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Are there advantages in implanting a yellow IOL to reduce the risk of AMD?

2004; Wiley; Volume: 82; Issue: 2 Linguagem: Inglês

10.1111/j.1600-0420.2004.00248.x

1600-0420

Sven Nilsson,

Ophthalmology and Visual Impairment Studies

Both cataract surgery, including the use of different types of intraocular lenses (IOLs), and age-related macular degeneration (AMD) are subjects of frequent articles in Acta Ophthalmologica (Algvere & Seregard 2002; Lundström et al. 2002; Frennesson 2003; Stordahl & Drolsum 2003; Gustavsson & Agardh 2004) and in other ophthalmological journals. In relation to such articles, it may be of interest to discuss the light-absorbing properties of an IOL with regard to the possible risk of longterm retinal damage. In cataract surgery, a more-or-less yellow lens is removed and replaced by a clear IOL. If the increasing shift in the colour of the lens represents nature's way of protecting the ageing retina and retinal pigment epithelium against short-wavelength light, it would be natural to replace the lens with a yellow IOL. It is worthwhile studying the published evidence supporting such a notion. It has been known for a long time that exposure to short-wavelength light may cause photochemical damage to the retinal photoreceptors –‘the blue light hazard’– with a maximum damage at approximately 440 nm. Whereas higher levels of irradiation cause thermal damage, lower levels cause photochemical damage (Sliney & Wolbarsht 1985). On this basis, it would appear to be more important to protect the eye from blue light than from yellow and red light. As an example, one should make certain that sunglasses absorb sufficient blue light. Is there any evidence in clinical studies to suggest that blue light may contribute to age-related maculopathy (ARM) and AMD? The answer seems to be ‘Yes’, both from short-term experimental studies and longterm population studies. Firstly, the terminology should be made clear. Age-related macular degeneration is divided into two main subgroups. The first is early AMD, more correctly termed age-related maculopathy, in which soft drusen and pigment clumping represent the most important signs. The second is late or severe AMD, which includes wet AMD (i.e. pigment epithelial detachment and choroidal neovascularization) and severe dry AMD. Of the population studies that have presented evidence pertinent to the question of whether broad-spectrum light may contribute to AMD, one of the most important is the large and longterm Beaver Dam Eye Study, carried out in the USA. This involved about 5000 individuals, aged 43–84 years. The amount of time spent outdoors between the ages of 13 and 19 years and between 30 and 39 years was significantly associated with development of both early and late AMD (Cruickshanks et al. 1993, 2001). Furthermore, it was found that the use of a hat and sunglasses provided significant protection against soft drusen maculopathy. As regards blue light, a significant association (p = 0.05) between blue light exposure during the previous 20 years and severe AMD was found in watermen working at Chesapeake Bay, USA (Taylor et al. 1992). Because cataract surgery entails removing a yellow lens and replacing it with a clear lens, the retinal exposure to blue light will increase after surgery. Does this lead to an increased risk of AMD? There are conflicting reports in the literature regarding this issue. While some studies of smaller groups of patients do not report such an increase in risk, the large Beaver Dam Eye Study shows an association between previous cataract surgery and late ARM. In this part of the study, 3700 patients (aged 43–86 years) were followed for 5 years and 2800 were followed for 10 years. Cataract surgery before baseline was significantly associated with the incidence of late AMD (relative risk (RR) 3.81), exudative macular degeneration (RR 4.31), progression of ARM (RR 1.97) and pure geographic atrophy (RR 3.18) at follow-up (Klein et al. 2002). This is further supported by the recently published, pooled findings from the Beaver Dam and Blue Mountain Eye Studies, where a total of 6000 patients were followed for 5 years. The risk of late AMD, particularly neovascular AMD, was 5.7 times higher for non-phakic than for phakic eyes (Wang et al. 2003). In all cases, the confidence intervals were convincing. Even if inflammatory reactions are believed to be involved in macular changes after cataract surgery, this extensive, longterm study seems to indicate that the blocking of blue light by a yellow IOL may be a favourable measure for reducing the risk of later severe AMD, at least in younger members of the population subjected to cataract surgery. Experimental results may explain why the blue part of the spectrum is more dangerous than the other parts. Regarding the retina, it has been unequivocally shown in recent animal experiments that ‘the blue light hazard’ is mediated through absorption of blue light by rhodopsin, the rod photopigment (Grimm et al. 2001). Normal animals with rhodopsin and knock-out animals without rhodopsin but with an otherwise normal retina were exposed to blue or green light. Thermal effects were prevented by the use of suitable filters. The green light did not damage any of the animals, whereas the blue light caused severe retinal damage in the animals with rhodopsin but not in the knock-out mice. Thus, it is very important to observe this difference between blue and green light. Yellow and red light would have involved an even smaller risk of damage. As a consequence, a blue light-absorbing yellow IOL may be of longterm value. Damage to the retinal pigment epithelium (RPE) by blue light is also evident from experimental work. This is important, as the earliest signs of AMD are considered to arise in the RPE. It is well known that the photoreceptor outer segments are unstable and have to be renewed continuously through the formation of new membrane discs at the base (Nilsson 1964; Young 1967) and through phagocytosis of the outer segment tips by the RPE (Young 1967). Up to the age of about 30 years, the phagosomes are fully degraded in the RPE, but thereafter residual bodies (lipofuscin) of non-degradable products are accumulated. It has been shown that lipofuscin is very sensitive to blue light, which creates reactive oxygen species in the lipofuscin bodies. There is a great risk that these reactive species will damage the membrane surrounding the lipofuscin bodies, releasing reactive oxygen species and lytic enzymes to the cytoplasm, in turn damaging or killing the RPE cell. In our own experiments on cultured RPE cells, 20 min of exposure to blue light killed approximately 50% of cells containing large amounts of lipofuscin, whereas only about 10% of cells with very few lipofuscin granules were killed (Wihlmark et al. 1997). The ultraviolet part of the spectrum does not reach the retina, at least not in amounts sufficient to cause any damage. Debris resulting from this ageing process of the RPE cells seems to be extruded extracellularly, first as basal laminar deposits and then as drusen into Bruch's membrane (Feeney-Burns & Ellersieck 1985; Hageman et al. 2001). Soft, confluent drusen involve a large risk of development of CNV (i.e. exudative AMD) (Pauleikhoff et al. 1990; Sarks et al. 1994). Activated macrophages, releasing vascular endothelial growth factor, act as an intermediate step (Polverini et al. 1977; Killingsworth et al. 1990). Thus, accumulation of lipofuscin in the RPE and subsequent RPE damage after blue light exposure of the lipofuscin seem to be important initial steps in the chain of events leading to exudative AMD. As a consequence, it would appear logical to protect the ageing RPE from longterm, daily exposure to blue light, by, for example, implanting a blue light-absorbing yellow IOL in cataract surgery, especially in the younger part of this patient group. Finally, we performed experiments on eyes in pigmented rabbits, which were exposed to broad-spectrum xenon light. The irradiance was clearly below that causing thermal damage. A clear polymethylmethacrylate (PMMA) material used for IOL production was placed in front of one eye and a yellow filter in front of the other eye. The yellow filter attenuated the light from about 400 nm to about 500 nm, with a maximal attenuation at 430 nm (65%) to 440 nm (55%). Electrophysiological recordings showed significantly more damage to both retinal and RPE function for eyes behind the PMMA material than for eyes behind the yellow filter (Nilsson et al. 1990). In order to investigate whether a neutral density filter would protect the retina and the RPE to the same extent as a blue light-absorbing yellow filter, the clear PMMA material was combined with a neutral density filter, making the total irradiance on the eye behind the PMMA material equal to that behind the yellow filter. The neutral density filter did not protect retinal and RPE function better than the PMMA material alone. In addition to the above, it is well known that a yellow filter enhances contrast sensitivity, which is of particular interest in low contrast environments. In conclusion, there is evidence from experimental work on animals and on cultured cells, as well as from large and longterm population studies, that exposure to light contributes to the development of AMR and AMD and that it is the blue part of the spectrum that is dangerous. On this basis, it seems advisable to replace the ageing, yellowing lens with a blue light-absorbing yellow IOL in cataract surgery, especially in younger patients. Naturally, it is very important to check that a yellow IOL actually absorbs in the relevant region of the spectrum.