Cataract
Cataract is the leading cause of blindness worldwide, accounting for more than 20
million of the world population, a figure estimated to reach 40 million by 2020
(1). The removal of cataract is the most common surgical procedure performed in
those over the age of 65 in New Zealand (2).
The Department of Ophthalmology at the University of Auckland has established major
research projects involving the clinical and scientific aspects of cataract formation.
Clincal research
Currently in ophthalmic clinical practice, the classification of cataract primarily
involves a subjective clinical grading. Classification schemes for grading lens
opacities include the Lens Opacities Classification Scheme (LOCS III) and the Oxford
Clinical Cataract Classification and Grading System (OCCGS); however, these are
mainly reserved for research purposes. We are presently investigating the use of
novel techniques for additional pre-operative assessment of cataracts and postoperative
outcomes of cataract surgery and its application to the clinical setting.
Scheimpflug photography
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Figure 1. Scheimpflug slit photograph (A) and retroillumination image (B) illustrating
a dense posterior subcapsular opacity.
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Figure 2. Biometric analysis performed by the Scheimpflug camera on a normal eye.
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The Anterior Eye Segment Analysis System (NIDEK EAS-1000, Japan) is an imaging technique
based on the Scheimpflug principle that is relatively new to New Zealand and is
used for assessing lens abnormalities such as cataract. This is an accurate, reproducible
and observer-independent system that can be used to classify cataract. Scheimpflug
photography has been in use over the past decade as a non-invasive tool for in vivo
examination of the lens, however this has been a technique mainly limited to research
centres (3). It captures several types of images, including single photographic
slit sections of the anterior segment (Fig 1a) and retroillumination images of the
lens, (Fig 1b) and can be used as a postoperative imaging tool to calculate the
position of an intraocular lens implant. A unique feature of this imaging technique
is the ability to create a three-dimensional reconstruction of a lens by capturing
several static slit images (eg. Sixty images at three-degree intervals around a
central axis), providing sufficient information to determine the volume of opacity
of the lens and the exact location of the opacity (4).
Analytical functions of The Anterior Eye Segment Analysis System of these slit images
include linear densitometry of lens opacity, integral density of the lens and biometry
(see fig 2).
Wavefront aberrometry
A recent introduction to the ophthalmic clinical world is wavefront aberrometry
(5). This is a novel technique for quantifying the aberrations produced by the eye
as a whole optical system. It assesses the higher order aberrations (ie. Aberrations
beyond defocus and astigmatism) emanating from a human eye, practice that is not
routine in clinical ophthalmology (fig 3). Wavefront aberrometry has been utilised
to refine corneal refractive surgery and has recently been adapted to quantify and
analyse the aberrations induced by cataract (6). The use of this technology in assessing
patients with cataract could provide a possible explanation for patients with visual
symptoms such as glare and night driving difficulties and a relatively good high-contrast
Snellen visual acuity
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Figure 3. Table indicating each order of aberration.
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The combination of Scheimpflug photography and wavefront aberrometry in the assessment
of cataract will allow the correlation of the type of cataract with the higher order
aberrations induced by each type of cataract. This will be particularly useful in
patients with posterior subcapsular lens opacities where symptoms are dependent
on level of illumination and pupil size. A recently conducted study of twenty patients
presenting with cataract to Auckland Public Hospital reveals different wavefront
aberrometry patterns with different types of lens opacities. Nuclear opacification
induces a higher amount of negative spherical-like aberration (fourth order aberration),
whereas cortical lens opacities induce a high amount of coma (Figure 4).
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Figure 4a. Colour coded map from the Zywave Hartmann-Shack aberrometer of a patient
with predominantly cortical lens opacification. The left map shows the total aberrations
emanating from this eye; the right map illustrates the higher order wavefront from
this eye showing a high amount of coma.
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Figure 4b. Three-dimensional representation of a wavefront with predominantly coma
(left) and one with predominantly negative spherical-like aberration (right).
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Scientific research -
protein composition of lenticular opacities
The recent sequencing of the human genome has introduced a new chapter into the
analysis of the protein structure of the lens. To date, the study of protein expression
(proteomics) of the lens has concentrated on crystallins and has been done predominantly
in animal models with induced lens opacities (7,8). The major limiting factor in
the study of proteomics in human cataract formation is the availability of tissue
for research. We hypothesised that since cataract surgery is the most common procedure
performed in people over the age of 65 in New Zealand, the discarded debris from
this surgery could potentially be a prolific source of research material available
to study the protein structure of human lens opacities. Currently, the most common
surgical technique to remove cataract is phacoemulsification. This uses ultrasound
to emulsify the cataractous lens in-situ followed by aspiration of the lens fragments
and cellular debris, leaving an intact capsular bag into which a synthetic intra
ocular lens (IOL) implant is placed. In order to assure that this source of material
is of sufficient integrity to identify the molecular changes in protein expression
that are associated with the development of age-related cataract in humans, it was
first necessary to determine whether phacoemulsification induces any protein degradation.
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Figure 5. Bovine lens proteins prepared by three separate methods, Phacoemulsification
(P), Aspiration (A) and Homogenisation (H) were separated by molecular weight prior
to individual protein identification by specific antibodies. Analysis of five membrane
proteins and the intra-cellular protein actin revealed no significant differences
in protein integrity between the three separate isolation methods.
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In order to test this hypothesis, normal bovine lenses were obtained. These lenses
were extracted using three different methods. One group were emulsified by phacoemulsification,
one group were aspirated (without phacoemulsification) and one group of lenses were
dissected intact from the eye and then homogenised according to standard laboratory
techniques for protein preservation. All groups were processed using 1-Dimensional
gel electrophoresis, a technique commonly used in laboratory science for separating
proteins by their molecular weight. Six proteins were targeted in each group using
specific antibodies; five to known membrane proteins (Glucose Transporter 1, Connexin
46, Connexin 50, Chloride Channel 2, Sodium Glucose Transporter 2) and one to an
intracellular protein (actin). As shown in figure 5 all three methods of extraction
resulted in almost identical gel maps identifying the same protein with no evidence
of any degradation of proteins. Thus, we conclude that phacoemulsification does
not induce any degradation of lens proteins and therefore provides us with a abundant
source of human lens material, enabling the study of the proteomics of human cataractous
lenses which is now in progression in collaboration with Dr Paul Donaldson and Dr
Rachelle Merriman-Smith in the Department of Physiology at the University of Auckland.
Conclusion
The development of these research tools provides a new avenue for cataract research.
The combination of the classification of a subject's cataract by Scheimpflug photography
with the wavefront aberrations induced by each cataract will ascertain whether certain
types of cataract are associated with specific wavefront abnormalities. The assessment
of the molecular changes of different types of cataract will allow the correlation
of specific changes in gene and protein expression with each type of cataract.
References
- Brian G, Taylor HR. Cataract blindness - challenges for the 21st century. Bulletin
of the World Health Organization. 2001; 79(3):249-256
- Riley AF, Grupcheva CN, Malik TY et al. The Auckland Cataract study: demographic,
corneal topographic and ocular biometric parameters. Clin Exp Ophthalmol 2001; 29:381-386
- Sasaki K, Sakamoto Y, Shibata T et al. The Multi-Purpose Camera: A New Anterior
Eye Segment Analysis System. Ophthal Res 1990; 22(S1):3-8
- Masters BR. Three-dimensional microscopic tomographic imaging of the cataract in
a human lens in vivo. Optics Express 1998; 3(1): 332-338
- Sachdev N, Cairns G, McGhee CNJ. . An introduction to wavefront aberrometry of the
eye. NZ Optics May 2002, 12
- Kuroda T, Fujikado T, Maeda N et al. Wavefront analysis in eyes with nuclear or
cortical cataract. Am J Ophthalmol 2002; 134:1-9
- Lampki KJ, Shih M, Ueda Y, Shearer TR, David LL. Lens proteomics: analysis of rat
crystallin sequences and two-dimensional electrophoresis map. Invest Ophth Vis Sci
2002; 43(1): 216-224
- 8. Ueda Y, Duncan MK, David LL. Lens proteomics: the accumulation of crystallin
modifications in the mouse lens with age. Invest Ophth Vis Sci 2002; 43(1): 205-215
Download a cataract research article which originally appeared in NZ Optics(198.8KB PDF)
