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Restoring accommodation: a dream or an approaching reality?

2005; Wiley; Volume: 25; Issue: 1 Linguagem: Inglês

10.1111/j.1475-1313.2004.00264.x

1475-1313

W. N. Charman,

Ophthalmology and Visual Impairment Studies

Over much of the world, modern times have seen a steady extension in life expectancy. In the UK, for example, life expectancy at birth almost doubled between 1841 and 1998, from approximately 40 to 80 years for women and 75 years for men. As well as enhancing the typical lifespan, better nutrition, sanitation and medical care have preserved bodily vigour for much longer, so that, for example, marathon-running pensioners are no longer a curiosity. Yet, with all these changes, the inexorable fall in our amplitude of accommodation with age continues in essentially the same way as that recorded by Donders (1864) more than a century ago, with an almost linear decline in objective amplitude from a peak around the age of 10 to 0 at around 50 (e.g. Charman, 1989). Those who favour more natural methods may well ask whether there are genetic, dietary or environmental factors which influence the age at which presbyopia occurs. Can presbyopia be delayed by manipulating any of these? Although in the earlier literature 'poor' diet is often mentioned as a factor leading to early presbyopia (e.g. Duke-Elder and Abrams, 1970) the nature of the optimal diet has not apparently been identified, although an adequate intake of antioxidants may perhaps be beneficial in slowing ageing processes in the lens and elsewhere in the eye (e.g. Brown et al., 1998; Jacques et al., 2001; Chylack et al., 2002). Similarly, clear ethnic or other genetic influences have yet to be found. There is, however, some evidence that higher ambient temperatures may accelerate the decline in accommodation (Miranda, 1979, 1985; Weale, 1981), although the reality of even this effect has been challenged (Kragha and Hofstetter, 1986). At present, then, there appears to be little that any individual can do to delay the onset of presbyopia. This sobering loss of an adequate amplitude of accommodation to carry out normal, everyday tasks, at an age when many like to feel that they are still in their prime, has, of course, led to the development since the 18th century of an increasingly sophisticated range of bifocal, trifocal and varifocal spectacle lenses (e.g. Levene, 1977). More recently similar, though optically less satisfactory, ranges of presbyopic contact lenses (Charman and Saunders, 1990) and intra-ocular lenses (IOLs) have also become available and attempts have been made to produce similar bifocal or multifocal effects at the cornea by excimer laser ablation (Vinciguerra et al., 1998). Monovision, in which one eye is corrected for near and the other for distance, has also become popular as a mode of contact lens, and to a lesser extent IOL, excimer laser and conductive keratoplasty (Allamby and Heavens, 2003) correction for presbyopia. The presbyopic patient is, of course, the mainstay of many optometric practices. Yet few would deny that, however sophisticated the design of current corrective modalities might be, they do not match the flexibility and performance of natural accommodation. All wearers of presbyopic spectacle lens corrections will have encountered the problem of wanting to view near or distant objects in directions other than those for which their lenses provide appropriate correction, while contact lens or IOL designs which provide satisfactory vision over a range of distances all involve losses of image contrast or other compromises. Monovision involves the penalty of impaired stereopsis and suppression unless the difference in corrections is modest. All these current approaches are, of course, 'static' corrections in the sense that the correcting lenses and eye do not change power when objects at different distances are viewed. Instead, either an effective power change is achieved by relative movement between the lens and eye, as in spectacle bifocals when the visual axes are depressed to look through the near correction, or the depth-of-focus is extended to embrace both far and near distances, as in multifocal contact lenses and IOLs: in monovision visual tasks at near and far are effectively switched between the two eyes. This contrasts with the true dynamic power change of the crystalline lens occurring during natural accommodation. Given this situation, it is not surprising that the search continues for ways in which a single-vision correction can be made to actively change power over its full aperture, so that clear vision over a wide range of distances is obtainable in any desired viewing direction. Further, given the widespread public demand for preservation of youthful appearance and device-free vision, it is recognised that an even better solution would be a method by which at least a limited dynamic change in true ocular power could be preserved or restored. The quest for a satisfactory design of 'accommodating' corrective spectacle lens has already been a long one and has yet to find true success. Suggested designs have largely centred upon liquid-filled lenses bounded by flexible membranes which can change shape to vary the power, and liquid crystal designs in which the power change is achieved by a change in refractive index produced by an appropriate electric field (e.g. Bennett, 1973; Fowler and Pateras, 1990; Charman, 1993; Pateras et al., 1993). With the liquid-filled lenses, which rely on pumping additional liquid into the lens to change the curvature of the flexible surface and increase power for near vision, the problem has usually been one of robustness against both liquid leakage and damage to the flexible membrane. The liquid crystal devices have so far been too cumbersome to be practical. A new, untried, possibility is the 'fluid lens' in which two immiscible liquids of differing refractive index (e.g. conducting saline and an insulating silicone oil) are confined in a shallow cylindrical container, whose inner walls and one face are given a water-repellent coating. The boundary between the liquids is curved and can be made to change its radius by applying a DC field across the coating to change its water-repellent properties. Small prototype lenses (diameters up to 6 mm) show remarkable ability to change power, from 0 to +20D in 10 ms (Technology applications, 2004). However, even if their technical problems can be overcome, power changes in all these devices have to be actuated by hand or some automatic sensing device when viewing distance is changed, adding a further element of complexity and expense. In addition, most of the designs have other disadvantages, such as thickness, the need for a power source or limitations on lens shape. This makes the alternative idea of preserving or revitalising the natural accommodative system correspondingly more attractive, with the goal of amplitude of at least 3D to cover the range between normal reading distances and infinity. An obvious first step to preserving and/or restoring accommodation is to fully understand the nature of presbyopic change. Surprisingly, even today there is by no means unanimity on this issue (e.g. Glasser and Kaufman, 1999; Weale, 2000; McLeod, 2002). Undoubtedly lenticular change plays a major role, with the lens becoming thicker and less elastic while retaining the same equatorial diameter, but loss of capsular elasticity, reductions in the circumlental space, decreased mobility (as distinct from decreased contractility) of the ciliary muscle, geometrical and other factors may also be implicated. Different workers give different degrees of importance to these various factors (e.g. Weale, 1989; Atchison, 1995; Gilmartin, 1995; Glasser and Campbell, 1998, 1999). Some have even challenged the conventional Helmholtz-based understanding of accommodation itself (Schachar, 1992; Schachar et al., 1995). However, all agree that the ciliary body retains its strength for many years beyond the onset of presbyopia (Swegmark, 1969; Fisher, 1977, 1986; Strenk et al., 1999), although it does show changes in both geometry and structure (Pardue and Sivak, 2000). As many authors have found that, as it ages, the natural lens becomes harder to deform (Fisher, 1971; Glasser and Campbell, 1998, 1999), while the capsule retains some elasticity (Fisher, 1969a), it is natural to consider the possibility that the natural lens might be replaced by some man-made, bio-compatible material which mimics that of the youthful crystalline lens in terms of its optical and mechanical properties (Kessler, 1964; Parel et al., 1986). Some at least temporary success has been achieved in this direction in in vivo animal studies involving the injection of silicone gel (Haefliger et al., 1987; Nishi and Nishi, 1998) or inflatable endocapsular balloons (Nishi et al., 1993) into the intact lens capsule: claims have been made from the Vision Cooperative Research Centre of the University of New South Wales that a method applicable to humans and yielding 6–8D of accommodation is on the verge of successful development (Young, 2003). Very recently, studies using young porcine lenses have explored the effects of refilling the capsule with different volumes of silicone oil, while keeping the ciliary body and zonule intact, and have shown that the refilled volume has an important effect on the lens power and accommodation achieved (Koopmans et al., 2004). However, with this approach serious questions remain concerning the possibility of long-term changes in both the material of the implant and the lens capsule. The work of Koopmans et al. (2004) suggests that it may be difficult to control the final refractive power of the lens with sufficient accuracy (although this may be easier if the refractive index of the gel can be selected, Ho et al., 2001), while a homogeneous filling of the capsule cannot mimic the optical advantages conferred by the gradients of refractive index of the natural lens. A related approach in which, rather than replacing the older, more rigid lens, lens rigidity is reduced by YAG laser photodisruption of the nucleus and cortex has been tried with some claimed success on cadaver lenses (Krueger et al., 2001) but does not appear to have been pursued further, possibly because of the high subsequent risk of cataract development in the living as opposed to the cadaver eye. A second surgical method was originally inspired by somewhat unconventional ideas on the accommodation process (Schachar, 1992; Schachar and Anderson, 1995; Schachar et al., 1995; Schachar, 2001). Unlike the usually accepted theory originating with Helmholtz in which ciliary contraction reduces zonular tension and lens diameter, while increasing lens power (see, for example Ciuffreda, 1991), these ideas hold that the arrangement of zonular fibres is such that when the ciliary muscle contracts, tension in the key fibres attached to the lens equator increases, increasing the equatorial diameter of the lens. The inhomogeneous nature of the lens is such, however, that the central region of the lens increases in curvature in spite of the increase in lens diameter, while the lens periphery flattens. On the basis of these ideas, Schachar and his colleagues suggested that the development of presbyopia chiefly depends on the fact that the gap between the equator of the lens and the inside of the ciliary ring reduces with age, as is indeed observed (e.g. Strenk et al., 1999). This reduction is thought to impair the ability of the zonular fibres to change their tension over the range required to produce the changes in lens shape that underlie accommodation. If this is true, it follows that if the width of the circumlental gap could be increased, accommodative amplitude would be enhanced. This has led to techniques such as scleral expansion banding (Schachar, 1992; Schachar et al., 1995; Yang et al., 1997, 1998; Roy, 2001; Schachar, 2001; Qazi et al., 2002), in which short PMMA bands are inserted into the superficial sclera, and anterior ciliary sclerotomy (Thornton, 1996), in which radial incisions are made over the ciliary body, in attempts to expand the ciliary ring and hence restore accommodation. These approaches assume, of course, that once potential zonular tension is increased, the older, less elastic, natural crystalline lens is capable of making the larger shape changes required to increase the amplitude of accommodation. Although on the basis of subjective measurements the protagonists of these ideas have claimed that their methods are successful, the few independent objective studies of the patients have found little evidence for a true increase in accommodation rather than an increase in depth-of-focus (Elander, 1999; Mathews, 1999; Kaufman, 2001; Malecaze et al., 2001; Ostrin et al., 2004) and the efficacy of the basic concept remains questionable at the present time. Moreover, there may be a significant risk of a variety of post-operative complications (e.g. Singh and Chalfin, 2000; Vetrugno and Cardia, 2001). The third approach, which is now being vigorously explored by many surgeons, involves the use of novel designs of 'accommodating' intraocular lens (IOL). Although design details vary, most of these are equipped with haptics which, when compressed, move the IOL's optic forward towards the cornea to increase the overall power of the eye for near vision, the compression either being applied directly by the ciliary body or via the lens capsule (e.g. Cumming et al., 2001; Küchle et al., 2002). Although, as pointed out by Thomas Young some two centuries ago (Young, 1801), the movement of a single lens over the few millimetres available in the eye cannot produce the large amplitude of accommodation observed in young people, even a change as low as 1D would be of great value in pseudophakia, In practice, several factors would be expected to influence the effective amplitude of accommodation achieved, including the IOL design and power and the eye's corneal radius and axial length (Nawa et al., 2003). Dual-optic IOL designs incorporating two longitudinally separated elements may in theory give a greater degree of power change for the same degree of linear movement (Hara et al., 1990; McLeod et al., 2003), and one single-optic design claims that it permits flexure of the optic as well as longitudinal movement, so that both these effects can contribute to an 'accommodation' of 3D at the spectacle plane (Guttman, 2003). A further promising new design (Ben-Nun and Alió, 2004) relies on shape changes in the surface of a transparent flexible material which is compressed between a plate fixed in the sulcus and a piston which is actuated by pressure from the intact lens capsule induced by the action of the ciliary body: the flexible material bulges through a hole in the fixed plate, the changing curvature of the free surface producing the required power change. Although much development work remains to be done, the principle has been demonstrated in an animal model. In clinical studies of currently available accommodating IOLs, there is still a certain amount of controversy over whether true changes in ocular power always occur with lenses of this type or whether the observed ability to achieve good vision at both distance and near is at least partly a depth-of-focus effect due perhaps to small pupils, some residual myopic astigmatism or high levels of corneal spherical aberration or multifocality (Tucker and Rabie, 1980; Nakazawa and Ohtsuki, 1984; Datiles and Gancayco, 1990; Lea et al., 1990; Sawusch and Guyton, 1991; Werblin, 2001). Nevertheless, in 12 patients (aged 45–87 years, mean age 71 years) with an implanted accommodating IOL, Küchle et al. (2002) found a median objective change in accommodation of 1.2D by streak retinoscopy and a median anterior chamber depth change of 0.63 mm. These results are compatible with the theoretical expectations (Leyland and Bloom, 1999; Nawa et al., 2003). Moreover during the 3-month follow-up period of their study, Küchle et al. (2002) found no evidence of any marked fibrosis of the lens capsule. Although Mastropasqua et al. (2003) found significant capsular fibrosis in 30% of their accommodating IOL patients (aged 54–75 years) after 6 months, the subjective amplitude with the accommodating lens was approximately 2D higher than that of a control group with conventional single-vision IOLs, somewhat higher than the value of approximately 1D found by Langenbucher et al. (2003) who used a commendable variety of techniques to assess the accommodation achieved in their group of patients aged 41–87 years. Thus, at least in the short term, it does appear that these early accommodating IOL designs are capable of restoring a useful amount of accommodation, with good distance and reading acuities. It is interesting that the approximately 5 mm diameter anterior capsulorhexis required to remove the material of the natural crystalline lens and insert the accommodating IOL does not apparently affect the ability of the capsule to transmit the changing ciliary and zonular forces to the IOL. The question of whether long-term changes in the lens capsule or in the IOL itself may limit the usefulness of this type of IOL remains to be answered. Fisher (1969a,b), e.g. found that the capsule continued to lose elasticity throughout life, with Young's modulus decreasing by a factor of approximately four between the ages of 50 and 80. Clearly, apart from the possibilities of capsular opacification or loss of elasticity, there is also a risk that one or more of the haptics of the IOL might fail to flex, leaving it tilted or fixed in an inappropriate position and introducing some unwanted ametropia and aberration. In general, then, many questions remain to be answered regarding suggested surgical methods of restoring accommodation. All invasive surgery carries a risk and it may be legitimately argued that this risk is only justified in the presence of disabling cataract. The degree of potential success in all the methods depends upon the importance of particular components of the accommodative system in the development of presbyopia. If lens rigidity is the primary problem, then scleral expansion surgery and its variants cannot work: if presbyopia is multifactorial, with capsular change making a strong contribution, then accommodating IOLs may not function. At present there is disagreement as to the relative importance of these components, so that it is difficult to predict the potential of particular techniques. Undoubtedly, then, the results of today's clinical trials, even if unsuccessful in restoring accommodation, will throw valuable light on the fundamentals of accommodation. It is, perhaps, unfortunate that none of the published papers to date have related patient outcome to the age and other characteristics of the individual patient, as these would be expected to strongly influence outcome. The methods used to assess post-operative accommodation are also often inadequate. Objective methods must be applied to avoid depth-of-focus ambiguities and here it may be that the new generation of wavefront aberrometers with internal accommodation targets will prove useful in not only measuring the true dioptric power changes but also in assessing the contribution of such factors as corneal multifocality to the subjective amplitude. What does this mean for the optometrist in practice? Clearly, presbyopes are going to continue to increase both in absolute numbers and as a fraction of the total population. Providing them with effective spectacle or contact lens corrections will therefore be a priority for many years. However, if the views of their protagonists are correct, it may well be that accommodating IOLs are implanted not only in an increasing fraction of cataract patients but also in presbyopes whose lenses are still clear. This would undoubtedly demand significant changes in traditional patterns of prescribing for the older age group, as the number of pseudophakics in the UK already runs into seven figures.