Background
Information:

Cataract is defined as the
opacification (or clouding) of the crystalline lens of the eye (Olson et al. 2017). The crystalline lens inside
the eye is a key optical component, responsible for delivering accurately
focussed light onto the retina at the back of the eye.  Cataract is the second leading cause of
blindness in western Europe but the leading cause of blindness in the
developing world and both central and eastern Europe (Bourne et al. 2013). However, cataracts can be
successfully treated with extraction of the crystalline lens and replacement
with an intra-ocular lens (IOL) implant. 
Cataract extraction is the most common surgery in the UK (330,000 per
year (Day et al. 2015) and Europe (Eurostat
2016).
As cataract is predominantly an age-related condition, all individuals that
live long enough will develop some degree of cataract throughout their
lifetime. It is projected that by 2039, one in 12 people in the UK will be over
the age of 80 years and thus, increase the demand on cataract services (Office for National Statistics GB 2014). Due to this ageing
population profile across the UK (and Europe), it has never been more important to create a
more efficient and cost-effective model of cataract patient care.

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A cataract may form due to
nutritional, genetic, metabolic or environmental conditions (Fong 2008). They may also form secondary to other
ocular/systemic diseases or ocular trauma. However, the most common cause of
cataract is age (Fong 2008),
and there are three main types of age-related cataract. These are; cortical,
nuclear and posterior sub-capsular. Each cataract differs based on its
location in the crystalline lens (Fong 2008), and there can be more than one
type simultaneously.

 

 

Cortical cataract is the
most common form of lens opacity. As the cataract develops, the radical spokes
are formed in the periphery of the lens (Salmon and Bowling 2015) which can be seen above
in figure 1. It is not until the spokes start to encroach on the visual axis or
the pupillary region that vision will be affected (Hurst
1993).

The next most common is a
nuclear cataract. This is often described as the yellowing of the crystalline
lens (Fong 2008). This yellowing effect is
caused by the deposition of urochrome pigment (Salmon
and Bowling 2015). As the cataract develops, the
nucleus changes from being optically invisible to optically visible. This is
usually seen from the age of 50-60 years old (Young
1993).

Posterior sub-capsular
cataracts are the least common of the three. This cataract is usually located
centrally in the pupil in the posterior cortex (Young 1993). It is often
described as the most symptomatic (Cleary and Barsam 2016), due to its location in
the eye (Salmon and Bowling 2015).

Cataracts are generally
first noticed by a clinician on routine eye examinations prior to the patient
being aware of any symptoms or a reduction in vision (Peate et al.
2014).
Various grading systems can be used for the classification of cataract severity
such as the Lens Opacification System III (LOCS-III) and the Oxford Clinical Cataract Classification
and Grading System (Frampton et al.
2014).
LOCS-III is used to grade the three major types of cataract; however, grading
scales are rarely used by practitioners when examining cataract, with visual
functional measures and patient symptoms being more important for management
and determination of readiness for surgical treatment (Royal College of Ophthalmologists, 2015). Patient reported outcome
measures are another technique used to assess a patient’s perception of their
cataract for example the Catquest-9SF questionnaire (Lundström and Pesudovs, 2009).

The cataract journey for a
patient will generally begin by a referral from their own General Practitioner
(GP) or Optometrist. The patient will be given an appointment date for their
first pre-operative cataract assessment. This normally begins with a detailed
case history which will usually be done by an ophthalmic nurse or health-care assistant.
The patient is typically transferred to a different room with a different
member of staff to have pre-operative visual checks performed, this being
proceeded by a detailed ocular examination by an Ophthalmologist in another
clinic  (this possibly occurring on a
different visit). Depending on the hospital or clinic the patient may have to
see numerous staff members and visit different rooms to use the required
instruments on their pre-operative cataract journey.

Currently, these
procedures are performed in an inefficient manner with the patient having to
move to different clinical areas to access often large instruments that are
costly to both purchase and maintain. Such an inefficient patient pathway has
been identified as a factor that can markedly increase the cost of outpatient
appointments, extend waiting times, and crucially lead to a reduction in
patient satisfaction (McMullen et al.
2014).

Biometry

Biometry is a method used to
measure both the power of the cornea and the axial length of the eye. These
measurements are of vital importance when calculating the required power of the
intra-ocular lens implant. The power of the eye is a combined power of the
cornea, the crystalline lens and the length of the eye (Astbury
and Ramamurthy 2006). At minimum, the axial length and corneal
curvature of the eye are required to calculate the power of the lens implant (Park 2007). Biometry measurements must
be accurate as a 0.3 mm error in axial length can cause a 1.00 D discrepancy in
the IOL power (Park 2007).

Currently the IOLMaster (Carl-Zeiss, USA) is the
reference-standard means by which these biometric measurements are taken and
further IOL calculations performed (Akman et al. 2016) such as the Hoffer-Q formula. This is
a non-contact instrument which uses light waves to detect the optical
boundaries of the eye and calculate their depth. In the case of a dense
cataract, the accuracy of the measurements taken by the IOLMaster are affected (Freeman
and Pesudovs 2005).
Further, in some cases, inaccuracy in biometric measures lead to poor visual
outcomes post-surgery; this is informally called ‘refractive surprise’.  The
Royal College of Ophthalmologists Cataract Surgery Guidelines state ‘what
matters most in biometry is achieving excellent results’ (Royal College of Ophthalmologists, 2015). Work by Huang and colleagues (J. Huang et al. 2013) has established the possibility that
OCT offers a superior method for ocular biometry measurements.

               

                               

 

OCT

Optical Coherence Tomography (OCT) was first
introduced in 1991 (D. Huang et al. 1991). OCT is analogous to
ultrasound with the exception that light of specified wavelength(s) rather than
sound is used to produce thousands of scans every second to produce a detailed cross-section of
the eye. This harnesses the different reflective properties of different parts
of the eye to produce a pictorial representation cross section of the eye.PJM1   When
the OCT was first introduced to the ophthalmic field, it could be used to
obtain in-vivo cross-sectional images of the anterior segment (Izatt et al. 1994), and the optic disc and
retinal layers (Hee et al. 1995) to investigate retinal
diseases such as macular oedema (Puliafito et al. 1995). 

There are three main types of OCT; Time Domain OCT, Spectral
OCT and Swept-Source OCT. The first clinical version of OCT had a maximum
scanning speed of 400 axial scans due to the physical constraints caused by the
moving reference mirror. Time Domain OCT requires the location of the reference
mirror to be changed to allow backscattered tissue intensity levels to be
detected from different depths of the tissue sample (Gabriele et al. 2011). Time Domain OCT is one of the early
designs of OCT and since then many improvements have been made to the
resolution and speed of acquisition of images. Unlike Time Domain, there
is no requirement to move the reference arm for Spectral Domain OCT to achieve
A-Scans (De Boer et al. 2003). SD-OCT can take up to 312,500 A-scans/s (Potsaid
et al. 2008) while SS-OCT can take up to 249,000
A-Scans/s (Srinivasan et al. 2008). Most instruments prior to this could take a
maximum of 27,00 A-scans/s (Gabriele
et al. 2011)

OCT has become increasingly
popular with both optometrists and ophthalmologists. It is thought that
approximately 30 million OCT scans are carried out worldwide every year making
it much more popular than all other ophthalmic imaging combined (Optical Coherence Tomography News 2014). Out of all instruments that
have been introduced within the Ophthalmic field over the past number of years,
the OCT has had the largest clinical impact (D. Huang et al. 1991). While retinal imaging has been the focus of
OCT development for use in clinical and research settings in the past, there is
growing interest in the utility of anterior segment imaging with OCT (Ramos et al. 2009; Ramos et al. 2009; Su et al.
2015; Ruggeri et al. 2016; Ruggeri et al. 2016; Martinez-Enriquez et al. 2017; Martinez-Enriquez et al. 2017).

In clinical practice, the slit-lamp biomicroscope
is the most common instrument used for the examination of the anterior segment (Gellrich 2015) and it can be seen in figure 3. However,
some aspects of the eye examination (e.g. anterior chamber angle assessment) with
the slit-lamp biomicroscope can only be performed by using additional contact
lenses (Konstantopoulos et al. 2007). Over the past number of years, more
advanced instruments such as the Pentacam-Scheimpflug (Oculus Pentacam),
Visante OCT (Carl-Zeiss
Meditec) and Slit-Lamp OCT
(Topcon) have been used to image the anterior segment (Konstantopoulos et al. 2007).

 

 

 

 

 

 

Binocular-OCT

Binocular-OCT, incorporating ‘swept-source’
laser technology is capable of non-invasively imaging the whole-eye in a
potentially small, inexpensive and portable device (Walsh 2011). Uniquely, the binocular OCT is also
capable of capturing images from both eyes in the same session without the need
for assistance from a trained technician. Through the incorporation of advanced
display and response capture systems, it is also possible to present
quantitative vision tests. Through such advanced imaging and ocular assessment
tools the Binocular-OCT has the capability to perform the functions of many
clinical tools in a single instrument. A prototype device has also recently
been shown to be easy and acceptable to patients while providing clinically
meaningful results (Chopra et al. 2017).

The Binocular-OCT has many new
and original features. It is designed with the intention of both eyes being
used together without requiring any additional assistance. OCT imaging is rapid
and is well tolerated by both children and adults. The Binocular-OCT can be
used to carry out a range of diagnostic examinations, it is not just refined to
imaging the anterior segment and fundus. Anterior segment imaging with the OCT can be used
in the examination of cataract both pre-operatively and post-operatively.

The automated whole-eye imaging
and visual function measurement capabilities of the binocular-OCT has the
potential to: (I) improve the efficiency of the patient pathway in NHS cataract
assessment clinics as the majority of clinical assessments may be undertaken in
a single instrument, (II) reduce costs due the need for fewer clinical
instruments and automated patient scan protocols, (III) enable objective,
quantitative assessment of lens opacities, (IV) offer a full suite of biometric
assessments for the calculation of IOL power, (V) facilitate rapid
post-operative assessment (e.g., macular OCT)

 

Project:

In this PhD project, the proposed
advantages of a binocular OCT system will be assessed for the assessment and management
of cataract. This research is important, to not only improve cataract assessment
and optomise surgical outcomes, but it is also vital to establish sensitive
measures of cataract density and form that may serve as more sensitive
endpoints in clinical trials.

There are five research objectives
associated with this study:

1)     
To investigate objective
quantified cataract density and localisation analysis with the binocular-OCT
compared with SL grading (LOCSIII) and lens densitometry

2)     
To correlate functional
measures of vision with (i) cataract density and localisation metrics and (ii)
patient-perceived visual disability, quantified using validated questionnaires
(CatPROM and Catquest-9SF)

3)     
To develop computational
analysis enabling measurements of axial length, anterior chamber depth (ACD),
white to white, lens curvature and thickness, and corneal curvature
measurements with binocular-OCT, and compare with established ocular biometry
measurement techniques.

4)     
To compare with calculated IOL
power through analysis of OCT measurements with current protocols in
pre-operative assessment of cataract and post-operative outcomes

5)     
To investigate surgical
outcomes in terms of (i) refractive success and the choice and position of the
IOL, (ii) patient reported outcomes using validated questionnaires (iii) vitreo-retinal
status and thickness as an indication of inflammatory response, and (iv)
straylight and flare measures.

Method:

200 patients will be recruited from
outpatient cataract clinics at Moorfields Eye Hospital (MEH) and will be
invited to participate in the research study. There are four main stages:

Stage One: The
Binocular-OCT will be used to obtain OCT images of the crystalline lens of all
200 patients. An algorithm will then be used to segment, localise and quantify
lens opacities from the OCT images. Slit lamp photography and lens densitometry
will also be performed. The OCT cataract analysis will be compared with conventional
clinical grading (LOCSIII) and Pentacam densiometry value. Three experienced
clinicians associated with the project will subjectively grade the degree of
lens opacity in each slit lamp photograph (from part 1) using the LOCS III
scale.

Stage Two: All
patients will have conventional measures of visual function performed and
automated high contrast VA measurements using the binocular-OCT. Patient
perceived visual impairment and quality of life will be assessed using
validated questionnaires such as CatPROM and/or CatQUEST-9SF.

Stage Three: Biometric
measurements including anterior corneal curvature will be undertaken using the
IOL-Master. Biometric measurements will also be calculated from Binocular-OCT
scans. IOL powers will be calculated based upon the data collected from both
the IOL Master and binocular-OCT using existing IOL-formulae (e.g. Hoffer-Q).

Stage Four: A subset
of fifty patients from the original 200 patients who have undergone cataract
surgery will be invited to return for further study measurements. These will
include (i) a binocular-OCT scan, (ii) anterior segment imagingPJM2  , (iii) subjective refraction and
conventional high-contrast VA, (iv) laser flare meter for quantification of
ocular inflammation (v) patient perceived visual impairment following cataract
extraction (Catquest-9SF and CatPROM), and (vi) C-Quant intraocular light
scatter measurements. These will be undertaken 4 weeks (+/- 1 week) following
surgery.

 

Progress to Date:

Since the beginning of October, I
have made significant progress on my PhD journey. A detailed breakdown of my
progress so far and what I still have to do can be seen by referring to my
Gannt chart on the next page. I have completed many training sessions and
workshops and a copy of some certificates can be seen in my appendices. I have
completed the 1st draft of my literature review, I am in the
progress of my ethics application and I am planning on moving to London in
early 2018 to be near my data collection site in Moorfields Eye Hospital
(honorary contract successfully gained December 2017). I have also become a
member of the College of Optometrists, Association of Optometrists and I am
also GOC registered.

 

 

Author