Explanation of the lens paradox.

Abstract

The lens paradox is the phenomenon in which the curvature of the human eye lens increases (steepens) with age, yet most human eyes do not become more powerful as they get older. One explanation of this phenomenon resides in changes in the refractive index distribution of the lens of the eye. This study provides the first noninvasive measurements of refractive index distribution that support this explanation of the lens paradox. The lens of the human eye is a mass of densely packed cellular tissue filled with protein and contained within an elastic capsule. Unlike most man-made lenses, it has a nonuniform refractive index, such that the refractive index increases from the surface inwards to the center. This “gradient index” is an important contributor to the power of the lens. In fact, because of the gradient, the power of the lens is greater than it would be if the refractive index were constant and equal to the highest value inside the lens. The lens grows throughout life. New cells, shaped as long fibers, continually form and wrap around older cells without any of the cells being discarded. As part of this growth, the lens becomes thicker and its surfaces become more curved. It would therefore be expected that the lens, and hence the eye itself, should become more powerful and that there would be a trend towards eyes becoming myopic with age (Figs. 1a and b). However, the opposite occurs, with the majority of eyes changing in the opposite direction (hypermetropia) by an average of approximately 2 D between the ages of 30 and 60 years 8 (Fig. 1c). Brown coined the term “lens paradox” for this apparent contradiction. Because the power of the cornea at the front of the eye does not become weaker with age, 10 the most likely explanation for the lens paradox is an age-dependent change in the refractive index of the human lens. Confirmation of this has been limited by a paucity of experimental results for the refractive index distribution, particularly in a plane containing the optical axis of the lens. Attempts by a number of authors to explain the lens paradox have therefore relied on theoretical modeling of the refractive index distribution and of possible changes to the distribution with age. Suggested changes due to age include a reduced amplitude of refractive index variation through the lens, or a change in refractive index profile across the lens. In the former case, either the refractive index of the outer cortex could increase or the refractive index of the inner nucleus could decrease, while for the latter the gradient index profile could become flatter in the middle of the lens and then increase in steepness towards the edges. Theoretically, all of these are possible. It should be mentioned that another hypothesis that has been put forward to explain the lens paradox is that there is a decrease in eye length with age. This was based on analysis of biometric data from the late 1950s. However some more recent measurements do not support this theory, 13 although it is still considered to be a possibility. We have investigated the change in gradient index with age and its effect on lens power using magnetic resonance micro-imaging. A preliminary description of the method has been given previously and a similar technique has been applied to measure the refractive index gradient in fish eye lenses. The technique relies on the nuclear magnetic resonance transverse relaxation rate R2 1/T2 for water protons being linearly dependent on protein concentration. Human lenses were obtained from the Queensland and New South Wales Eye banks and stored at 34.5°C in artificial aqueous humor. The artificial aqueous humour (AAH) was made under sterile conditions using Auto-Pow minimum essential medium with Earl’s salts (MEME: ICN Biochemicals, Costa Mesa, CA), with the addition of HEPES (10 mm), glutamine (2 mm), penicillin (1000 g l ), streptomycin (1 mg l ) amphotericin (10 mg l ) and adjusted to a pH of 7.4. Some lenses were stripped of their capsule and homogenized by hand mixing with a stainless steel spatula. Homogenates of various concentrations were made and refractive index measured using an Abbe refractometer. Measurements of transverse relaxation rate R2 were made on a Bruker MSL200 NMR spectroscopy/micro-imaging system, using a standard Carr-Purcell/Meiboom-Gill pulse sequence 19 with a 180° pulse spacing of 4.2 ms. A plot of refractive index n as a function of R2 showed a strong linear correlation: