In vivo detection method and imaging device for fundus autofluorescence

Abstract

This allows early detection and precise localization of changes that precede drusen (BLamD and BLinD) in vivo. [Solution] A method for detecting autofluorescence in the fundus of an eye (2) in vivo includes the steps of: a) providing an optical signal (4) having a predetermined wavelength in the short wavelength range; b) detecting a first eye position and dividing the fundus into a grid consisting of a plurality of pixels according to the detected first eye position; c) determining an area of ​​the fundus to be examined by selecting a plurality of pixels; d1) exciting the fundus of the pixels in the area to be examined using the optical signal (4); d2) detecting a further fundus position different from the first fundus position and tracking the grid according to the detected further fundus position; e) detecting at least one luminescence signal (8) emitted from the pixels of the fundus; f) providing the luminescence signal to an evaluation unit (9); and g) repeating steps d1) to f) for each pixel in the area to be examined.

Description

[Technical Field]

[0001] The present invention relates to a method for detecting autofluorescence of the fundus in vivo. [Background technology]

[0002] Age-related macular degeneration (AMD) is the most common cause of blindness in developed countries. In Germany alone, it affects more than 5 million people. Currently, only the advanced, late-stage form of AMD is treatable. There is no cure, especially for the early and intermediate forms. Early and intermediate forms of AMD are defined, among other things, by the development of drusen and changes in the retinal pigment epithelium. Precursor features include deposits in the region of the basal layer of the retinal pigment epithelium (RPE), known as basal layer deposits (BLamD), and deposits between the basal layer of the RPE and the inner collagen layer of Bruch's membrane, known as basal line deposits (BLinD), which are observed in normal aging and AMD. Summary of the Invention [Problem to be solved by the invention]

[0003] To improve diagnosis and treatment, early detection of drusen changes and deposits, even before they are clinically apparent, is essential, and no method for achieving this is known in the prior art.

[0004] In view of the above circumstances, an object of the present disclosure is to enable early detection and accurate localization of changes that precede drusen (BLamD and BLinD) in vivo. [Means for solving the problem]

[0005] This object is solved by the subject matter of claim 1. Preferred embodiments can be found in the subclaims.

[0006] According to one embodiment of the present invention, there is provided a method for detecting fundus autofluorescence in vivo, comprising: 1. A method for detecting autofluorescence in the fundus of an eye (2) in vivo, comprising: a) providing an optical signal (4) having a predetermined wavelength in the short wavelength range; b) detecting a first eyeball position and dividing the fundus into a grid of a plurality of pixels according to the detected first eyeball position; c) determining an area of ​​the fundus to be examined by selecting a plurality of pixels; d1) exciting the fundus of the pixels of the area to be examined with a light signal (4); d2) detecting a further fundus position different from the first fundus position and tracing a grid according to the detected further fundus position; e) detecting at least one luminescence signal (8) emitted from a pixel of the fundus; f) feeding the light emission signal to an evaluation unit (9), g) Steps d1) to f) are repeated for each pixel in the region to be inspected.

[0007] In this example, "fundus" refers to the area behind the transparent vitreous body in the inner wall of the eye, including, among other things, the retina, retinal pigment epithelium (RPE), basement membrane, Bruch's membrane, and villi.

[0008] "In vivo" refers to fundus examination in a living patient or organism.

[0009] "Tracking" refers to correcting the position of the eye during the examination. Eye movements are recorded and taken into account during the recording of the emission signal. In particular, tracking is performed using a tracking system that works in constant feedback with the scanning unit that records the emission signal.

[0010] It has been shown that after the fundus is stimulated with specific light, these deposits or precursors of drusen exhibit autofluorescent properties and can be visualized microscopically as flat sub-RPE deposits using a luminescent signal.

[0011] Therefore, the method not only detects tympanic membrane deposits or precursors, but also accurately locates them on the living eye, even when the eye's position is constantly changing, which is an important point of the present invention. The eye or fundus is subdivided by a grid. This grid is tracked even when the eye moves and the position of the eye changes, so that the fundus can be scanned along the same pixels even when the position of the eye changes.

[0012] Preferably, the excitation and measurement for each pixel is repeated multiple times to generate an overall averaged luminescence signal. By repeatedly exciting and scanning while constantly tracking the eye position, multiple luminescence signals can be recorded per pixel and combined into an average luminescence signal. This minimizes uncertainty and improves the overall quality of the measurement.

[0013] According to a preferred embodiment of the present invention, the method further comprises: h) determining whether deposits are present in the fundus based on the luminescence signal (8); i) Assigning deposits to pixels.

[0014] The deposits exhibit autofluorescence properties when excited with specific light. The luminescence signals can be examined using appropriate evaluation algorithms. The luminescence signals characteristic of drusen precursors can be detected and assigned to individual pixels. In this way, typical deposits of precursors in the fundus can be detected and localized based on their luminescence signals.

[0015] According to a preferred embodiment of the present invention, the predetermined wavelength can be selected from the range between 350 nm and 750 nm, preferably between 360 nm and 500 nm. In principle, this method can be used to detect drusen as well as pre-drusen. The occurrence of autofluorescence in drusen and pre-drusen requires different wavelengths. The characteristic luminescence signals for drusen and pre-drusen can be detected and assigned to individual pixels. For this purpose, a light signal with a corresponding broad electromagnetic spectrum, preferably in the blue or dark blue to violet wavelength range, is required. In this way, the luminescence signals can be used to detect and localize not only drusen but also typical pre-drusen deposits in the fundus.

[0016] According to a preferred embodiment of the invention, the predetermined wavelength can be continuously adjusted, which allows continuous excitation of the fundus. In this way, the excitation wavelength can be matched to the structure to be examined, so that autofluorescent structures can be excited particularly efficiently and simply with different excitation wavelengths.

[0017] According to one embodiment of the present invention, a spectral imaging apparatus for detecting autofluorescence of the fundus of an eye in vivo comprises: a light source that generates an optical signal having a predetermined wavelength in a short wavelength range for exciting at least one region of the fundus; a position correction unit having a tracking system for detecting and tracking the position of the eye; a scanning unit configured to scan at least one region of the fundus according to the position of the eye; a sensor that detects a light emission signal emitted from the fundus according to the position of the eyeball; It is equipped with:

[0018] The light source is preferably a laser light source, which generates laser light having a predetermined wavelength.

[0019] In this embodiment, a position correction unit is understood to be in particular a unit that is able to detect the position of the eye and correct it by means of a tracking system, in this way the eye movements can be tracked and taken into account when scanning the fundus. The position correction unit and the tracking system are in particular realized by software that synchronizes the image recording of the fundus according to the deviations caused by the eye movements.

[0020] The sensor for detecting the emission signal emitted by the fundus is particularly composed of a camera that scans the fundus pixel by pixel. Preferably, the sensor is composed of a sensor specifically designed for optical coherence tomography (OCT). This type of sensor allows for pixel by pixel scanning of the fundus. Alternatively, the camera is composed of a snapshot camera. A snapshot camera is a camera that can take multiple snapshots. In this way, existing OCT systems or low-cost snapshot cameras can also be used in the imaging device according to the invention.

[0021] According to a preferred embodiment of the present invention, the light source is configured to generate an optical signal having a predetermined wavelength in the range of 350 nm to 750 nm, preferably in the range of 360 nm to 500 nm, so that the light source can generate different wavelengths to excite different structures, allowing the spectroscopic imaging device to be used to detect multiple different changes in tissue.

[0022] According to a preferred embodiment of the invention, the scanning unit is made up of a plurality of deformable mirrors that can be controlled and changed for precise alignment, thus performing the function of a scanning laser unit, in which the fundus can be scanned pixel by pixel with an optical signal and the luminescence signal can be detected.

[0023] The spectroscopic imaging device further includes an evaluation unit for determining the presence or absence of deposits in the fundus based on the luminescence signals and for localizing the deposits based on the position of the eye. The evaluation unit analyzes the detected luminescence signals and filters out luminescence signals indicative of deposits or pre-stage drusen. These luminescence signals are then locally assigned. Preferably, the luminescence signals can be post-processed using the evaluation unit. The post-processing includes, in particular, decomposition of the luminescence signals and / or dimensionality reduction of the data using non-negative matrix factorization. For this purpose, matrices with non-negative real entries are linearly decomposed into rank-1 factors. Using special algorithms, it is possible to find a decomposition in which the individual factors are also non-negative. This requirement often leads to a decomposition that is easy to interpret and expresses the data as a sum of clearly separated components. Preferably, the post-processing of the data is optimized for detecting signals in the wavelength range below 450 nm. [Effects of the Invention]

[0024] According to a preferred embodiment of the invention, the light source comprises an excitation filter for filtering the optical signal. Even more preferably, the sensor comprises an emission filter for filtering the luminescence signal. In this way, the optical and / or luminescence signals can be limited to the wavelength range relevant for the examination, with unavoidable wavelengths outside the relevant spectrum being particularly easy to filter out. [Brief explanation of the drawings]

[0025] [Figure 1] 1 illustrates a schematic diagram of a method for in vivo detection of fundus autofluorescence according to a preferred embodiment of the present invention; [Figure 2a] 1 illustrates schematically a spectroscopic imaging device according to a preferred embodiment of the present invention; [Figure 2b] The histological representation of the deposits in the fundus is shown schematically in vertical section. DETAILED DESCRIPTION OF THE INVENTION

[0026] Preferred embodiments of the present invention will now be described in more detail with reference to the drawings.

[0027] FIG. 1 shows a schematic diagram of a method for detecting fundus autofluorescence in vivo. In the first step (a), an optical signal 4 is provided to excite the fundus. The optical signal 4 covers a wavelength range of 350 nm to 750 nm, preferably 360 nm to 500 nm, and can be continuously adjusted within this range. In the second step (b), the subject's eye is measured. That is, the initial eye position is determined. The fundus at this eye position is divided into a grid and subdivided into multiple pixels. The area to be examined is then determined by selecting multiple pixels that form this area.

[0028] Next, in steps d1) and d2), for each pixel in the area to be examined, the fundus of this pixel is targeted and stimulated with a light signal 4. At the same time, the position of the eye is constantly monitored and the virtual grid is adjusted according to the current position of the eye. In this way, each pixel is specifically targeted without being displaced by eye movements. In the following step e), a light signal 8 emitted from the fundus is detected and made available to an evaluation unit 9 in f).

[0029] The scanning, i.e. the targeting of individual pixels with simultaneous tracking of the eye position, is repeated for each pixel of the area under examination g). All luminescence signals 8 are then analyzed and evaluated. In a first step h), it is determined whether the luminescence signal 8 is characteristic of a deposit and thus indicates a precursor to a deposit or drusen in the fundus. If this is the case, in a second step i), this characteristic luminescence signal 8 can be traced back to the luminescent pixel and the location of the deposit can be identified.

[0030] FIG. 2a shows a schematic diagram of a spectroscopic imaging device 1 for detecting in vivo autofluorescence of the fundus of an eye 2 according to a preferred embodiment of the present invention. The spectroscopic imaging device 1 includes a light source 3 designed to generate an optical signal 4 in the form of a laser beam having a wavelength in the blue or dark blue range. The optical signal 4 for stimulating the fundus is filtered by a stimulation filter 11 before being passed to a scanning unit 6. The scanning unit is provided with multiple deformable mirrors 10 that can be selectively controlled and moved to deflect the optical signal 4 both vertically and horizontally. The scanning unit 6 is coupled to a position correction unit 5, which constantly monitors the position of the eye and adjusts the mirrors accordingly, thereby controlling the individual virtual background pixels that move with eye movement. The luminescence signal 8 emitted from the fundus is first filtered by an emission filter 12 and then detected by a sensor 7. The evaluation unit 9 is coupled to the sensor 7 so that the luminescence signal 8 is directly transferred to the evaluation unit 9. The evaluation unit 9 then detects deposits or precursors of drusen in the fundus and localizes them according to the tracked pixels.

[0031] Figure 2b shows a schematic histological representation of deposits in the fundus in a vertical cross section. Small deposits, in particular, can be visualized using the imaging device described above. The imaging device generates an en face image. Four structural layers are shown: retinal pigment epithelium I, Bruch's membrane II, choroid III, and choroid IV. Sub-RPE deposits can be detected in the area between Bruch's membrane II and RPE I. Not only small deposits, such as low-risk drusen A, are visualized. Rather, the method and spectroscopic imaging device 1 according to the present invention also allow for the detection of microdrusen B, as well as basal linear deposits and their precursors (pre-BLinD, BLinD) C, which can be easily distinguished from surrounding structures upon general microscopic examination. [Explanation of symbols]

[0032] 1. Spectroscopic imaging device 2 eyes 3 light source 4 Optical Signals 5 Position correction unit 6 Scan Unit 7 Sensors 8 Light Emitting Signal 9 Evaluation Unit 10 mirror 11 Excitation Filter 12 Emission Filter 13 images I Retinal pigment epithelium (RPE) II Bruch's membrane III Villi IV choroid A. Hard, low-risk drusen B. Microdrusen C BLinD

Claims

1. A method for detecting autofluorescence in the fundus of an eye (2) in vivo, comprising: a) providing an optical signal (4) having a predetermined wavelength in the short wavelength range; b) detecting a first eye position and dividing the fundus into a grid of pixels corresponding to the detected first eye position; c) determining an area of ​​the fundus to be examined by selecting a plurality of pixels; d1) exciting the fundus of the pixels of the area to be examined with a light signal (4); d2) detecting a further fundus position different from the first fundus position and tracing a grid according to the detected further fundus position; e) detecting at least one luminescence signal (8) emitted from a pixel of the fundus; f) feeding the luminescence signal to an evaluation unit (9), g) Repeat steps d1) through f) for each pixel in the region under test. method.

2. 10. The method of claim 1 further comprising: h) determining whether deposits are present in the fundus based on the luminescence signal (8); i) Assigning deposits to pixels method.

3. 3. The method of claim 1 or 2, The predetermined wavelength can be selected from the range between 350 nm and 750 nm, preferably between 360 nm and 500 nm. method.

4. 3. The method of claim 1 or 2, A predetermined wavelength can be continuously tuned method.

5. A spectral imaging device (1) for detecting autofluorescence of the fundus of an eye (2) in vivo, comprising: a light source (3) for generating an optical signal (4) having a predetermined wavelength in the short wavelength range for exciting at least one region of the fundus; a position correction unit (5) comprising a tracking system for detecting and tracking the position of the eyeball; a scanning unit (6) for scanning at least one area of ​​the fundus according to the position of the eyeball; a sensor (7) for detecting a light emission signal (8) emitted from the fundus according to the position of the eyeball; A spectroscopic imaging device (1) comprising:

6. 6. A spectroscopic imaging device (1) according to claim 5, The light source (3) is configured to generate an optical signal (4) having a predetermined wavelength in the range of 350 nm to 750 nm, preferably in the range of 360 nm to 500 nm. Spectroscopic imaging device (1).

7. A spectral imaging device (1) according to claim 5 or 6, The scanning unit (6) is composed of a plurality of deformable mirrors (10). Spectroscopic imaging device (1).

8. A spectral imaging device (1) according to claim 5 or 6, an evaluation unit (9) for determining whether deposits are present in the fundus based on the luminescence signal (8) and for localizing the deposits based on the position of the eyeball; The spectroscopic imaging device (1) further comprises:

9. A spectral imaging device (1) according to claim 5 or 6, The light source (3) has an excitation filter (11) for filtering the optical signal (4). Spectroscopic imaging device (1).

10. A spectral imaging device (1) according to claim 5 or 6, The sensor (7) has an emission filter (12) for filtering the emission signal (8). Spectroscopic imaging device (1).

Images