US20040002694A1

US20040002694A1 - System and method for accurate optical treatment of an eye's fundus

Info

Publication number: US20040002694A1
Application number: US10/305,453
Authority: US
Inventors: Dirk Pawlowski; Wolfgang Neuberger
Original assignee: Ceramoptec Industries Inc
Current assignee: Ceramoptec Industries Inc
Priority date: 2000-05-12
Filing date: 2002-11-26
Publication date: 2004-01-01
Also published as: US20030009155A1; WO2001087181A2; WO2001087181A3; US6942656B2; EP1309283A2; EP1309283A4; US6494878B1

Abstract

A system and method is provided to accurately treat sites on an eye's retina employing computer based image generation, processing and central control means in conjunction with diode laser sources and optical fibers. The system is designed such that different photocoagulation and photochemical treatment methods alone or in combination can be performed and controlled to for simultaneous or consecutive treatment. The system and method accurately determines geometry of a treatment zone of a specific eye's fundus and adjust a treatment beam to irradiate the treatment zone with minimal coverage of adjacent tissue. Accordingly, also “forbidden zones” which would be severely damaged by the treatment beam are determined and their irradiation is prevented. The treatment zone is accurately determined with digital processing of angiographic data and slit lamp image data. Such image processing includes matching or alignment of two distinct images. This information is integrated with information on the treatment beam characteristics to better match treatment beam coverage with minimal overlap with healthy areas of the fundus. Additionally preferred embodiments also have the ability to automatically track eye movement and switch the beam source depending on eye movement, adjusting the beam spot area in real time.

Description

REFERENCE TO RELATED CASE

This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 09/569,438 filed on May 12, 2000 by Dirk Pawlowski and Wolfgang Neuberger, inventors, entitled “SYSTEM AND METHOD FOR ACCURATE OPTICAL TREATMENT OF AN EYE'S FUNDUS” and Ser. No. 10/208,218 filed on Jul. 30, 2002 by Dirk Pawlowski and Wolfgang Neuberger, inventors, entitled “METHOD FOR ACCURATE OPTICAL TREATMENT OF AN EYE'S FUNDUS”, and incorporated by reference herein[0001]

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the field of ophthalmology, in particular to the field of optical treatment of an eye's fundus using lasers. More specifically it deals with the application of computer based image generation, processing and central control means to accurately treat sites on an eye's retina, particularly its macula in connection with diode laser sources and optical fibers. Moreover, the present invention relates to a method and apparatus for application of different laser based treatment methods alone or in combination.

2. Information Disclosure Statement

Laser methods are widely accepted in modern ophthalmology for both treatment and diagnosis such as with laser scanning ophthalmoscopes. Treatment methods include laser reshaping of the cornea to correct strong myopic or presbyopic effects, laser surgery in the eye itself and a variety of retinal treatments. Retina related methods include conventional short-pulse and long-pulse photocoagulation laser systems, and more recently, Photodynamic Therapy (PDT) treatments of the retina. Short-pulse photocoagulation methods use green, yellow, red and infrared lasers (wavelengths from 514-810 nm) with high energy doses. The low-irradiance, long-pulse photocoagulation procedure referred to as transpupillary thermotherapy, or TTT, was first described for the use as an adjunct to radiotherapy in the treatment of choroidal melanomas. Choroidal melanomas as well as retinoblastomas respond to transpupillary thermotherapy (TTT) as is seen in histologic studies of TTT-treated choroidal melanomas that show extensive thrombosis of tumor vessels following treatment. Coagulation laser treatment is used to re-weld a detached retina to the back inner surface of the eye. Such detachment could lead to complete blindness.

Coagulation methods are also used to treat age related macular degeneration (AMD). The progression of AMD cannot be reversed, but it can be stopped to prevent the complete loss of eyesight. The disease is characterized by a typical blood agglomeration in the macula, the area of highest vision sensitivity of the retina.

Photodynamic therapy (PDT) is a method recently used in ophthalmology. In this treatment, a PDT drug is introduced into a patient's bloodstream. The drug is originally harmless and usually has no therapeutic effects, but it is sensitive to illumination at a certain wavelength. Long-pulse, low energy radiation is used to activate such drugs. If light of a suitable wavelength is absorbed by the drug molecules, they undergo a chemical reaction to another product, which is responsible for the therapeutic effect. In a simple case, this effect is the excitation of the drug molecule to an excited state where it can react with oxygen to form singlet oxygen, a highly reactive species. The singlet oxygen quickly reacts with nearby tissue to oxydize it, i.e. cause necrosis. Alternatively, the splitting of one molecule can create two radicals, which are chemically very reactive and can destroy body cells. Because this method is very selective, it prevents negative side effects of the therapy by restricting necrosis to the infected area. Typical applications for PDT include tumor treatments, catheter disinfection and dermatological applications.

PDT has also recently been applied for the treatment of age-related macular degeneration. In this treatment, the drug is given to the patient and after a certain time the macula is illuminated with a beam spot of light at the critical wavelength, preferably provided by a laser or a fiber coupled diode laser. The generated therapeutic substance then destroys blood agglomeration vessels and the degeneration of the macula is stopped. However, several disadvantages are associated with the state of the art in today's PDT methods. First, in many cases the effects seem to be temporary, with a high rate of recurrence and a resultant high re-treatment rate. Thus, such treatments are inconvenient and potentially expensive to the patient. It would be desirable to improve the method that is addressed in this invention.

As noted above, laser based methods of fundus treatment are widely accepted in today's ophthalmology and applied in different forms. In many of the treatments, focused laser beams are used, and it is necessary to control the treatment beam precisely in relation to the treatment area for a more efficient treatment and also to lower the risk of damaging healthy tissue.

Means for diagnosis of conditions like AMD include the use of fundus camera-generated images and fluorescence angiography, among others. In the latter, a certain fluorescing drug is added to the patient's blood circuit and then an image of the retina is taken. The fluorescing drug allows the exact visualization of all blood vessels on the retina. In the case of AMD for example, the blood vessels containing the a typical blood agglomerations responsible for the diseased state can be (and has to be) visualized by this method because the blood agglomerations do still circulate. The exact visualization of the treatment sites by fluorescence angiography is an essential prerequisite for laser eye treatments such as PDT, TTT, and green laser.

In WO 01/26591 [E. Reichel et al.] a method and system is claimed for treating a retinal tissue site using thermal therapy in combination with PDT or another treatment modality, and additionally controlling the treatments in response to feedback received from the retinal tissue site. However, this disclosure suffers from the fact that it does not describe how to accurately determine the treatment site, which is especially important for the application of different treatment beams from different optical systems to effectively treat the diseased sites.

In U.S. Pat. No. 5,336,216 [D. A. Dewey] a method for generating a treatment beam spot on the retina is claimed, which in particular generates a spot on the retina which has a rectangular intensity profile, also known as a top-hat profile for all sizes. However, this method suffers from the fact that knowledge about the treatment zone is only rudimentary, in that the ability to specifically determine the size and location of the treatment zone is limited. Treatment could be significantly enhanced if the treatment zone is well known and can be specifically targeted so that side effects like damaging healthy or sensitive tissues (“forbidden areas”) can be reduced.

This striking drawback of state of the art devices and methods, namely the extreme inaccuracy of the process, can be attributed to the lack of means for an accurate determination of the treatment zone and therefore the lack of beam area generating devices providing the desired accuracy. Because state of the art calculation of the energy density requires that the value of the diameter of the treating area is squared, inaccurate determination of the treating area results that can bear significant risks of damaging tissue.

The state of the art illumination means are designed such that it is impossible to obtain an illumination of the treatment zone alone. The operator has to calculate from fluorescence angiographic diagnostics how large the treatment area is, and then manually adjust the laser beam spot size to be large enough to completely cover the treatment area. This method is extremely inaccurate since no information about the specific eye is provided therein. The spot size on the retina varies with different patients, but the justification is absolute. This problem is addressed by the present invention.

Since typically used slit-lamp generated pictures are only of medium quality, the treatment zone can be barely noticeable in the pictures. Hence its size must be determined from fluorescence angiography, but this image does not have any relation to the images generated by the slit lamp even though it is from the same eyeball. Reasons for this discrepancy include the use of different optics, different viewing angles, etc. In any case, whether the treatment is determined from the slit lamp picture or from the angiography, the error made by the calculation of the beam spot size is significant and typically exceeds 200%.

For this reason, not only is the treatment zone illuminated, but healthy zones in the eye are also illuminated. This can lead to the destruction of important blood vessels resulting in a reduction of eyesight. The present invention provides a solution to this.

State of the art methods apply a treatment beam source which generates a round intensity profile, which is either of a gaussian or near gaussian shape or of a so-called top hat structure which is characterized by a very sharp edged rise and fall of the intensity at the edges and a near constant intensity in the middle. In either case, the created variable spot size is of a round shape. Obviously, the shape of the treatment zone is not necessarily round. In the most simple case, it has an oval or a slit form, but typically the shape of the area needing treatment is of a more complicated structure. Since there is already a very large error in determining treatment areas using state of the art devices and methods to perform fundus treatments, there has been no need for generating a better overlap of the treatment zone and the treatment beam spot area. This is addressed in the present invention, which can provide variably shaped treatment beam spot areas, now that the treatment beam is more accurately formed and projected onto the treatment zone.

Another general problem in laser based fundus treatment is movement of the eyeball during treatment. From clinical studies the optimal illumination times are known, but during treatment it must be assured that the treatment zone is illuminated for this period. In the state of the art, operators view the treatment area in real time by means of a fundus viewing ocular. The device further provides means for the operator to switch the treatment beam source on and off and thus control the beam source such that the beam source is on only if the treatment zone is within a certain region. This method is a potential source of inaccuracy, because both the beam and the treatment zone are barely visible during the treatment. The present invention provides a solution to this and the several problems identified above.

OBJECTS AND SUMMARY OF THE INVENTION

It is an object of the present invention to provide a method and a device for accurately adjusting a laser beam spot size to the treatment area for each specific eyeball.

It is another object of the present invention to determine the exact shape and size of a treatment zone without the need for an operator-specific method, with less dependence on an operator for defining a treatment area.

It is another object of the present invention to determine the exact shape and size of the treatment zone from digital processing of a previously generated image generated with one diagnostic method and a native fundus image generated by the same or another diagnostic method for live observation.

It is still another object of the present invention to provide a method and device to exactly determine “forbidden areas” as well as treatment areas as to control the treatment beam appropriately.

It is yet another object of the invention to provide a device and method to achieve a significantly better overlap of the treatment zone and the treatment beam spot area.

It is a further object of the present invention to provide a device allowing accurate viewing and means for automatic switching of the beam source depending on the eye movement as well as a device capable of adjusting the spot area in real time according to the eye movement.

It is a still further object of the present invention to provide a system and a method to control automatically or semi-automatically the treatment beam for different photocoagulation (green laser), TTT treatment and photochemical (PDT) treatment methods.

It is another object of the present invention to provide a device capable of carrying out different photocoagulation and photochemical treatment methods alone or in combination.

It is yet another object of the present invention to control the treatment beams to treat the same or different areas with different photocoagulation and photochemical methods.

Briefly stated, the present invention provides a system and method to accurately treat sites on an eye's retina employing computer based image generation, processing and central control means in conjunction with diode laser sources and optical fibers. The system and method accurately determine geometry of a treatment zone of a specific eye's fundus and adjust the shape, size and position of a treatment beam to irradiate the treatment zone with minimal coverage of adjacent well tissue. The treatment zone is accurately determined with image processing such as matching or alignment of two distinct images. In a preferred embodiment, a previously generated image taken with angiographic data in relation to a native fundus image generated by a slit lamp. This information is integrated with information on the treatment beam characteristics to better match treatment beam coverage with minimal overlap with healthy areas of the fundus, by preventing irradiation of “forbidden areas” which would be severely damaged by the irradiation. The present invention is also capable of carrying out different photocoagulation and photochemical treatment methods at different wavelengths, power energies and other treatment parameters. Additionally, preferred embodiments also have the ability to automatically track eye movement, switch the beam source depending on eye movement, and adjust the beam spot area in real time.

The above, and other objects, features and advantages of the present invention will become apparent from the following description read in conjunction with the accompanying drawings, in which like reference numbers in different drawings denote like items.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates the general setup of a device for treatment of an eye's fundus. [0030]
FIG. 2 illustrates integration of digital image processing means into a device for fundus treatment. [0031]
FIG. 3 shows a variable aperture imaging method to obtain a sharp edged intensity profile of variable beam spot area on a retina. [0032]
FIG. 4 illustrates implementation of a scanner system with suitable optical imaging means in order to obtain a sharp edged intensity profile of arbitrary beam spot area on a retina. [0033]
FIG. 5 illustrates implementation of an optical system including a two dimensional movable beam source in the device in order to obtain a sharp edged intensity profile of arbitrary beam spot area on a retina. [0034]
FIG. 6 contains an alternative device for the displacement of the laser beam to treat a two dimensional treatment area. [0035]
FIG. 7 illustrates the use of a telescope to vary beam spot size into the device.[0036]

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The accuracy of the treatment of the fundus of an eye can be drastically enhanced by the combination of diagnostic means with a therapeutic setup. The therapeutic setup consists of a light source, preferably a fiber coupled diode laser and a suitable optical system which allows the user to vary the spot size generated on the retina. The diagnostic device is preferably a slit lamp with an additional optical setup to allow direct fundus viewing through an eyepiece and simultaneous generation of a digital image of the fundus referred to as native fundus image. The digital image of the fundus is created by a computer based image processor and an image generation device which is preferably a CCD camera. The size of the treatment zone can be determined and electronically processed in the following manner: The treatment beam spot area is varied by an adjusting optical system provided by this invention. The reference digital image of the fundus is generated with a simulation of the treatment beam (aiming beam) on the retina whereby the spot size of the treatment beam is predetermined by the optical system by switching the optics to a basic position. At this basic position the parameters of the spot size of the treatment or aiming beam are known independently of further e.g. magnification changing optical means like e.g. eye pieces. Moreover, from this known spot size the image is calibrated and the treatment area can be calculated exactly. Moreover, a green aiming beam emitted by a secondary light source provides a better and sharper image for the practitioner and means a reduced irradiation of the patient thereby avoiding undesired side effects. From these two images it is possible to adjust the treatment beam spot area to the actual treatment zone size. [0037]
Further, if the treatment zone is not sufficiently clear in the generated diagnostic native fundus image, it is an object of the invention to include a digital previously generated image generated by means of another diagnostic method such as fluorescence angiography. Because the slit lamp generated image often is not sufficient to determine the tumor or AMD affected area, the angiography imaging often is a necessary prerequisite for successful treatment. Moreover, it is a subject of the present invention to align the previously generated angiography image, which is characterized by an extremely high quality, with the native fundus image obtained by the diagnostic means in the claimed treatment device and determine the necessary treatment beam spot size from the treatment zone area that is visible in the previously generated image obtained by fluorescence angiography. [0038]
In a preferred embodiment the above-mentioned screening, image processing and controlling means are used to control the short-pulse photocoagulation treatment. This treatment is preferably carried out with a green laser (532 nm), but other wavelengths ranging from 514 to 810 nm are used. This method is useful for coagulation of damaged vessels or re-welding of the retina to the eye background. Due to the high power densities of about 80 W/cm[0039] ²and the resulting damage to tissue, the treatment beam is not to be used within the macula (“forbidden area”). Consequently, for this treatment the determination of the treatment area and the determination of a “forbidden area” is essential, together with control of the treatment beam.
In another preferred embodiment, the above mentioned screening, image processing and controlling means are used in long-pulse photocoagulation or TTT devices and methods. Preferred applications of these treatments are tumor therapy (810 nm, ˜500-[0040] 800 mW/cm²) and AMD therapy (810 nm, 7.5 W/cm²). In all cases the effectiveness as well as the security of these treatment methods are significantly increased by the accurate determination of the treatment areas, online image processing and quality control means provided by the present invention.
In yet another preferred embodiment, the above-mentioned screening, image processing and controlling means are used in photodynamic therapy (PDT). In this treatment, a photosensitive drug (photosensitizer) is introduced into the patient's bloodstream, and after a certain period is activated at the treatment sites by localized irradiation. The substances are activated after a period of 15 min to 20 min by long-pulse, low energy radiation (600 mW/cm[0041] ²). The use of an aiming beam provided by this invention is especially advantageous in PDT to reduce side effects, since the slit-lamp light normally used includes a significant range of wavelengths which are able to activate the photosensitive agent at unwanted sites.
In a further preferred embodiment, different treatment methods at different wavelengths, power densities and other parameters are combined to enhance the effectiveness of the treatment. The treatment of the same area with different methods may be advantageous as well as treatments of different areas with different methods. In all cases it is essential to accurately determine the treatment areas and control the treatment beams by means of the present invention. For example, in some cases of AMD, an effective treatment would be the initial application of TTT to close feeder vessels by photocoagulation, followed by PDT to further treat neovascularisation in the same or other areas. This combination of methods may also be useful in tumor treatment by first coagulating feeder vessels of the tumor with a green laser and then destroying the tumor tissue with TTT. The combination of green Laser and PDT might also be useful for the treatment of retinal diseases caused by diabetes. [0042]
All treatment methods mentioned above can be either implemented automatically, require manual settings by the operator, or be realized in a combination. Several methods to generate a variable beam spot area on the retina are also subjects of the invention. [0043]
The device described in the present invention has several advantages for the practitioner. First, the user is able to safely determine the treatment area and the “forbidden areas” where irradiation would be harmful. Second, the user is able to combine different methods with a single device and accurately control all methods. The ability to use different treatment methods in a single device results in cost and space saving over the prior art, which require a number of devices to deliver different treatments. [0044]
FIG. 1 illustrates a preferred embodiment of the present invention, including all elements that are necessary to perform treatments of age related macular degeneration and other diseases by optical means. For reasons of simplicity, only the basic elements of patient's [0045] eye 1 are included in the figure, which are retina 2 and lens 3. Optical radiation enters the eye via lens 3 and forms an image on retina 2. For successful laser treatment, contact lens 4 is placed at the cornea of the patient's eye to minimize possible eye movement and enable the laser radiation to enter the eye without damaging the cornea and with enhanced imaging properties. For reasons of simplicity the complex optical system present in contact lens 4 is not shown. Contact lens 4 has a certain refractive power as is well known in state of the art laser treatment of the retina. Several different kinds of radiation are imaged on retina 2. One example is laser radiation 5. This radiation is originated by laser system 14, which is preferably a diode laser. The present invention bears one or more of these primary irradiation sources so as to be able to emit irradiation of one or more different wavelengths for the use in one or more different treatment methods. Radiation 5 is coupled into optical fiber 13, which has a well defined core diameter and numerical aperture. Optical fiber 13 is a preferred element, because it simplifies the device and helps to shape treatment radiation 5 to the desired “top-hat” form characterized by very sharp rising and falling intensity profiles at the edges and a plateau-like near constant intensity elsewhere. Radiation 5 emitting from the fiber end is collimated by an optical system and optionally imaged to obtain a desired beam profile. None of these optics is a necessity; in fact quite a number of possible systems with an arbitrary number of lenses or even without any lenses can be used depending on the targeted problem.
[0046] Beam source 14 has another feature: it contains an optical system that allows for coupling the radiation from a secondary light source into optical fiber 13. This secondary light source preferably has a different wavelength and typically has a much lower optical power than the treatment source. Due to the retina's optical characteristics, the treatment beam is sometimes hard to observe, and this additional light source increases visibility and thus drastically increases the viewing possibilities. Using viewing sources at different wavelengths resolves this viewing problem, because the wavelength can be chosen in order to obtain the maximum viewing quality. Optional viewing radiation 16 is preferably imaged via optical system 10 along with treatment beam radiation 5 itself. In order to better represent the optical system in FIG. 1, the secondary radiation is illustrated on a different optical path parallel to the primary radiation, though it can in general also take the same path depending on the optical setup.
Both types of radiation pass through [0047] beam adjustment device 12. Secondary radiation 16 creates image 11 on the retina, which does not necessarily coincide with image 15 created by the treatment radiation itself. Nevertheless, since the radiation properties are known, it is possible to determine the treatment image from the secondary image.
The design of [0048] optical system 12 is a subject of the invention and is now described in detail. Common to all these embodiments is that adjustments by optical system 12 are not static, but are variable so as to create variable images on retina 2 that have varying beam spot areas. It is common in laser based eye treatment methods to allow simultaneous inspection of retina 2. Therefore, inspection means in the form of a slit-lamp are included in the device. In its simplest form, a slit lamp consists of light source 8 with a collimating optical system generating illumination radiation 7 that has suitable optical characteristics. Mirror 9 is located at 45 degrees with respect to the optical axis. The purpose of mirror 9 is to image illumination radiation 7 into the eye. The illuminated area can be viewed along mirror 9 with back propagating image radiation 17 passing through the slit of mirror 9 and entering optical system 18, thereby fulfilling imaging purposes. Radiation 7 is chosen such that it can pass through dichroitic mirror 6. Mirror 6 is highly reflective, but not totally reflective, for treatment radiation 5 and optional secondary radiation 16. Thus, small portions of both treatment radiation 5 and secondary radiation 16 returning from retina 2 can pass through the mirror and contribute to the viewing means. Additional filters 19 can be optionally included in the path of viewing radiation 17 in order to enhance the quality or observe only selected kinds of radiation. Beam splitting means 20 is placed in the general optical system behind primary optical system 18. A part of radiation 17 is mirrored into first secondary optical system 23, which creates an image on the detector area of digital image generation means 24, preferably a CCD camera. Another set of filters 19 can be applied in the path. The other part of radiation 17 is propagated through secondary optics 21 and through ocular 22 for direct viewing by the operator, preferably a physician.
As described earlier, the state of the art suffers from several deficiencies that basically originate from the fact that the area of the treatment zone cannot be determined accurately. Thus all treatment beam spot size variation methods are rudimentary and produce an error up to 600%. [0049]
One significant innovation of the present invention has already been mentioned above: beam area generation means [0050] 10 are of a more sophisticated nature than is found in the prior art. FIG. 2 shows additional elements that are part of the present invention to allow highly accurate treatment of the fundus of an eye. A central processing unit, preferably a PC in a desktop or in an embedded form is used to both control the incoming data from viewing devices 24 and the variable beam area generating optical system 12. This unit is programmed to control the adjustment as well as parameters including wavelength, power density, and treatment duration for one or for combined treatment methods. One or more display units 27 are connected to processing unit 25 to display the viewing data, display external data and perform operations in order to optimize the treatment procedure. To minimize the error in the above treatment, the present invention is used in a three step method. First, the treatment area is determined from images supplied by the different optical viewing devices which are set in correlation with each other by the image data processing. Second, based on these data the beam spot area is adjusted in the same relative way. Third, the treatment beam is imaged to the retina. This method is a significant improvement over prior art methods in which the practitioner determines the treatment area and adjusts the treatment beam based on fluorescence images generated under different conditions with a different optical device and which are not correlated with the optics of the laser treatment device.
One method for accurately determining the treatment area consists of the following. A digital image using slit-[0051] lamp device 9 and digital image generation means 24 is taken. Another digital image, the reference image, is taken with the retina irradiated preferably by secondary light 16 with the optical system 12 being responsible for setting up the treatment beam area on the retina in a pre-determined basic position. Alternatively, the treatment beam light itself can be used, but at significantly lower radiation power. However, due to reasons of visibility explained above, the use of a secondary light source is preferred. If PDT is used as treatment method it is especially advantageous not to use the slit lamp as image generating means but an aiming beam as provided by this invention, since the light of the slit lamp contains a significant part in range of wavelengths which activate the photosensitizer and lead to undesirable side effects. From this image generated with light 16, the spot size of treatment beam 5 can be precisely calculated in relative coordinates to the slit lamp generated native fundus image. Further, a digital image without treatment radiation 5 or secondary radiation is taken within a time interval short enough to assure that the eye did not move. Alternatively, a true real time online image can be taken using either digital image filtering means or using real filters and more than one digital image recording device. From this image the treatment zone as well as the “forbidden zones” may be determined with sufficient accuracy. If so, the operator marks the treatment zone with a simple software tool and the computer calculates the accurate size and coordinates. Applying a simple method, the operator can then use this data to manually adjust the beam area spot size with suitable optical system 12, which may be guided by electronic aids such as acoustical or optical signals. An even more accurate method is to have central processing unit 25 control optical system 10. The treatment beam parameters are also provided by central processing unit 25. The operator can now use manual positioning means 28 to locate the beam spot area center to a predetermined position within the treatment zone, preferably the center or one of the edges. As in the prior art, he can stop and start the treatment beam with a second external control, preferably a foot-piece, and simultaneously inspect the fundus in order to decide if the treatment area and the treatment beam are aligned or if this alignment has been disturbed by eye-movement. A significant difference and advantage over the state of the art is that the viewing can also be done via the digital image generated in real-time and illustrated on display unit 27. Digital image processing can enhance the image quality, and electronic image detection means 24 is more specifically sensitive to the applied wavelengths.
Another method for accurately determining the treatment area with the present invention is to align the native fundus image generated by the slit-lamp means to a diagnostic previously generated image generated by means of fluorescence angiography. Slit lamp generated images are generally of medium quality and, depending on the status of the disease and the specific eyeball, the treatment zone can hardly be seen or may not be determined with sufficiently high accuracy. Therefore a digital previously generated angiography image is loaded onto central processing means [0052] 25 and displayed on display device 27. As before, simultaneously or quasi simultaneously a slit lamp native fundus image is taken with and without the treatment beam spot and also displayed for the operator. From a minimum of two characteristic points like blood vessel crossings which may be marked by the operator himself, the central processing unit aligns the two images, since they are in general of different form, because the optics or the eye position may vary. The operator further marks the treatment zone in the angiography image, which can be done with high accuracy. These coordinates are then calculated back to coordinates of the slit lamp native fundus picture and the system is able to calculate how optical system 12 responsible for the treatment beam spot generation must be adjusted in order to achieve high overlap accuracy. As described above, the adjustment can be performed manually with possibly electronic aids or fully automatically. In a preferred embodiment the complete adjustment, including the positioning of the beam spot to the treatment area, the treatment process and the treatment control is performed automatically by the central processing unit on the basis of a real-time viewing of the retina with the digital image processing means.
FIG. 3 illustrates a preferred embodiment for [0053] optical device 12, which is responsible for the generation of the treatment beam area. The treatment beam is produced by primary beam source 14 and is preferably coupled into optical fiber or light guide 13 where it is shaped to the desired top hat intensity profile. The beam can then be transported by simple means from primary beam source 14 to the treatment device, allowing the beam source to be spatially separated from the patient, which is of particular importance for laser sources due to safety requirements. From there, primary radiation 5 illuminates aperture 31. The radiation can illuminate aperture 31 either directly or by an imaging means, such as a telescope, to produce a fixed spot on aperture 31. Optimally, radiation 5 can be collimated in order to minimize the divergence angle. Aperture 31 cuts a defined section from said beam. This cut has, apart from diffraction limits, sharp intensity edges, which is of great advantage to the treatment process in that it assures that all parts of the treatment zone are irradiated with the same energy. Aperture 31 is adjustable via mechanical means such as micrometer screws that are moved by the operator directly or via electromechanical means 34 such as step motors or piezo actuators. Means 34 can be controlled directly by the operator with suitable control devices or by central processing unit 25 that is connected with means 34 via interface lines 35. More than one aperture may be included within the setup, illustrated by additional aperture 32 in FIG. 3. Additional apertures can be controlled in the same manner as the primary aperture and serve various purposes. One such purpose is the generation of a two dimensional irradiation surface on the retina which is of higher complexity than the simple circle preferably generated by single aperture 31. For example, the combination of a circular aperture with a slit aperture allows near-oval irradiation spots or two slit apertures allow rectangular forms. In a preferred embodiment the whole aperture unit is exchangeable, allowing the operator to choose a certain combination in order to adjust the treatment beam image to the treatment area determined from the diagnostic fluorescence angiography image. As already mentioned the basic position of the system generating the reference image is common to all the optical systems used independently of different magnification characteristics. In the case of the aperture based solution to the adjustment of beam spot size to treatment zone size, the basic position of electromechanical dislocation means 34 is directly related to the size of apertures 31, 32, and any additional apertures. This aperture is first illuminated with secondary beam 16 and the radiation passing the aperture propagates to the eyepiece or is optionally imaged via optical system 33. The image of the aperture on the retina is then recorded and digitized. This digital image is one of the basic images mentioned above to perform the calibration. Therefore, secondary beam 16 must be coupled into the propagation path of primary radiation 5. This is done in a unique and well known way in order to have a well defined system of coordinates to compute the shape and size of image 15 from secondary beam retina image 11. In a preferred embodiment, secondary beam 16 is already coupled to optical fiber 13 together with the treatment beam. The operator can then use primary beam 5 to chose the exact position of the treatment zone and start the process. This is performed as described above utilizing the means illustrated in FIG. 2.
FIG. 4 illustrates a more advanced system for the generation of the treatment beam area on the retina. State of the art methods suffer from the deficiency that they produce round spots since optical fibers, laser profiles or lamp emitted radiation generally produce round spots. These spots are then shaped and imaged to the retina. The new method illustrated in FIG. 3 and described above is already a significant innovation over the state of the art, since it allows shapes other than round profiles. Additionally, the treatment beam is kept at small sizes and thus there is no longer a requirement for a rectangular top hat intensity profile. However, the treatment zone usually has a much more complicated form. In the prior art, the treatment zone could not be determined with sufficient accuracy, hence there was no need for the generation of an accurate treatment beam area. By the methods of this invention the treatment zone becomes well known, hence the mechanisms to illuminate said treatment zone can be enhanced in the same degree. FIG. 4 basically consists of the components described above, but adjusting [0054] optical system 12 is embodied as a scanning device. In its most basic form a scanner contains two movable mirrors 36 and 37 positioned in an orthogonal way. The angle relative to the optical axis of each mirror is adjustable in one dimension, thus the beam can be arbitrarily positioned on a two dimensional surface according to their orthogonal position by independent angle variation. This surface can further be imaged onto the retina via contact lens 4 and the eye's lens. Source 14 can be collimated, optionally be expanded to the desired diameter with suitable optical system 10 and then be directly imaged by the scanning means.
The eye lens and the original beam diameter hitting the eye lens are responsible for the size of the beam spot on the retina, on which the beam delivered by the treatment beam spot is dependent on the beam diameter and divergence angle when it hits the contact lens and on the contact lens itself. By varying the contact lens and the beam properties by means of adjustable [0055] optical system 10 the beam spot on the retina can be varied accordingly. For use with a scanner the beam is of relatively low power and small size. If the scan velocity is chosen to be sufficiently large, each spot on the treatment zone is impinged by a sufficiently large number of photons for an optimal treatment process.
To generate a true image of the treatment zone determined by use of the methods described above, two ways can be followed. The first consists of the generation of a rectangular image and switching the primary beam source on and off sufficiently fast, hence simply no intensity is emitted if the scanner is positioned at a point out of the treatment zone and the laser is on if the scanner is positioned at a point on the treatment zone. Hence even non connected treatment zones can be mapped accurately. [0056]
The second method is to operate the scanner in an asynchronous mode with interruption. [0057] Mirrors 36 and 37 do not just map a rectangle, they rather map the concrete form of the treatment zone. This enhances the scanning efficiency and lowers the requirements of the switching velocity of primary beam source 14. However, the requirements of the scanner deflection properties rise.
Scanner deflection can be implemented by various methods, two common methods include the use of galvanometric driven mirrors and piezo actuator driven mirrors. [0058]
Alternatively, instead of two orthogonal one-dimensional deflecting mirrors, a single two-dimensional deflecting mirror can be used. A scanner system can be even of higher complexity. Today, micro-mirror devices are commercially available, for example by Texas Instruments, Inc. of Houston, Tex. which consist of a two dimensional array of micro mirrors. These devices are able to produce pixel based 2-dimensional image structure which can be used in display technologies, in micro machining and for applications in medicine. A device of this type is included as the basic element of adjusting [0059] optical system 12, optionally combined with suitable optical elements to create optical images which fulfill all the requirements given by the micro-mirror device and the treatment zone. The micro-mirror device is directly controlled by central processing unit 25. The image created directly propagates via the optics and contact lens 4 to the retina.
An equivalent effect of the micro mirror method can be achieved using liquid crystal devices and polarizers, similar to the use of liquid crystal devices in printing, display and lithography applications. [0060] Optical system 12 would then contain an optical setup which is a liquid crystal modulation device which allows generation of an image formed by a sufficiently large number of pixels that matches the treatment zone. It is obvious that any image generation means can be included in a treatment setup to generate the treatment zone illumination beam area.
The optics further can be positioned externally by the operator, for example, by using positioning means [0061] 28. In particular, said positioning to treatment zone is enhanced by using the secondary beam source as an aiming beam and using the digital image recording and processing means described above.
The use of a scanner system as described only makes sense if it is operated with sufficiently fast driving electronics and controlled by a computer based system. The inclusion of a system of this type and the connection of all variable elements to the central processing unit is also a subject of the present invention. [0062]
FIG. 4 shows another innovative method for the generation of a variable image on the retina. From the point of the operator and the patient, this method provides an equivalent interface for the treatment itself and the result will also be comparable to the results obtained by using scanner methods. In fact the scanning facility is maintained, but in this case secondary [0063] light source 16 itself, if directly included in the treatment setup, or the emitting end of fiber 13 if the beam source is external and its produced radiation is transported to the treatment device by fiber 13, is moved along a special path. This movement can, as with the scanning method described before, follow a complicated path directly or follow a rasterized rectangle. Primary light source 14 is switched according to the treatment size image requirements. To generate the movement of, for example, the fiber end, a two-dimensional scanning unit can be constructed either mechanically, electro-mechanically by the application of piezo actuators or by a combination of these. In FIG. 5, fiber 13 is connected to mount 36. Mount 36 is fixed on two dimensional displacement unit 40. Actuators 41, preferably piezo actuators, cause the appropriate movements and are connected with central processing unit 25 by connection lines 35. Since aiming beam 16 produced by the fiber is preferably transported by said fiber it follows the same contour as treatment beam 5 and can thus be still used for all purposes mentioned above. The optical system images the plane, in which the fiber end moves to the retina. Optionally, the optical system can be varied automatically by central control unit 25 or be exchangeable in order to achieve different imaging relations.
FIG. 6 illustrates another element which can be implemented in the optical path to achieve the desired beam displacement. [0064] Incoming treatment beam 5 passes parallel plate 42 optionally coated dielectrically in order to minimize losses. This plate is mounted so that it is movable in relation to one reference point located on cylinder 47. The plate can now be rotated relative to this reference point to a certain angle by actuator 49. Actuator 49 can be a simple stepper or, preferably a piezo actuator, which is in suitable contact with parallel plate 42. In particular it must allow a certain linear movement of the actuating point. Because of this angle, incoming beam 5 is displaced by a certain distance hence outgoing beams 45 and 46 are parallel to the incoming beam, but displaced by different distances according to the angle at which the plate is positioned within the beam. If the plate is in the position marked by feature 43 it creates a smaller displacement, producing beam 45, than if it is in the position marked by feature 44, producing displaced beam 46. This displacement is uniquely given by a mathematical relation between the displacement and the angle and can hence be controlled accurately. The two dimensional displacement can be obtained either by the use of two orthogonal devices each producing a displacement in one direction or a single plate, which has one fixed reference point and two orthogonal variable points. For this displacement unit all optical and electronic features described above can be used.
FIG. 7 illustrates another embodiment of the treatment optics. Primary [0065] light source 14 creates treatment radiation 5, which is preferably coupled into optical fiber 13 and transported to the treatment device. Radiation 5 is transported together with secondary radiation 17 which serves as aiming beam and preferably has a different wavelength. The output 5 and 16 from fiber 13 is preferably collimated by optical system 10 and then coupled into optical system 52, which plays the role of adjusting optical system 12 in prior embodiments. System 52 consists of the optical module of a commercial video camcorder, which is available as a component, as for example the Sony ELI Series. In their original application these modules are intended to generate images on a camera chip for different object distances, which is basically equivalent to the purpose required for the treatment of the fundus of an eye. The optical states of module 52 can be varied electronically through interface 35 and central processing unit (not shown), which is preferably a PC. The reference image used for the calibration of the angiography to the native fundus image is recorded at a fixed position of the video module and with the data obtained from the image calibration. The correct state is chosen in order to generate a well defined treatment spot on the treatment zone. The principal treatment features are equivalent to the other embodiments described above. This method can in particular be combined with the aperture method which enhances the performance because it allows other than round profiles, the aperture creates top hat intensity structures if desired and operated far from the diffraction limit and the process can be implemented electronically and thus be controlled completely by a central processing means.
Having described preferred embodiments of the invention with reference to accompanying drawings it is to be understood that the invention is not limited to those precise embodiments, and that various changes and modifications may be effected therein by one skilled in the art without departing from the scope or the spirit of the invention as defined in the appended claims. [0066]

Claims

What is claimed is:

1. A system for improved, accurate treatment of an eye's fundus comprising:

at least one optical setup for irradiating an eye's fundus with light emitted by a primary light source;

at least one device to take optical images of said fundus;

at least one secondary light source to generate a reference digital image on an eye's retina at a predetermined basic position of a treatment beam imaging optical system;

at least one computer based setup for controlling and for digital image processing to accurately determine a treatment zone;

means for simultaneous generation of a native digital image of said fundus;

a unique marking of said treatment zone on said digital fundus image, creating a digital reference image;

an adjustment means; and

wherein within one device, through said digital image processing and said adjustment means, said at least one optical setup for irradiating said fundus is adjusted to provide optimal irradiation characteristics to perform an improved, accurate treatment.

2. The system for improved, accurate treatment of an eye's fundus according to claim 1, wherein said at least one optical setup is capable of emitting different wavelengths with variable power densities to be applied in different photocoagulation and photochemical treatments.

3. The system for improved, accurate treatment of an eye's fundus according to claim 2, wherein said different photocoagulation and photochemical treatments are selected from the group consisting of short-pulse coagulation, long-pulse coagulation, green laser, transpupillary thermotherapy and photodynamic therapy.

4. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising:

means to uniquely mark “forbidden zones” which are not allowed to be irradiated on said digital image of said fundus; and

means to make a digital reference image used for adjustment of said treatment optical system to avoid irradiating said forbidden zones with said at least one primary light source.

5. The system for improved, accurate treatment of an eye's fundus according to claim 2, further comprising means to combine said different treatments.

6. The system for improved, accurate treatment of an eye's fundus according to claim 2, further comprising means to automatically and semi-automatically control said at least one treatment beam for said different photocoagulation and photochemical treatments.

7. The system for improved, accurate treatment of an eye's fundus according to claim 6, further comprising means to controllably apply said at least one treatment beam of said different treatments to a same area, whereby said different photocoagulation and photochemical treatments can be applied simultaneously or consecutively within a single treatment.

8. The system for improved, accurate treatment of an eye's fundus according to claim 6, further comprising means to controllably apply said at least one treatment beam of said different treatments to different treatment areas.

9. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising:

means for loading, displaying and processing a digital image of said fundus provided diagnostically by means of fluorescence angiography;

means for generating a native digital image of said fundus; and

means to align said native digital image by suitable mathematical algorithms with said loaded previously generated digital image generated by fluorescence angiography means to obtain a unique correlation between coordinate systems for these two images.

10. The system for improved, accurate treatment of an eye's fundus according to claim 9, wherein said means to align is an automatically operating pattern recognition means.

11. The system for improved, accurate treatment of an eye's fundus according to claim 9, wherein said means to align said native and previously generated images is at least two reference points manually marked in each of said images, and said images are said native fundus digital image and said loaded previously generated digital image from said diagnostic fluorescence angiography.

12. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising:

at least one variable aperture;

an optical system to image said aperture onto said treatment zone on said retina; and

an additional optical system to image said treatment beam onto said variable aperture.

13. The system for improved, accurate treatment of an eye's fundus according to claim 12, wherein said treatment beam has a radiation intensity profile with a rectangular shape otherwise known as a top hat shape.

14. The system for improved, accurate treatment of an eye's fundus according to claim 13, wherein said image generated on said retina has a polygonal shape which is selected from the group consisting of substantially circular, substantially oval, substantially rectangular, and preferably square.

15. The system for improved, accurate treatment of an eye's fundus according to claim 13, further comprising at least one additional aperture, having a different shape from said variable apertures, which can be sequentially applied to create images on said retina of shapes more complicated than simple polygons.

16. The system for improved, accurate treatment of an eye's fundus according to claim 15, wherein said variable and additional apertures are independently variable and can be adjusted to a desired size by a method selected from the group consisting of manual, manual with electronic aids, electrochemical, and completely automatic.

17. The system for improved, accurate treatment of an eye's fundus according to claim 1, wherein said at least one primary light source is selected from the group consisting of a laser, a diode laser, a luminescent diode, and at least one optical fiber whose opposite end is coupled to at least one laser.

18. The system for improved, accurate treatment of an eye's fundus according to claim 1, wherein said secondary light source operates at a wavelength different than that of said primary light source and said secondary light source is selected from the group consisting of a laser, a diode laser, and a luminescent diode.

19. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising:

at least two variable orthogonal mirrors;

at least one imaging optical system and an automatic primary beam switch; and

scanning means, wherein these components adjust said treatment beam create a two dimensional image on said treatment zone on said retina.

20. The system for improved, accurate treatment of an eye's fundus according to claim 19, wherein said imaging optical system is variable and preferably replaceable.

21. The system for improved, accurate treatment of an eye's fundus according to claim 1, wherein said adjustment means further comprises:

a micro-mirror device where each mirror can be addressed individually; and

at least one optical imaging system.

22. The system for improved, accurate treatment of an eye's fundus according to claim 1, wherein said adjustment means further comprises:

a liquid crystal device where each pixel can be addressed individually including a polarizer and an analyzer; and

at least one optical imaging system.

23. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising:

at least two variable, linear, orthogonal-arranged position devices;

an automatic primary beam power switch; and

whereby scanning an end of an optical fiber that transfers said treatment beam with said position devices creates an arbitrary two dimensional region on said retina.

24. The system for improved, accurate treatment of an eye's fundus according to claim 23, wherein said position devices comprise piezoelectric elements.

25. The system for improved, accurate treatment of an eye's fundus according to claim 23, further comprising:

an optical system;

a contact lens on a cornea of an eye to be treated to image said two dimensional region onto said retina;

wherein a shape of said two dimensional region generated on said retina conforms exactly to a shape of said treatment zone; and

wherein said optical system is variable and preferably replaceable.

26. The system for improved, accurate treatment of an eye's fundus according to claim 12, wherein said optical system to image said aperture onto said treatment zone comprises at least one lens.

27. The system for improved, accurate treatment of an eye's fundus according to claim 12, wherein said optical system to image said aperture onto said treatment zone comprises an optical module of a commercial camcorder.

28. The system for improved, accurate treatment of an eye's fundus according to claim 1, further comprising at least one contact lens positioned on a cornea of said eye, and wherein said retina can be observed directly via an eyepiece.

29. An improved, accurate method of treatment of an eye's fundus, using an optical treatment system, preferably with a slit lamp assembly, comprising the steps of:

a. generating a treatment beam from a primary light source;

b. generating a digital reference image preferably by means of fluorescence angiography, using a secondary light source, on an eye's retina at a predetermined position of said treatment beam's imaging optical system, wherein said secondary light source preferably operates at a different wavelength from said primary light source;

c. controlling and processing said digital reference image by at least one computer to accurately determine a treatment zone;

d. simultaneously generating a native digital image of said fundus;

e. uniquely marking said treatment zone onto a corresponding region of said native digital image of said fundus; and

f. adjusting said treatment beam and said optical treatment system to have said treatment beam cover said treatment zone and optimally irradiate said treatment zone.

30. The improved, accurate method of treatment of an eye's fundus according to claim 29, further comprising the steps of:

g. uniquely marking “forbidden zones” which are not allowed to be irradiated on said digital reference fundus image; and

h. adjusting said treatment beam and said optical treatment system to have said treatment beam avoid said forbidden zones.

31. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said method of treatment is a combination of different photocoagulation and photochemical treatments;

wherein said photocoagulation treatments are chosen from the group consisting of short-pulse photocoagulation and long pulse photocoagulation; and

wherein said photochemical treatments are chosen from the group consisting of green laser, transpupillary thermotherapy, and photodynamic therapy.

32. The improved, accurate method of treatment of an eye's fundus according to claim 31, wherein said different photocoagulation and photochemical treatments are controllably applied to selectively switch between simultaneous and consecutive treatment of a treatment area within a single treatment.

33. The improved, accurate method of treatment of an eye's fundus according to claim 31, wherein said different treatments are controllably applied to different treatment areas.

34. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said adjusting said treatment beam is accomplished by a method selected from the group consisting of manual completion by an operator, assistance by an electronic means, preferably with optical or acoustical signals, and full automation.

35. The improved, accurate method of treatment of an eye's fundus according to claim 29, further comprising the steps of:

d(1). aligning said native digital image of said fundus with said image of said treatment zone by applying suitable mathematical algorithms to correlate between coordinate systems for these two images, wherein said aligning is accomplished by one of the following methods: an automatically operating pattern recognition scheme, and manually marking at least two reference points in each image;

36. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said step of adjusting said treatment beam is accomplished by illuminating and imaging at least one variable aperture having an optical system onto said treatment zone on said retina and imaging said treatment beam onto said variable aperture and onto said retina to create pre-selected polygonal shapes.

37. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said step of adjusting said treatment beam is accomplished by sequentially illuminating and imaging at least two apertures having different shapes to generate said image on said retina in more complicated shapes than simple polygons.

38. The improved, accurate method of treatment of an eye's fundus according to claim 37, wherein said apertures are varied independently of each other and adjusted to a desired size by a method selected from the group consisting of manual, semi-automatic and automatic means.

39. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said step of adjusting said treatment beam is accomplished by scanning with at least two variable, linear, orthogonal-arranged devices and using an automatic primary beam power switch to create an arbitrary-shaped two dimensional region substantially equivalent to said treatment zone.

40. The improved, accurate method of treatment of an eye's fundus according to claim 39, wherein said scanning of said treatment beam over said treatment zone irradiates each point in the treatment zone for a predetermined period of time.

41. The improved, accurate method of treatment of an eye's fundus according to claim 39, wherein said step of adjusting said treatment beam is accomplished by a method selected from the group consisting of manual adjustment by an operator, assistance by electronic means, preferably with optical or acoustical signals, and fully automatic adjustment.

42. The improved, accurate method of treatment of an eye's fundus according to claim 29, wherein said secondary light source operates preferably at a green wavelength, and wherein said secondary light source produces an image containing at least one shape chosen from the group consisting of a ring and a cruciform.

43. The improved, accurate method of treatment of an eye's fundus according to claim 36, wherein an image of said treatment beam is positioned manually on said retina, preferably being positioned there by at least one secondary target spot and wherein said native digital image of said fundus is generated in real time, and said position of said treatment spot area is determined electronically and transformed into said coordinate system of said diagnostic fluorescence angiography and displayed thereon.

44. The improved, accurate method of treatment of an eye's fundus according to claim 43, wherein in real time said position of said treatment zone is determined and said treatment light source is appropriately switched on and off;

wherein said native image of said fundus containing said spot of said treatment beam and said image generated diagnostically by fluorescence angiography means are digitally processed, superimposed and presented on a display device; and

wherein in real time said position of said treatment zone is determined and said treatment beam spot is positioned in real time according to said treatment beam spot position.

45. The improved, accurate method of treatment of an eye's fundus according to claim 44, wherein in real time said position of said treatment zone is calculated from a point that is positioned selected from the group of locations consisting of a retina and a cornea and not including the treatment zone itself.

46. The improved, accurate method of treatment of an eye's fundus according to claim 29, further comprising the step of:

g. varying power of said treatment beam generated by said primary light source, to compensate for optical losses occurring along said optical path, in order to keep constant power on said retina.