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R&D on Ageing: developing new technologies

SUSANA MARCOS

Instituto de Óptica “Daza de Valdés”, Spanish National Research Council (CSIC)

Ocular ageing: improving the quality of sight for cataract and presbyopia sufferers

The progressive ageing of the population and rising life expectancy in developed countries will increase the number of people suffering from presbyopia and cataracts. Research into the mechanisms of accommodation and ageing of the lens is the key to improving their quality of sight.

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90% of the information the brain processes is visual. Thus, good quality of vision is a prerequisite for a good quality of life. However, sight starts suffering the effects of ageing quite early. Between the ages of 40 and 45 the eye’s ability to adapt to focus on distant and near objects starts to decline (a condition known as presbyopia). Presbyopia can have an impact on everyday tasks early in life, while the individual is HIGHLIGHTSProfile: Susana Marcos
still of working age, in a world in which we are ever more dependent on being able to perform close up tasks (such as reading from the screen of a PDA or mobile telephone, following a satellite navigation device while driving, etc.). Later in life, the development of cataracts causes severe deterioration in the quality of sight as it turns the crystalline lens opaque. The lens inevitably has to be replaced with an intraocular implant. To meet patients’ expectations today, the most up-to-date techniques are able to go beyond restoring transparency to the intraocular medium. Cataract surgery is now also aimed at correcting the refractive errors of the eye (removing the need for glasses for distance vision) and ultimately, to restore to the ageing eye the visual acuity it had in its youth, by emulating, as far as possible, the young lens.


Imagen de un ojo sano

Image of a healthy eye. / Photo: Stock.XCHNG (Sergio Ramírez)



Ageing of the crystalline lens
The cornea and crystalline lens are both lenses that project visual information about the outside world on to the retina. In the human eye the crystalline lens is approximately 4mm thick and 10mm in diameter. It is extremely complex, having a structure with an index gradient “Presbyopia can have an impact on everyday tasks early in life, while the individual is still of working age”(i.e. its refractive index is not constant, but varies from the centre towards the edges) enabling it to increase its optical power, reduce light losses caused by reflection from its surfaces, and optimise optical quality. Interestingly, in the young eye, the imperfections (spherical aberration) of the cornea are partially compensated for by the aberrations of the lens (the spherical aberration of which tends to be negative), in a similar way to the optical design of camera lenses that optimise optical quality by combining simple lenses with greater aberrations than the device as a whole. Moreover, in a young eye the lens is able to change the shape of its surfaces to focus on near and distant objects (an ability known as “accommodation”).

The lens of the eye is attached to the ciliary muscle through the ciliary body and the ciliary zonules around the lens’s equator. An accommodative stimulus causes the ciliary muscle to contract, the ciliary body to advance, and the zonules to relax. “Presbyopia affects 100% of the population aged over 45 and cataracts 70% of the over 65s”This causes the elastic capsule containing the crystallin of the lens to mould it into a spherical shape, increasing its optical power so the eye can focus on objects nearer to it. With ageing, the radius of curvature of the crystalline lens decreases and the distribution of the index gradient changes This produces a shift in the spherical aberration towards higher positive values, such that the compensation of the positive spherical aberration that takes place in the young eye is lost. Also, as the eye ages, although the ciliary muscle and the capsule retain most of their function, the lens loses elasticity, such that the capsule is not able to change the shape of the lens to respond to a near stimulus, therefore losing accommodation capacity.

Moreover, at more advanced ages the denaturing of the proteins of the lens gradually turn it more opaque (cataracts), leading to progressive loss of vision.


Cornea y cristalino

Of over-65s cross-sectional image of the cornea and lens in a young eye, captured using the Scheimpflug imaging system. PI: reflection from the anterior of the cornea; PIII: reflection from the anterior of the lens; PIV: reflection from the posterior of the lens.



Statistics
Presbyopia affects 100% of the population aged over 45 and cataracts affect 70% of people over 65 (and eventually 100% of the population if they live long enough). It is estimated that there are over 209 million presbyopia sufferers in Europe (44% of the total population and 22% of the workforce) and it is forecast that by 2030 half of Europe’s population will have presbyopia.

Moreover, each year around 14.2 million cataract operations are carried out around the world. With the progressive ageing of the population and increased life expectancy in industrialised countries, these figures are set to rise sharply in the years ahead.


Replacement of the lens with an intraoccular implant
The only treatment available for cataracts is to surgically remove the lens and replace it with an intraocular lens implant (IOL).

The procedure has undergone spectacular improvements in recent years, to the point where it is a highly effective outpatient operation. The most commonly used technique is phacoemulsification, a technique whereby the lens is ruptured by ultrasound and aspirated out of the eye via a tiny incision through the cornea and capsule. The latest generation of implants are injected into the eye folded, through an incision of no more than 3.2 mm. The replacement lens is inserted into the capsule through the incision made earlier and held in place with haptics which lodge in the lens equator. A variety of intraocular lenses are available on the market, using hydrophilic or hydrophobic materials, with different shaped surfaces, different lens edge profiles, various haptic designs, etc. Developments in lens design have focused on increasing biocompatibility, avoiding subsequent opacification of the capsule, improving the predictability of refraction, perfecting their mechanical stability, and optimising the optical quality of the eye. Revenues from the global market for intraocular lenses were 730 million euros in 2004 and are expected to rise to 1,825 million euros in 2010.

Although most implants use monofocal lenses (which aim to correct refraction at a single focal point, usually distant focus), increasingly often multifocal intraocular lenses are being implanted in order to give the eye a greater depth of focus so as to partly compensate for its inability to “The only treatment available for cataracts is to surgically remove the lens and replace it with an intraocular implant”accommodate. Indeed, even before cataract surgery, the options for correcting presbyopia have been extended beyond traditional reading glasses and progressive glasses (alternate vision), to other options that provide simultaneous near and distant focusing (simultaneous vision). These include multifocal contact lenses or even refractive corneal surgery for presbyopia. In these cases, multifocality is achieved by introducing several simultaneous foci (as in diffractive intraocular lenses or intraocular lenses or contact lenses with concentric zones of differing optical powers), or by introducing aberrations, nominally increasing depth of focus at the expense of a reduction in the optical quality achieved by the best focus.

The ideal treatment for presbyopia would be to restore accommodation by using intraocular lenses that are able to change refractive power in response to a stimulus triggering the accommodation response.



Maps of ocular aberrations (imperfections) in a cataract patient given a spherical-geometry intraoccular lens implant (left) and an asphericalgeometry intraoccular lens (right). A more uniform map is indicative of better optical quality. Aspherical intraoccular lenses improve optical quality by enabling better focusing than conventional spherical geometry lenses. The values in the image are phase shift measurements in microns.



Restoring the optical quality of the young eye
Conventional monofocal intraocular lenses have a spherical surface. This geometry enables the desired power to be achieved, but the spherical aberration of the young lens is negative, compensating, at least in part, for the spherical aberration of the cornea. In the last few years a new generation of lenses has been developed with an aspherical surface which aims to emulate this feature of the young eye. “The young eye is able to change its radius of curvature to focus on objects at varying distances”Lenses exist with an aspherical geometry on the front, back or on both, and depending on the model, they are designed with a negative spherical aberration so as to wholly or partially correct for the population’s average positive spherical aberration, or not induce spherical aberration.

This type of lens improves the optical quality of the eye by reducing its aberrations, and in general reducing its tolerance of being defocused. Given that these are monofocal lenses, the patient will only be corrected for distance vision, and will depend on glasses or other techniques to perform tasks which need close-up vision.


Imitating the accommodative capacity of the lens
The young eye is able to change its radius of curvature to focus on objects at different distances. The ideal intraocular lens to implant during cataract surgery (and in younger patients to replace a transparent lens in presbyopia), and function entirely satisfactorily, would be one that is able to change its power dynamically so as to focus on near and distant objects, thus restoring the “Although accommodative intraocular lenses are the solution of the future when it comes to correcting presbyopia, significant scientific and technical progress still needs to be made”eye’s accommodative capacity. Developing lenses able to do so would have a huge social and economic impact. Various types of accommodative lens have been put forward, and although some have reached the market, only one model has been approved by the US Food and Drug Administration (FDA). These lenses aim to utilise the action of the accommodative mechanism to change the power of the eye, either by displacing the intraocular lens axially, by modifying the distance (axial or lateral) between two lenses in a composite intraocular lens, or changing the radius of curvature of the surfaces of the intraocular lens. So far, despite significant technical progress, none of these lenses has proven itself able to provide a significant accommodative range or adjust the refraction correctly in the unaccommodated state. The possibility of filling the capsule with a polymer to replace the crystallin of the lens has also been explored, although this alternative has run into problems such as the later opacification of the capsule.

There is no doubt that while accommodative intraocular lenses are the solution of the future when it comes to correcting presbyopia, significant scientific and technical progress still needs to be made until they become a genuinely effective option.


The Visual Optics and Biophotonics Laboratory at the Instituto de Óptica (CSIC)
Research into the accommodation mechanism and the ageing of the crystalline lens is the key to progress towards new techniques to correct it. The Visual Optics and Biophotonics Laboratory is developing technology ranging from optical coherence tomography of the anterior segment of the eye to adaptive optics enabling the quantitative measurement of the optical and structural properties of the eye, and the lens in particular, relating the optical quality of the ocular components with visual quality. It has obtained pioneering results concerning the changes in optical imperfections (ocular aberrations) with ageing and accommodation, and in measuring the geometry and position of the crystalline lens with accommodation.

Our research group provided the first measurements of the map of ocular aberrations in vivo for intraocular lenses implanted in patients operated for cataracts, and comparisons of the optical quality of spherical and aspherical geometry lenses. It has also provided explanations on the effectiveness of multifocal patterns in contact lenses and intraocular lenses, methods to optimise refractive corneal surgery, and new optimised designs of monofocal intraocular lenses. Its research in this field is aimed at understanding the basic mechanisms of accommodation and ocular ageing, and adaptation of vision in order to conceive of new designs to compensate for presbyopia and restore accommodation.

Profile: Susana Marcos

(Salamanca, 1970) After obtaining her PhD in Physics from the University of Salamanca she earned a Fulbright Postdoctoral scholarship on Human Frontiers at the University of Harvard. She is currently a research professor at the CSIC’s Instituto de Óptica and director of the institute, where she also leads the Visual Optics and Biophotonics Group. She has represented the Vision Sciences area in various scientific societies (Optical Society of America, Sociedad Española de Óptica and the Association for Research in Vision and Ophthalmology). She has also edited the journals Vision Research and Biomedical Optics Express and has received various awards: Adolph Medal from the Optical Society of America, ICO Prize (Abbe Medal) from the International Commission for Optics and the European Young Investigator Award, among others. She is also a distinguished member of the Optical Society of America and the European Optical Society.

Published in No. 02


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