sub-
stantial investment in the phacoemulsification equipment
and much higher recurrent costs for medical consumables
than are required by manual methods. Cost and expertise
involved in equipment maintenance is also a concern in
developing countries. Moreover, compared with manual
cataract surgery, the phacoemulsification procedure
usually takes more time and effort to learn — and the
required teaching facilities and capacities might be lack-
ing in developing countries. Finally, the manual technique
is a better choice for the hard and mature cataracts that are
more common in poor populations.
Accordingly, alternative surgical techniques have been
developed for cataract surgeries in developing countries.
The most popular technique is a sutureless M-SICS82
(FIG. 4b). Modifications of the M‑SICS technique, includ-
ing sutureless large incision manual cataract extraction
(SLIMCE)83–85, are gaining popularity, especially in
China. All of these modifications use a larger incision to
increase the safety of cataract removal and a long, suture-
less scleral tunnel incision to minimize astigmatism and
accelerate physical and visual recovery.
M‑SICS achieves excellent outcomes with lower
cost and surgical time than phacoemulsification. Aside
from speed and affordability, M‑SICS is easier for less-­
experienced surgeons to learn and, in their hands, is safer
for advanced mature cataracts. Furthermore, dropped
nuclei — a serious complication of cataract surgery that
involves nucleus dislocation onto the retina — are rare
with M‑SICS. This complication carries a poor prognosis
if it is not properly managed by a vitreoretinal special­
ist, which is a rare subspecialty in many developing
c­ountries. Both M‑SICS and phacoemulsification are safe
and provide excellent visual outcomes86.
Femtosecond laser-assisted cataract surgery. Since
phacoemulsification became the most popular cata-
ract treatment in the early 1990s, numerous alternative
methods of liquefying or softening the cataract for small
incision extraction have been investigated. In what must
be considered a truly rare occurrence in medicine, we
8 | 2015 | VOLUME 1
© 2015 Macmillan Publishers Limited. All rights reserved
use essentially the same basic technology today that
Charles Kelman first designed in the late 1960s. Early
attempts to use lasers to liquefy the lens nucleus proved
no better than ultrasonic emulsification; femtosecond
lasers now provide a way to automate certain steps of
the cataract procedure87–89 (FIG. 4c). FLACS was approved
for cataract treatment in 2010 and represents a new
frontier in cataract surgery. However, the technique is
a relatively new technology and several issues need to
be addressed, including risks of pupil constriction and
subconjunctival haemorrhage90.
Femtosecond lasers are used to perform the corneal
incision, the anterior capsular opening and partial frag-
mentation of the lens nucleus91,92. After the anaesthetized
eye is docked to the laser instrument, 3D images of the
cornea and lens are captured93. The infrared laser is then
programmed to deliver energy in extremely short pulses
to make tissue cuts that are automatically registered to
and guided by these images. Traditional phacoemulsifi-
cation is then used to emulsify and extract the lens, and
the remainder of the procedure, including IOL implanta-
tion, is performed in the usual manual manner. Lasers
are also used to make partial-depth corneal incisions to
treat astigmatism94. This technique of astigmatic kera-
totomy is o­therwise performed manually with special
diamond blades.
Such automation offers the potential to improve both
the safety and precision of surgical manoeuvres, and
many think that FLACS offers advantages for certain
complicated eyes. However, there is no robust data show-
ing that FLACS improves visual or refractive outcomes
compared with traditional phacoemulsification. Indeed,
substantial controversy surrounds FLACS because it adds
considerable expense, which usually has to be borne by
the patient. Although the notion of laser-assisted surgery
is conceptually appealing to patients, greater adoption of
this costly technology will require convincing evidence
of improved outcomes.
Prevention of endophthalmitis
Endophthalmitis is a visually devastating complication of
cataract surgery with an incidence ranging from 0.028%
to 0.345%95,96.
Use of topical antibiotics starting 1–3 days pre-
operatively has been shown to reduce conjunctival
bacterial count 97. Broad-spectrum drugs such as the
fourth-­generation fluoroquinolones are currently
being used routinely by some surgeons, but increas-
ing drug resistance to fluoroquinolones has made their
use debatable. Povidone iodine is a broad-spectrum
antiseptic with bactericidal, virucidal and fungicidal
properties, and it is applied before surgery for ocu-
lar antisepsis98,99. This prophylaxis reduces the risk of
postoperative endophthalmitis100,101.
Antibiotic prophylaxis can also be applied as a direct
intra-cameral bolus at the end of surgery. A prospective
randomized multicentre study initiated by the European
Society of Cataract & Refractive Surgeons (ESCRS)
showed that intra-cameral cefuroxime reduced the inci-
dence of postoperative endophthalmitis fivefold69,102.
Intra-cameral injection guarantees supra-threshold
www.nature.com/nrdp

antibiotic levels for an extended period of time69, and this
mode of antibiosis is superior to subconjunctival injec-
tion. No evidence suggests the use of antibiotics in irrigat-
ing infusion fluid3. Cefuroxime does not increase the risk
of allergic reactions because it does not share molecular
homology (in the side chains) with penicillin103 — an
often-used antibiotic that commonly causes allergies.
Recently, a single-unit dose of cefurox­ime designed for
intra-cameral use has been approved, which reduces the
risk of contamination and o­verdosage that can lead to
ocular toxicity 104.
Cefuroxime is a second-generation cephalosporin with
bactericidal action against many Gram-positive organ-
isms and some Gram-negative organisms. However, it
does not cover methicillin-resistant Staphylococcus aureus
(MRSA), some Enterococcus strains and Pseudomonas
spp. Vancomycin and moxifloxacin have also been used
for intracameral prophylaxis95. Vancomycin is effec-
tive against MRSA, but because it is the last drug avail-
able against many multidrug-resistant bacteria, its use as a
prophylactic antibiotic is debated. The fourth-generation
fluoroquinolones, such as moxifloxacin, have a broader
antimicrobial spectrum than cefuroxime and high
potency, but MRSA has developed resistance.
There is no universally accepted consensus on a pre-
ferred protocol for asepsis, antisepsis and antibacterial
prophylaxis. An international joint effort to produce
guidelines is much needed.
Refractive errors
Astigmatism. Simultaneous reduction or elimination
of pre-existing astigmatism during cataract surgery is a
common practice. The prevalence of astigmatic refrac-
tive errors varies from 32.3% to as high as 58.8%105. The
correction during cataract surgery is achieved through
neutral­ization of the pre-existing astigmatism by surgically
induced astigmatism106, peripheral corneal-relaxing inci-
sions107 or implantation of a toric IOL108–110. These meth-
ods can be used in isolation or combination depending on
the degree of astigmatic correction needed111. Correction
of astigmatism will contribute to a better p­ostoperative
visual outcome and lessen the need for glasses.
Presbyopia. Conventional monofocal IOLs do not pro-
vide focus at all distances. Patients with good uncorrected
distance acuity require reading glasses to focus on near
objects. Several strategies or technologies are available to
reduce the need for reading glasses after cataract surgery,
including variable-focus lenses; the use of intracorneal
inlays that enable increased depth of focus and improved
near vision in the non-dominant eye; and special IOLs.
Monovision with monofocal IOLs112,113 enables a dif-
ferent focal point to be targeted in each eye. Accordingly,
the binocular patient is able to see across a broader range
of distances compared with having the same refraction
in both eyes. A small difference is generally well toler-
ated and does not prevent binocularity; however, this
usually will not provide optimal uncorrected near focus.
Achieving a larger difference in focal points might
improve uncorrect­ed reading ability but can impede
bino­cular summation, depth perception and stereopsis.
NATURE REVIEWS | DISEASE PRIMERS
© 2015 Macmillan Publishers Limited. All rights reserved
PRIMER
Many patients find it d­ifficult to adapt to a large d­ifference
in focal points.
Multifocal IOLs114,115 have two or more separate focal
points. They have both a far and a near focal point,
which improve near vision compared with monofocal
IOLs. However, there are optical trade-offs, including
reduced contrast sensitivity, halos or other unwanted
images, and a greater reduction in overall image quality
from residual astigmatism, refractive error and IOL tilt
or decentration. In addition, the uncorrected midrange
vision might not be optimal. Nevertheless, monofocal
mono­vision and multifocal IOLs can provide high levels
of patient satisfaction116–118.
Accommodating IOLs119 have long been sought
after as the functional equivalent of the natural lens.
The concept is to have an IOL that shifts focus through
a dynamic mechanism initiated by the ciliary muscle;
however, single-­optic (containing only one optic com-
ponent) accommodating IOLs cannot achieve sufficient
levels of this type of control. Several accommodating IOL
designs are under development and in varying stages of
clinical evaluation.
Extended depth of focus IOLs are monofocal IOLs
that provide greater depth of focus through certain
design modifications, such as increasing spherical aber-
ration of the optic. This improvement in focus range
is called pseudo-accommodation because dynamic
alteration of either lens shape or position is lacking.
Several of these IOL designs are under development or
in clinical studies, and would lend themselves well to a
monovision strategy 120.
Complicated cataracts
As with any eye surgical procedure, some eyes present
challenging conditions that increase the surgical diffi-
culty and the risk of complications. Small pupils, mature
cataracts and weak zonules are the most common risk
factors for surgical complications. Fortunately, advances
in phacoemulsification technology, the develop­ment of
ancillary devices and better surgical training and experi­
ence have improved the prognosis of cataract surgery
p­erformed on challenging eyes.
Small pupil. Small pupils pose problems for cataract
surgery 121–123. The pupil is dilated with topical mydriatic
drugs for all cataract surgeries to improve the surgical
access to, and visualization of, the lens nucleus, cortex
and capsular structures. The width of pupil dilation in
response to dilating drops varies by individual. Limited
dilation poses a risk of surgical complications such as iris
trauma or tearing of the anterior or posterior capsule.
Other causes of small pupils include synechiae (restric-
tive adhesions) and use of pupil-constricting medications,
including pilocarpine and systemic α1-adrenergic receptor
antagonists (which are used, for example, to treat benign
prostatic hyperplasia)124. Small pupils can be enlarged
intraoperatively by injecting α1-adrenergic receptor ago-
nists, such as phenylephrine or adrenaline, into the eye or
by inserting mechanical devices, such as iris retractors or
pupil expansion rings, to temporarily expand the pupil
(FIG. 5a).
VOLUME 1 | 2015 | 9
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.

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© 2015 Macmillan Publishers Limited. All rights reserved


Box 2 | Intraocular lens power in childhood cataract
Various strategies have been employed to determine intraocular lens power for
cataract surgery in children. In general, the aim is to the leave the eye mildly hyperopic
at the end of surgery to counter the continued myopic drift that occurs with age, but
there is no consensus as to the ideal approach143.
One of the suggested approaches is age-based and aims for the following refractive
powers postoperatively:
• <2 years: +4 dioptre
• 2–4 years: +3 dioptre
• 4–6 years: +2 dioptre
• 6–8 years: +1 dioptre
• >8 years: ±0 dioptre (emmetropia)
However, these and other similar guidelines are rules of thumb and need to be
modified for the individual patient on the basis of their clinical situation and the
surgeon’s experience.
If the posterior capsule is left intact during cataract
surgery in children, it will become opaque in almost all
cases owing to the proliferation of epithelial cells. Initial
attempts to prevent this included the performance of a
primary posterior capsulorhexis (removal of the pos­
terior capsule; during traditional cataract surgery only
the anterior capsule is removed) and anterior vitrec-
tomy to remove the scaffold for proliferating lens cells.
To avoid removal of the vitreous in these young eyes,
which involves more invasive surgery and has more
risks than surgery without this procedure, the IOL can
be placed in the capsule and moved through the pos­
terior ca­psulorhexis into the vitreous humour 136. A more
recent approach — ‘bag‑in‑the-lens’ (BIL) — involves
an IOL with a circumferential groove into which the
remaining outer ring of the capsule, which has not been
removed, fits137. When correctly placed, the lens itself
acts as a mechanical b­arrier, which restricts the access
of proliferating lens epithelial cells and maintains a clear
visual axis137. Even if post­operative opacification develops,
anteri­or vitrectomy and s­urgical capsulotomy seem to be
safe and effective138.
IOL implantation in children younger than 1 year of
age is controversial, although some major institutions
around the world do not have an age limit for infants139,140.
The lens attains 90% of its final size by the age of 2 years,
and further growth of the eye involves the posterior seg-
ment, which makes choosing the IOL power in children
<2 years of age difficult141 (BOX 2).
Finally, even after effective cataract surgery using the
above strategies, amblyopia (‘lazy eye’ owing to impaired
vision development in childhood) remains a substantial
problem, especially in unilateral cataracts and in older
children. Hence, intense efforts to stimulate the visual
pathways of the affected eye in an effort to attain the
maximum vision possible are mandatory after surgery.
Thus, despite the many advances in the field of paediatric
cataract surgery, challenges remain, especially in children
<1 year of age139,140,142,143.
Cost-effective strategies
The costs of cataract surgery can be attributed to the fol-
lowing: training of surgeons; infrastructure and support
NATURE REVIEWS | DISEASE PRIMERS
© 2015 Macmillan Publishers Limited. All rights reserved
PRIMER
(paramedical personnel, buildings and utilities, instru-
ments and devices, and sterilization)144–146; recurring costs
(disposables and IOLs); costs for the patient to travel;
medications; glasses (if required); and costs caused by
possible complications84,147 and their management. Some
of these costs are borne by the patient (price to consumer);
the rest are the responsibility of the health-care system
(cost to provider).
The manner in which these costs are defrayed dif-
fers between developed and developing countries. In
many developed countries, insurance — either private
or through state health-care systems — covers most of
the cost. By contrast, in developing countries insurance
is often lacking and most of the cost, or often all of it,
comes out of the patient’s pocket. Fortunately, in many
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
sidized procedures using cheaper, non-foldable IOLs); for
example, in India, cataract surgery costs for patients range
from US$200 to $600 (REF. 148).
However, particularly in developing countries, many
patients have no or very limited financial resources, and
for them even the costs listed above can be prohibitive.
In India, various non-governmental agencies have estab-
lished cost-effective programmes that provide safe, effec-
tive interventions for cataract for such patients149. Most
of these programmes include outreach and screening
patients in villages; those with cataracts are then brought
to the hospital for surgery, and postoperative care is pro-
vided at their village. Cost can be reduced by maximizing
the use of available resources, including the use of reusable
materials, which are generally less costly than disposables.
Many of the centres providing such surgery also have ‘pay-
ing sections’ for patients who can afford it, and part of
this income is used to subsidize the ‘free service’ section.
However, these centres depend on skilled surgeons who
are willing to work for a cost-effective salary.
In the above model, the patient does not have to pay
at all, and the costs of the surgery are subsidized partly
from government grants, partly from voluntary dona-
tions from affluent members of society and partly from
the hospital itself. These efforts have improved access
to cataract surgery, which has resulted in a substantial
reduction in the burden of cataract blindness in India149.
Similar efforts are ongoing in other parts of the develop-
ing world as well83,150–152. Cost-effective strategies require
a more holistic perspective that takes into account socio-
cultural elements and appropriate models of health care
and delivery 153,154.
Quality of life
Cataract extraction is one of the most commonly per-
formed surgeries in the world. Successful surgeries lead to
a marked improvement of vision and quality of life155. This
applies even to eyes with concomitant eye diseases, such
as age-related macular degeneration and glaucoma, and
to patients who have already undergone cataract surgery
in their first eye156. In general, the visual improvements
from cataract surgery will benefit m­ultiple domains of life,
including emotional and social life157.
VOLUME 1 | 2015 | 11
PRIMER
Studies in populations with low income have shown
long-lasting benefits — restored sight after cataract
surgery improved health-related quality of life, well­
being, family wealth and spending power 158. Whether
and how much cataract surgery-related improvement
in vision reduces the risk of falls, hip fractures and other
major accidents remain unclear 159. Cataract surgery
improves cognitive function and psychological dis­
orders160, which suggests that delayed surgery in elderly
patients with severe cataract-related visual impairment
might lead to partial intellectual deprivation and early
cognitive dysfunction.
Outlook
Overall picture
Globally, the age-standardized prevalence of cataract
showed a marked decline between 1990 and 2010. The
number of people affected by blindness and moderate
to severe visual impairment due to cataract decreased
between 1990 and 2010 from 12.3 million to 10.8 mil-
lion, and from 44.0 million to 35.2 million, respectively 7.
In 2010, the prevalence of cataract as a cause for blind-
ness and moderate to severe visual impairment in people
≥50 years of age was 0.7% and 2.2%, respectively. This
represented a decline from 1.3% in 1990 for blindness,
and 4.4% for moderate to severe visual impairment. The
decline of cataract as a cause for blindness and vision
impairment was most marked in east Asia, tropical Latin
America and western Europe (with the age-standardized
prevalence falling by more than half in all three regions,
for both blindness and moderate to severe visual impair-
ment). The region with the smallest decline was east
sub‑Saharan Africa7.
The battle against cataract blindness is an ongoing one:
the incidence of cataract is constantly increasing owing to
ageing populations161. Despite technological and surgical
advances, much work needs to be done, and it is impera-
tive that appropriate strategies are formu­lated and imple-
mented worldwide. The goals can vary in different parts of
the world. In the developed world, the focus is on restor-
ing unaided visual acuity and a return to work as early as
possible. This has prompted the develop­ment of techno­
logies such as aspheric, multifocal and accommodating
IOLs, torsional-mode phacoemulsi­fication and FLACS.
Cost is not the primary concern for these technologies.
By contrast, in the developing world the focus is on safe,
reproducible cataract surgery, and cost is of paramount
importance. Also, surgery has to overcome many barri-
ers, including poor patient education, social and cultural
customs that prevent the patient from accessing health
care, varied geographical conditions that affect the access
to health care, and a skewed distribution of resources, with
poor availability of quality services in the rural regions153.
Technologies to stay
Current methods of cataract surgery include M‑SICS,
phacoemulsification and FLACS. Although the precision
of cataract surgery improves with the advent of newer
technologies, so does the cost 154. Surgeons and patients
welcome improvements in precision, especially those
that increase the safety of a surgical procedure. However,
12 | 2015 | VOLUME 1
© 2015 Macmillan Publishers Limited. All rights reserved
technological improvements must always be balanced
with cost to the patient and the health-care system. The
shift from a sutured extracapsular approach to phaco-
emulsification was a major advance and resulted in sub-
stantial patient benefits162. However, the steep increase
in costs prompted the development of a manual small
incision procedure, and this is now commonly per-
formed in developing countries, with excellent results.
The introduction of FLACS does not provide the same
major step in improvement of outcomes as the previous
example. However, FLACS has its proponents who think
that the increased precision is an advantage. Clearly, at
the present time, FLACS is not the preferred approach
in the developing world.
New refractive IOL technologies
Owing to several decades of improvements and advances
in design, the IOL is the most commonly implanted
device in all of medicine. The term ‘medical miracle’ is
overused, but a relatively inexpensive device that can
be folded and implanted through a micro-incision, that
never needs replacement, that is permanently held in
place by natural ocular structures, that provides visual
clarity identical to that of a child and that can correct
refractive error is just such a miracle to the blind patients
whose vision it restores.
Young healthy crystalline lenses have the ability to
accommodate and vary focus, and the development of
IOLs that can mimic this behaviour is the ultimate goal.
Two IOLs in varying stages of development and clini-
cal trial exemplify the ongoing innovative approaches to
IOL technology 163. One of these novel approaches uses
lenses with liquid optics to provide accommodation in
response to ciliary muscle contraction164–166. Small fluid
shifts of a silicone gel change the refractive curvature of
the lens to generate a dynamic shift towards near focus.
However, although these IOLs show promise, they have
yet to be validated in large clinical trials and are best
considered experimental at the present time.
IOLs come in multiple powers, and the surgeon
attempts to calculate and select the IOL power pre­
operatively that will produce the desired refractive out-
come. Variables such as astigmatism induced by the
incision or variation in the final axial location of the IOL
mean that the precise desired outcome is never assured.
Accordingly, the ability to change the IOL power post­
operatively, after the patient’s refraction has stabilized,
would be a very exciting prospect. Such non-invasive
adjustments would enable the ophthalmologist to cor-
rect any residual refractive error, such as astigmatism
or myopia. An approach to achieve this that is cur-
rently being investi­gated is a light-adjustable monofocal
lens, which consists of a partially polymerized material
that can be crosslinked with UV light after implanta-
tion to change the lens shape and p­rovide the desired
refractive adjustment167.
New preventive strategies
The incidence of cataracts and the number of cataract sur-
geries are increasing, but currently no validated therapies
or nutritional interventions exist that can prevent or slow
www.nature.com/nrdp
 PRIMER

cataract development. Cataract prevention might help to Summary

reduce the social and economic burden of the disease.
Commonly known antioxidants, such as vitamins A, C
and E and carotenoids, as well as antioxidative and anti-
inflammatory phytochemicals might prevent or delay the
progression of cataract by scavenging free radicals and
upregulating glutathione expression168. Phytochemicals
that could be used as nutritional supplements for cata-
ract prevention include flavonoids (found in green tea,
cat­echins, Ginkgo biloba and grape seed extract), antho­
cyanins (found in bilberries and blueberries), and stil-
benes (for example, resveratrol)169,170. Recent studies
have shown that herbal molecules, including curcumin
and epi­gallactocatechin‑3‑gallate, can inhibit amyloid
formation and effectively disaggregate amyloid fibres171
and might prevent crystallin aggregation. Furthermore,
chemi­cal chaperones, such as sodium 4‑phenylbutyrate
and trimethylamine N‑oxide, which have been shown
to make truncated human γD‑crystallin soluble in cell
culture172, could also be anti-cataract agents. These small
molecules can inhibit protein aggregation, stabilize
unfolded mutant crystallin and rescue insoluble trun-
cated crystallin, s­uggesting that they act on the protein
unfolding pathway.
The success of modern cataract surgery is the result of a
long and exciting process. Few other medical procedures
have benefited as much from innovations in surgical
and implantable technology. Because of the enormous
prevalence of cataract, few other medical procedures
have enhanced the lives of so many patients. Improved
safety, prognosis and outcomes have enabled surgery to
be performed at increasingly earlier stages of cataract.
However, ageing population demographics will esca-
late the financial burden that is placed on almost every
society to provide treatment for cataract. Currently, the
biggest challenge is to curtail and reduce cataract blind-
ness in the developing world, where cataract accounts
for more than half of all blindness.
In the developed world, the refractive benefits of IOL
implantation have made cataract surgery one of the most
common refractive procedures in ophthalmology. With
further IOL advances, increasing numbers of patients
might opt to pay for surgery before developing a cata-
ract that affects their vision substantially. This enables
many patients to also become independent of glasses,
and it reduces the overall economic burden of cataracts
on society.

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Acknowledgements
The authors express their gratitude to E. X. Y. Liang for her
contributions to technical editing and refining references.
Author contributions
Introduction (S.K.R., V.R., D.L. and D.F.C.); Epidemiology
(P.M. and J.J.); Mechanisms/pathophysiology (J.K., C.P.P. and
V.R.); Diagnosis, screening and prevention (Y.L. and V.R.);
Management (S.K.R., D.F.C., D.L., Y.L., V.R. and M.T.); Quality
of life (J.J. and V.R.); Outlook (S.K.R., J.J., D.F.C., V.R., J.K.
and D.L.); overview of Primer (D.L.).
Competing interests statement
M.T. holds a patent on the BIL and ring caliper licensed to
Morcher (Germany), which results in royalties. D.F.C. is a
c­onsultant for AMO, Calhoun Vision, Power Vision and LensAR.
All other authors declare no competing financial interests.
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