Patent Description:
The macular pigment is found in the macula of the human eye, the part of the retina associated with vision's highest resolution (see, e.g., <NPL>). The Macular Pigment is of dietary origin, and hence, the amount of pigment is related to the individual's diet. It is believed that higher optical density is related to better retinal health. It is proposed that higher density of the pigment may have a protective role against retinal diseases such as macular degeneration. Studies have shown that the macular pigmentation can play an important role in preventing eye diseases and improvement of visual function (see, for example, <NPL>; and <NPL>).

Age-related macular degeneration (AMD) is one of the leading causes of blindness in Western countries. Due to the lack of a fully effective treatment, prevention is of great importance. There is growing evidence that nutritional intervention may reduce the incidence of macular degeneration, or at least reduce its progression.

In particular, modification of dietary intake or food supplements may lead to an increase of specific carotenoids in the retina (lutein (L) and zeaxanthin Z) that comprise the macular pigment (MP). When such supplements are administered, monitoring the optical density of the macular pigment density (MPD or MPOD) are of great importance.

To date, the instruments capable of measuring the density of the macular pigment are either subjective based on psychophysical methods, such as heterochromatic flicker photometry (HPF), or high-end devices which capture images of the retina at two wavelengths. In these instruments, the macular pigment density is calculated from the relative absorption of the blue spectrum which is characteristic of the absorption spectrum of the macular pigment.

The area of a human eye where the macular pigment is located has a characteristic absorption spectrum, which can be seen in <FIG> (see, for example, <NPL>).

Psychophysical devices have been used for over three decades in the measurement of macular pigment density (see, for example, <NPL>; <NPL>; and <NPL>). There are several commercial devices based on heterochromatic flicker photometry (HFP), such as the MPSII (Elektron Technology, Cambridge, UK), which are well established in the clinical assessment of MPOD. However, they have a serious limitation due to the very nature of the subjective method that is not always comprehensible by the patient and can provide inconsistent results.

Optical methods are based on comparative analysis of two images of the fundus of the eye at blue and green. The intensity images is proportional to the reflectance of the fundus of the eye at those wavelengths. Given that most of the light is reflected from layers located posterior to the macular pigment is, changes in reflectance are attributed to the absorption of the macular pigment.

The procedure for determining the density of the macular pigment from the relative intensities can be found in the literature (see, for example, <NPL>). This document shows the application of the Fundus Reflectometry an imaging system. Two recorded at different wavelengths (blue and green) images examined by comparison to derive the difference in reflectance of the fundus of the eye. The macular pigment density can be calculated from reflectance data using an appropriate formula.

The document of <NPL>, discloses an instrument based on the principle of double-pass optical integration adapted for fast measurements of straylight in the human eye. The instrument utilizes a light source formed by an array of green LEDs that is projected onto the ocular fundus. The source has two concentric parts, a disk (field angle <NUM>-<NUM> degrees) and an annulus (<NUM>-<NUM> degrees) that are modulated at different frequencies. A silicon photomultiplier receives the light reflected from the central part of the fundus and the Fourier transform of the signal reveals the contribution of each part of the source. Their relative amplitude is used to quantify light scattering by means of the straylight parameter. The measurement method, utilizing rotational symmetry and coding filed angles with different frequencies eliminates the need for a high-performance camera and allows fast measurements. This approach can be further advanced with multiple wavelengths and field angles to perform other measurements such as that of the macular pigment density.

The document of <NPL>, discloses an optical instrument to perform in-vivo measurements of macular pigment density (MPD). It uses a simplified methodology over conventional multispectral imaging techniques. The instrument is easy to use and comfortable for patients, so it can be used in clinical environments to control the MPD in patients. The method for the measurement of MPD consists in projecting temporally modulated light of different wavelengths (blue: <NUM> and green: <NUM>) at two different areas of the fundus. Each source is divided in one disk and one concentric annulus that can be modulated independently. Both sources are projected simultaneously. The light returning from tha fundus is detected with a photomultiplier. The Fourier transform of the signal reveals the relative reflectance of the macula and the surrounding area in each of the used wavelengths. The illumination and light-sensing arms are spatially separated at the pupil plane to eliminate unwanted effects of backscatter light and Purkinje reflections. The required pupil diameter for measurement is <NUM> and the total duration of the measurement was 270msec. In this way the signal can be acquired within the latency interval of the pupillary response to the flash. An analysis of the signals provides with a direct estimate of MPD.

<CIT> discloses methods and systems for imaging the fundus of the eye, in which the fundus is illuminated through a mask which blocks light from reaching one or more masked regions within a peripheral area surrounding a target area of interest, such as the macular region. An image is obtained of both the target area and the peripheral area. A scattered light value is derived from the image intensity within the masked regions, and this is used to compensate and adjust the measured intensity of light within the target area. When employed in the measurement of macular pigment optical degeneration (MPOD), an improved measurement is obtained in which the specific image(s) used for measurement have a specifically calculated correction factor applied to compensate for light scatter, rather than relying on population-based average scattering values.

Optical methods are objective, unlike psychophysical method which are subjective; however they require more expensive components (such as highly sensitive cameras) and / or electro-optical elements such scanning systems and require non-trivial image processing. Moreover, measurements with these systems may have errors associated with ambient light.

Based on the above, there is a need for a new optical technique for measuring the density of the macular pigment which is more practical, compact, and robust repetitive.

The object of the present invention is to provide an optical instrument and a corresponding method for measuring the density of the macular pigment in the eye that deals with the aforementioned drawbacks.

The present invention provides an optical instrument for measuring the density of the macular pigment in the eye which comprises the features defined in claim <NUM>.

The invention also provides a method for measuring the density of the macular pigment in the eye employing an instrument of the invention and comprising the following steps defined in claim <NUM>.

The present invention therefore provides an optical instrument for measuring the density of the macular pigment that is objective, fast, compact and robust, and an associated method. The instrument does not depend on subjective responses of each subject, since it directly measures the optical density of the macular pigment (objectively) and not through its visual effects on the subject of measurement (subjectively).

Below is illustrated in a non-limiting manner the object of the present invention with reference to the accompanying drawings in which:.

<FIG> shows a graph of the characteristic absorption spectrum of the macular pigment of the macular area of a human eye.

<FIG> shows schematically a section of a human eye, where the light reflected from the macula M is attenuated due to the presence of macular pigment. In this figure (from prior art) blue light is depicted in continuous lines and green light in dotted lines. The relative reduction in blue reflectance (between the periphery <NUM> and the macula <NUM>), using green light as reference (macular pigment affects insignificantly green light; periphery <NUM> and macula <NUM>), can be used to calculate the macular pigment density.

<FIG> shows the principle of fundus reflectometry applied in the Fourier domain. A light source <NUM> comprising of a central part <NUM> and peripheral part <NUM> is projected onto the fundus of the human eye so that the central part <NUM> is projected onto the macular area M. The light source <NUM> consists of two sources <NUM>, a green one and a blue one, both distributed in the central part <NUM> and peripheral part <NUM> of source <NUM>.

The light sources are modulated at four different frequencies f1, f2, f3 and f4, corresponding to the green center, green periphery, blue center and blue periphery respectively. The response signal from the fundus is collected by the photodetector <NUM>. The Fourier analysis reveals the amplitude for each frequency. Knowing which frequency corresponds to each wavelength and location (center or periphery) the macular pigment density can be calculated as described above.

Modulation frequencies are in a range between <NUM> and <NUM>.

<FIG> shows the optical arrangement of the invention, for the projection of the source on the fundus and the capture of the reflected signal. A light source <NUM> has a central part <NUM> and peripheral part <NUM>. A combination of lenses <NUM> and diaphragms <NUM> are used to project the light source on the fundus such that the central part <NUM> is projected onto the macula. The light source <NUM> is modulated into four different frequencies corresponding to the green center, green periphery, blue center and blue periphery. The response signal from the fundus is received by the detector <NUM>. The Fourier analysis reveals the amplitude of each frequency. Knowing which frequency corresponds to which wavelength and retinal location (center or periphery) one can calculate the macular pigment density. One or more cameras <NUM> are used for the alignment of the eye under investigation.

<FIG> shows a construction of a light source comprising of two separate light sources (each characterized by a central and a peripheral part) according to the invention, where the two sources have the desired wavelengths (blue and green) and the two sources are combined with a suitable dichroic mirror that allows the transmission of the green wavelength while reflecting the blue wavelength. Blue light is depicted with continuous lines and green light with dotted lines.

According to one embodiment, the light source consists of a central part and a peripheral part, distributed in a ring arrangement. The light source is modulated in four different frequencies corresponding to the center (green), periphery (green), center (blue) and periphery (blue). In one preferred embodiment, the wavelength of blue light is between <NUM> and <NUM> and is produced by Light Emitting Diodes (LED); also, the wavelength of the green light is between <NUM> and <NUM> and is emitted by different LEDs. The central and peripheral parts of the light source have concentric opaque walls separating the green light and blue light LEDs that they are projected in both the central part and the peripheral part of the source. The appropriate electronics allow the control of each LED group separately to the desired modulation frequency. An appropriate combination of lenses and diaphragms form images of the light source of LEDs on the retina. The light source is projected onto the fundus such that the central part is projected on the macula (central fovea). This is accomplished by asking the subject to look at the center of the source using a fixation stimulus.

A telescopic system conjugates optically a diaphragm D1 to the desired area of the pupil of the eye. In addition, a second diaphragm D2 is placed in front of detector <NUM> conjugated to a different part of the pupil. Thus, the light reaching the detector <NUM> is light originated solely from the fundus, eliminating reflected light in other ocular media, particularly the cornea.

Light reflected from the fundus is recorded by photodetector <NUM>. A Fourier analysis performed on a computer provides the light intensity for each frequency. Knowing which frequency corresponds to which wavelength and retinal location (center or periphery), the macular pigment density is calculated. One or more additional cameras <NUM> may be used for alignment of the eye during the measurement.

Claim 1:
- An optical instrument for measuring the density of the macular pigment in the eye, comprising:
- a light source (<NUM>),
- several lenses (L1, L2, L3) located between the light source and the eye to study,
- a first diaphragm (D1) conjugate to the eye pupil plane to allow control of the entrance position of the light in the eye,
- a photodetector (<NUM>),
- a mirror (M) that directs the light exiting the eye to the photodetector (<NUM>),
- a second diaphragm (D2) conjugated to the pupil plane of the eye, which determines the output path of the light from the fundus of the eye,
- at least one lens (L4) between the second diaphragm (D2) and the photodetector (<NUM>), characterized in that the light source (<NUM>) comprises two separate light sources, a green light source and a blue light source, each with a central part (<NUM>) and a peripheral part (<NUM>), with a dichroic mirror placed in front of both light sources so that the lights emitted hit the dichroic mirror, which is configured to transmit the green light and to reflect the blue light, the two separate light sources of the light source (<NUM>) being modulated at four different frequencies corresponding to green light in the central part, green light in the peripheral part, blue light in the central part and blue light in the peripheral part, each of the two separate light sources of the light source (<NUM>) adapted to be projected on the fundus of the eye, so that the central part (<NUM>) of each of the two separate light sources of the light source (<NUM>) is projected onto the macula of the eye, and the peripheral part (<NUM>) of each of the two separate light sources of the light source (<NUM>) is projected onto the peripheral portion of the fundus, and in that the photodetector (<NUM>) is arranged to receive the response signal from the fundus of the eye, and in that the optical instrument comprises means for recording the received response signal.