Improved post-operative vision using advanced optical measurement techniques

Cataract (clouding of the lens of the eye) is primarily a problem of aging; more than half of the over 65s have some degree of cataract, and cataract surgery is one of the most frequently performed operations in the UK, helping over a quarter of a million patients per year. For the vast majority, after removal of the cataractous lens, an artificial lens must be implanted to achieve good vision. The refractive power of this lens, chosen to minimize blurring at the retina, is calculated from preoperative measurements of the refractive elements of the eye, including the dimensions of the cornea, aqueous humour, lens and vitreous humour, and the curvatures at the interfaces between element.
For well over a century, 'schematic eyes', or mathematical models, have been used to assess the overall optical refraction of the human eye, using assumed refractive index values for each element. The models have been refined over the years, as better information on the various required parameters has become available, and are still used today. The 21st century has seen the development of new methods for ocular measurements, in particular the application of optical coherence tomography (OCT), a low-power, non-laser, non-invasive imaging technique, to in vivo measurement of optical path length. However the very precision of the technique calls into question the standard RI values used in calculating IOL powers from schematic eyes. The quality of distance vision resulting from artificial lenses, post-surgery, is generally good, but further improvement can often be obtained by the use of spectacles, particularly for long-sighted and short-sighted patients, suggesting that assumed refractive index values are sometimes wanting.

The aim of the proposed research is to allow measurement of the refractive index, in vivo, for each separate element within the eye. This will enable a more accurate calculation of the correct artificial lens power to be made for an individual cataract patient, reducing, or even avoiding altogether, the post-surgery necessity of spectacles for distance vision. Given the incidence of cataract worldwide, the benefits, in terms of cost-savings and convenience to cataract patients following surgery, would be extremely widespread.
OCT is a very high resolution technique, providing detailed images of structures inside the eye, down to individual cones, only a few micrometres across, within the retina. Depth within the image always appears, however, as the product of physical distance and group index; a quantity related to, but not identical to, refractive index. The two parameters cannot be separated. To obtain the group index, and hence the refractive index, an independent measurement of physical distance is required, provided, in the proposed work, by another optical technique known as confocal imaging, in which a pinhole is positioned such that only light from a certain depth within the sample can pass through the pinhole to reach the detector.
Difficulties to be overcome in developing this technique include: (a) the generation of beams with a sufficiently small focused spot diameter and depth of field to define the location of a tissue boundary within an image to about 1 micrometre, (b) elimination of image artefacts caused by motion of the eye, relative to the instrument, during signal acquisition, and (c) the correction of image aberrations resulting in blurring of the focused light spot and hence reducing measurement resolution, (d) adjustment of the measuring instrument to remain centred on, and perpendicular to, the apex of the cornea during acquisition of a dataset.
Methods have been considered to address all these problems, and it is anticipated that the final version of the resulting instrument will be able to measure refractive index with accuracy and precision in the third decimal place, a major advance over the current lack of techniques for in vivo measurement of this important parameter.

This is a proposal driven by a clear and widespread clinical need, requesting funds to develop a technique for the remote measurement of refractive index values inside the eye. A 2001 World Health Organisation report points out that, as the population ages, cataract-induced visual dysfunction and blindness is on the increase. This is a significant global problem. In the developed world, where access to cataract treatment is rarely a problem, the emphasis is on improving the quality of post-operative vision. Benefits for cataract surgery patients are very plain; current practice results in visual acuity that is good, post-surgery, but often benefits further from the use of spectacles. Data for the refractive index of individual elements of the eye would improve the results of the modelling used to select artificial replacement lenses, resulting in improved vision post-surgery for many patients, with reduction, or even elimination, of spectacle use for distance vision. The health benefits, in terms of improved quality of life, will therefore be widespread in the UK, and indeed the wider world. Given the high prevalence of cataract in people over 50, a fully successful outcome to this project could ultimately have beneficial effects for 5-10% of an aging world population.

The ultimate goal is integration of the resulting technology into a commercial device for the ophthalmological instrument market, benefiting research communities, instrument manufacturers and health practitioners caring for the public in the UK and abroad. The world market for optical coherence tomography (OCT) equipment is robust and growing; the aim of the current project is to demonstrate that the proposed technology can be successfully implemented, ex vivo, but work will proceed with a constant awareness of the "next step" requirement to establish partnerships that will help promote, and fund, future integration into in vivo instruments, prompted by demonstrations of the prototype technology to instrument manufacturers such as Zeiss, Topcon, Canon and Shin-Nippon. Protection of any IP arising will be a priority (via our Technology Transfer facility, Cranfield Ventures, in partnership with ISIS Enterprise), followed by publication in the open literature. Our department has a strong track record of engagement with industry, including directly-funded research projects and partnerships managed under programmes run by the EU and the Technology Strategy Board, UK. We have worked with small and large UK companies (e.g. Oxford Instruments, Casella Cel) and multinationals (e.g. Procter and Gamble, Airbus, EADS) on projects resulting in new or improved commercial products. Industrial engagement, seeking technology transfer through follow-on funding opportunities, will be a key task throughout the duration of the grant.
In recent years, the impact of OCT in clinical environments, particularly in the field of ophthalmology, has been very strong. Commercial OCT instruments are now housed in numerous research hospitals worldwide, and are becoming established in high-street opticians. Even among practices that do not yet have the technology, there is an awareness of its capabilities. It is realistic in this climate to suppose that significant commercialisation, and acceptance, of the new technology could take place within a 5-10 year span.

Additional benefits include the training and personal development of the staff and research student (funded by the department), in disciplines with strong commercial applications. All staff and students leaving our department are successful in obtaining suitable employment, many of them in industrial companies. Medical imaging, and OCT in particular, is a strong and growing area commercially, offering good employment prospects in research or industry for experienced staff. Workers on the project will also gain experience in transferable skills including project management, oral and written reporting and commercial awareness.