Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008
.pdf3 Aging Effects on the Optics of the Eye |
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cornea in microns for a 4-mm diameter pupil, again as a function of the age of the subjects. Although there is an increase in the aberrations of the cornea, it is small and cannot completely explain the decrease observed in the optical performance of the complete eye with age. This fact leads us to another very important issue. How does the relationship between the aberrations of the cornea and the internal surfaces of the eye—and, in particular, the lens—change with age? In other words, are the increases in the aberrations of the whole eye with age due to an increase of the aberrations of each ocular component, or rather to progressive decoupling of the aberrations? We have extensively addressed this question in several studies by comparing both corneal and ocular aberrations as a function of age.
Coupling of Corneal and Internal Aberrations as a Function of Age
The amount of aberrations for both the cornea and internal optics was found to be larger than for the complete eye in young subjects, indicating a significant role of the internal ocular optics to compensate for the corneal aberrations producing an improved retinal image. During normal aging, the relatively small corneal changes can not account for the degradation in retinal image. The lens changes both its shape and the effective refractive index dramatically with age, however, and its aberrations as a consequence. In this context, it seems possible that, at least in part, the increase in aberrations of the eye with age could be due to the loss of the aberration balance between cornea and lens that seems to be present in the younger eye.
Figure 3.8 shows both the RMS of the wave-aberration for the complete eye and for the anterior surface of the cornea. Corneal aberrations in the younger subjects are larger than the total ocular aberrations, indicating that the internal optics compensates for the corneal aberrations. The opposite occurs in older subjects, however, where the cornea has lower aberrations than the complete eye. This indicates that the lenses in the older eyes do not compensate, but in fact add aberrations to those of the cornea.
As an example, Fig. 3.9 shows examples of wave-aberrations for the cornea, internal surfaces and the eye—for a typical young eye (upper plots) and for a typical old eye (bottom). In the young eye, the cornea and the internal optics aberrations have a similar magnitude and shape, but are opposite in sign, producing an eye with overall lower aberrations. However, in the older eye, this finely tuned compensation is not present.
Optics of the Aging Eye and Intraocular Lenses
This better understanding of the ocular optics in the aging eye was used for designing new and more effective ophthalmic optics. For instance, the ideal substitute for the natural lens in a cataract eye is not an intraocular lens with the best isolated
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Fig. 3.8 RMS of the aberrations of the eye (squares) and the cornea (circles) as a function of age
Fig. 3.9 Examples of wave aberrations for the anterior corneal surface, the internal surface, and the complete eye in a young and older eye, respectively
optical performance, but rather one designed to compensate for the aberrations of the cornea (see schematic example in Fig. 3.10).
An improved design for an intra-ocular lens would have an aberration profile that compensates (at least partially) for the corneal aberrations in the older eye, to maximize the quality of the retinal image. A first approximation is the use of aspheric intraocular lenses to correct for the corneal spherical aberration. Other type of lenses—for instance, correcting corneal coma—have also been proposed.25
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Fig. 3.10 Schematic representation of the coupling of the cornea and an intraocular lens. A lens without aberrations will produce an eye with the aberrations of the cornea and relatively poor retinal images. However, a lens with aberrations approximately contrary to those of the cornea will produce an eye nearly free of aberrations
In the future, it may also be possible to have customized lenses correcting most corneal aberrations in situ and maximizing retinal image quality.
In addition to aberrations, other optical (mainly intraocular scatter) and post-optical (neural) factors further influence visual performance of older subjects. All those factors have to be considered together when predicting or analyzing visual performance.
Acknowledgments Part of the research described in this chapter has been supported by the Ministerio de Educación y Ciencia (MEC) in Spain, and by AMO_Groningen (The Netherlands). The author also wishes to thank all his collaborators in his laboratory at Murcia University and elsewhere who greatly contributed in many of the aspects of the research briefly described here.
References
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2.Owsley C, Sloane ME (1990) Vision and aging. In: Boller F, Grafman J (eds). Handbook of Neuropsychology, vol 4. Elsevier Science Publishers B.V. (Biomedical Division), pp 229-249
3.Owsley C, Sekuler R, and Siemsen D (1983) Contrast sensitivity throughout adulthood. Vision Res 23:689-699
4.Artal P, Ferro M, Miranda I, and Navarro R (1993) Effects of aging in retinal image quality. J. Opt. Soc. Am. A 10:1656-1662
5.Burton KB, Owsley C, Sloane ME (1993) Aging and neural spatial contrast sensitivity: photopic vision. Vision Res. 33:939-946
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6.Guirao A, González C, Redondo M, Geraghty E, Norrby S, and Artal P (1999) Average optical performance of the human eye as a function of age in a normal population. Invest. Ophthalmol. Vis. Sci. 40:197-202
7.Jenkins TCA (1963) Aberrations of the eye and their effects on vision: part 1.Brit. J. Physiol. Opt. 20:59-91
8.Calver R, Cox MJ, and Elliot DB (1999) Effect of aging on the monochromatic aberrations of the human eye. J. Opt. Soc. Am. A, 16(9):2069-2078
9.McLellan JS, Marcos S, and Burns SA (2001) Age-related changed in monochromatic wave aberrations of the human eye. Invest. Ophthalmol. Vis. Sci. 42:1390-1395
10.Ijspeert JK, de Waard PWT, van den Berg TJTP, and de Jong PTVM (1990) The intraocular straylight function in 129 healthy volunteers; dependence on angle, age and pigmentation. Vision Res. 36:699-707
11.Guirao A, Redondo M, and Artal P (2000) Optical aberrations of the human cornea as a function of age. J. Opt. Soc. Am. A. 17(10):1697-1702
12.Glasser A, and Campbell MCW (1998) Presbyopia and the optical changes in the human crystalline lens with age. Vision Res. 38:209-229
13.Artal P and Guirao A (1998) Contribution of the cornea and the lens to the aberrations of the human eye. Optics Letters 23:1713-1715
14.Artal P, Guirao A, Berrio E, and Williams, DR (2001) Compensation of corneal aberrations by the internal optics in the human eye. Journal of Vision, 1(1):1-8
15.Artal P, Berrio E, Guirao A, Piers P (2002) Contribution of the cornea and internal surfaces to the change of ocular aberrations with age. J. Opt. Soc. Am. A. 19:137-143
16.Santamaría J, Artal P, Bescós J (1987) Determination of the point-spread function of the human eye using a hybrid optical-digital method. J Opt Soc Am A. 4:1109-1114
17.Artal P, Marcos S, Navarro R, Williams DR (1995) Odd aberrations and double-pass measurements of retinal image quality. J Opt Soc Am A. 12:195-201
18.Díaz-Doutón F, Benito A, Pujol J, Arjona M, Güell JL, Artal P (2006) Comparison of the Retinal Image Quality with a Hartmann-Shack Wavefront Sensor and a Double-Pass Instrument. Invest. Ophthalmol. Vis. Sci. 47:1710-1716
19.Liang J, Grimm B, Goelz S, and Bille JF (1994) Objective measurement of the WA’s aberration of the human eye with the use of a Hartmann-Shack sensor. J. Opt. Soc. Am. A. 11:1949-1957
20.Liang J and Williams DR (1997) Aberrations and retinal image quality of the normal human eye. J. Opt. Soc. Am. A 14:2873-2883
21.Prieto PM, Vargas-Martín F, Goelz S, and Artal P (2000) Analysis of the performance of the Hartmann-Shack sensor in the human eye. J. Opt. Soc. Am. A. 17:1388-1398
22.Iglesias I, Berrio E and Artal P (1998) Estimates of the ocular wave aberration from pairs of double-pass retinal images. J. Opt. Soc. Am. A. 15:2466-2476
23.Guirao A and Artal P (2000) Corneal wave-aberration from videokeratography: accuracy and limitations of the procedure. J. Opt. Soc. Am. A. 17:955-965
24.Tabernero J, Piers P, Benito A, Redondo M and Artal P (2006) Predicting the optical performance of eyes implanted with IOLs to correct spherical aberration. Invest. Ophthalmol. Vis. Sci. 47:4651-4658
25.Tabernero J, Piers P and Artal P (2007) Intraocular lens to correct corneal coma. Opt. Lett. 32 (4):406-408
Chapter 4
Aging of the Cornea
Luciano Cerulli, MD, PhD and Filippo Missiroli, MD
Abstract Unlike other ocular structures, as well as most tissues in the body, the cornea does not show important changes with normal aging. A variety of corneal aging changes have, however, been reported. Few of them are clinically evident, while others are demonstrated by chemical, biological, and structural studies. Distinction has to be made between conditions considered within the normal limits of aging and those of true disease processes that commonly affect the cornea in the elderly. The difference with other ocular structures is that changes of cornea due to aging are mostly asymptomatic and do not usually affect vision, hence they do not require treatment. However, some changes occur and, for example, the aged cornea becomes more susceptible to infection because of a decreased ability to resist a variety of physiological stresses. Furthermore, it is sometimes difficult to distinguish age specific deterioration from degenerations modified by environmental and genetic factors. The well-known clinical conditions that occur with age in the cornea will be described first. Then, a review of the effect of age on shape and different aspects of the cornea and its structural (anatomical) changes will be reported.
Keywords Aging, cornea, corneal arcus, deep crocodile shagreen, astigmatism, corneal thickness, stroma, keratocyte, endothelium
Clinical Conditions
Corneal Arcus
Also known as gerontoxon is the most common bilateral manifestation of the aged cornea. It is characterized by a white ring around the peripheral cornea that is separated from the limbus by a clear zone 0.3 to 1 mm in width. It consists of deposits of cholesterol, cholesterol esters, phospholipids, and triglycerides. When it is seen in younger people, it is not an age-related condition (arcus senilis) but is in association with hyperlipoproteinemia types 2 and 3. Initially the superior and inferior peripheral
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Edited by C. A. P. Cavallotti and L. Cerulli © Humana Press, Totowa, NJ |
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Fig. 4.1 Peripheral ring of corneal arcus as seen at slit lamp
cornea is affected and, with time, a complete annulus forms. Slit lamp biomicroscopy reveals the extensive involvement of the subepithelial zone, the corneal stroma, and Descemet’s membrane, as well as fine opacities in the so-called lucid interval of Vogt which is optically clear on naked eye examination (see Fig. 4.1).1
Prevalence
In one study, the estimated prevalence was measured at 8 percent for those 40 to 49 years of age, 45 percent for those 50 to 59 years of age, and 75 percent for those 70 to 79 years of age. In another study, the prevalence was measured at 6 to 12 percent in a cohort of insulin-dependent patients with diabetes who were less than 30 years of age, and was measured at 49 to 54 percent for patients with diabetes who were more than 30 years of age. The tendency toward increasing prevalence with age explains the usage of the popular nomenclature arcus senilis, instead of the more technically correct term corneal arcus. In general, ar cus senilis is more common in men than it is in women. It is also more common among patients of African descent, and when it occurs in these patients, it tends to occur earlier in life. Arcus senilis may also be more common in patients who regularly consume alcoholic beverages, with the prevalence in one study increasing as the amount of alcohol consumption increased.3,4,5
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Biochemical Aspects
Palmitic, stearic, oleic, and linoleic acids are among the fatty acids that make up many of the deposited lipid molecules. Lipids are normally deposited in the cornea, but with aging, the amount of deposited lipids increases—in some cases it will result in arcus senilis. This supports the assumption that arcus senilis may represent an extension or exaggeration of the natural process of lipid deposition in the cornea.
A structural study showed extracellular solid spherical lipid particles (< 200 nm in diameter) enmeshed between collagen fibers. Immunostaining showed significant apoE and apoA-I, but very little apoB in the peripheral cornea. Cholesteryl ester-rich spherical particles accumulate in the extracellular spaces of the peripheral cornea. Most of these lipid particles are 40-200 nm in diameter, and are therefore similar in size to one type of cholesteryl ester-rich lipid particle that accumulates in the extracellular spaces of human atherosclerotic lesions. These extracellular lipid droplets seem to derive from direct deposition of plasma lipoproteins.2
Deep Crocodile Shagreen
Also known as mosaic degeneration, deep crocodile shagreen consists ofn bilateral, polygonal, grayish-white opacities that are interrupted by clear spaces that are usually asymptomatic (see Fig. 4.2). Two types of this condition exist:
Fig. 4.2 Both crocodile shagreen (white arrow) and limbal gridle of Vogt (black arrow)
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●Anterior shagreen (Vogt’s anterior mosaic crocodile shagreen) are seen in the deep layers of the epithelium or in Bowman’s layer, and become more apparent after instillation of fluorescein stain
●Posterior shagreen are generally seen in the central deep cornea, which makes it difficult to differentiate with a central cloudy dystrophy of the cornea
Both anterior and posterior forms do not require treatment. Deep crocodile shagreen is sometimes seen in association with peripheral band keratopathy or following trauma.6 Familial type may occur with x-linked megalocornea or in a juvenile form of anterior mosaic crocodile shagreen.
White Limbal Gridle of Vogt
Limbal gridle of Vogt is a very common, bilateral, age-related corneal degeneration. It is always asymptomatic and requires no therapy. It affects more than 50 percent of the population over age 40 and is characterized by a subepithelial degeneration and may include calcium deposits. The lesions look like white opacities of the peripheral cornea, forming a half moon-like arc running concentrically with the limbus—usually in the interpalpebral zone along the nasal and temporal limbus (only the horizontal meridian is affected). The opacities may be separated from the limbus by a clear zone of about 1 mm, or without a clear zone in between, and lie at the level of Bowman’s membrane and the immediately subjacent stroma.
Histopathology of the lesions show a destruction of Bowman’s membrane and superficial lamellae of the stroma in association with deposition of calcium and areas of hyaline and elastotic degeneration with hypertrophy of the overlying epithelium.6
Hassall-Henle Bodies
Also known as Hassall-Henle warts or Henle’s warts, these bodies are small hyaline excrescences on the posterior surface of Descemet’s membrane at the periphery of the cornea. Averaging 0.07 to 0.08 mm in diameter, they are constantly present in adults—occasionally they become confluent and macroscopically visible. They contain bounded material that is believed to be collagen, in which numerous cracks and fissures are filled with extrusions of the corneal epithelium. They represent an over activity of the formation of hyalin by the endothelial cells. They are found in large quantities in degenerations and chronic inflammations. When they become larger and more numerous, they invade the central area (cornea guttata). The condition is probably associated with the aging process.6,7
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Cornea Shape
Astigmatism
One of the most common ocular changes in the elderly is the variation of manifest refraction. Often this happens because a change in corneal curvature causes alteration in refraction—usually a change from the with-the-rule astigmatism to against- the-rule astigmatism.
The vertical meridian of the cornea is steeper than the horizontal meridian in with-the-rule astigmatism, so the eye has more refractive power (plus cylinder) along the vertical axis. In against-the-rule astigmatism, the horizontal meridian is steeper than the vertical and the eye has more refractive power (plus cylinder) along the horizontal axis.
Several studies confirmed that a decrease in the vertex radius occurs with aging, thus demonstrating a steepening of the cornea. A Japanese study of 2,161 subjects found that the prevalence of astigmatism increases and the axis turns to against- the-rule with age. The result of the linear regression analysis indicates that the age-related change in astigmatism is mainly associated with changes in the cornea.8
The corneal astigmatism was found to change in Hong Kong’s Chinese population, where both the corneal and spectacle astigmatism demonstrated a shift from with-the-rule to against-the-rule with age (keratometer and a computer-assisted videokeratoscope were used).9 Another Japanese study that used a autokeratometer revealed that the cylindrical diopter of with-the-rule astigmatism decreased, and against-the-rule astigmatism increased with aging.10 A study from Turkey suggested that the normal cornea becomes steeper in the horizontal line and superior vertical quadrant, and shifts from with-the-rule to against-the-rule astigmatism. The amount of physiological corneal astigmatism, however, does not change with age.11
A topographic analysis of the changes in corneal shape due to aging was carried out in 734 volunteers in Japan. The maps of subjects in their 70s and > 80 revealed a horizontal, oval-shaped steep area, suggesting against-the-rule astigmatism. The average-of-difference map demonstrated a marked corneal steepening at the horizontal meridians. In the data analysis of the averaged map, the mean refractive powers of the cornea increased with age.12
While corneal topography gives data of the anterior surface of the cornea, Scheimpflug photography is a useful tool with a non-contact technique that allows researchers to determine the shape and astigmatism of the posterior corneal surface. A study where Scheimpflug camera was used to measure the cornea of the right eye in six meridians of 114 subjects ranging in age from 18 to 65 years showed that, with aging, the asphericity of both the anterior and the posterior corneal surface changes significantly—a significant average change in the k value was found for the posterior surface, which indicates a shift to a more aspherical surface. The same study revealed that peripheral thickness along the perpendicular line at 3.75 mm from the apex showed an average difference of 19 micron between the young and the old subjects, while no difference in central corneal thickness was noted.13
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Corneal Thickness
The thickness of corneal tissue is an important parameter in refractive surgery, and its measurement is essential in the assessment and management of corneal diseases. In the last few years, it became an important clinical parameter for correct interpretation of Goldmann applanation tonometry results.
There are different instruments for determining corneal thickness, but the most widespread method currently in use is still ultrasonic pachymetry, even though it can be measured with other modalities—scanning-slit topography/pachymetry, specular and confocal microscopy, optical low-coherence reflectometry and rotating Scheimpflug camera. So far, ultrasonic pachymetry, scanning-slit topography/ pachymetry and rotating Scheimpflug cameras are considered more reliable tools for determining corneal thickness. In a recent study, Amano and others found that corneal thicknesses were comparable for the rotating Scheimpflug camera (Pentacam), ultrasonic pachymetry, and scanning-slit topography (Orbscan), with the acoustic equivalent correction factor. The measurements taken with the three instruments had significant linear correlations with one another, and all methods had highly satisfactory measurement repeatability.14 Several studies analyzed corneal thickness and its variation with aging, but the age-dependent difference in corneal thickness values remains unclear.
Age-related changes in central and peripheral corneal thickness were analyzed by the mean of the Orbscan II topography system. A thinning of the peripheral cornea was noted with increasing age. It was found that the mean corneal thickness was reduced with age (0.38mm/year), whereas the central corneal thickness was unaltered. These data concord with results of the previously mentioned study of Dubbelman obtained from the Scheimpflug camera.15
Rufer and others found slight variations in the mean central corneal thickness measured by the mean of Orbscan II system. In their work, no significant constant age-related trend was identified. However, there were raised values in the 50to 59-year olds and 70to 79-year olds when compared with all the other decades.16 In a Mongolian population where the central corneal thickness was measured using an optical pachymeter, there was a highly significant decrease in central corneal thickness with age—5 microns/decade in men, and 6 microns/decade in women.17 In a large series of eyes undergoing myopic refractive surgery, central corneal pachymetric measurements did not correlate with age.18 A large study where 1,699 Latino participants aged 40 or more years were included, central corneal thickness was measured by ultrasonic pachymeter. The most clinically significant finding was that when compared with normal Latinos aged 40 to 49 years, Latinos aged 70 or more years had substantially thinner corneas on average.19 Among participants of the European Glaucoma Prevention Study (EGPS), the central corneal thickness was higher in younger patients, male patients, and
diabetic patients.20
In a study population of different races, where central corneal thickness was measured by ultrasound pachymetry, an inverse relationship between age and CCT