WO1999058047A1 - Scanning laser ophthalmoscope for microphotocoagulation with minimal optical aberrations - Google Patents

Scanning laser ophthalmoscope for microphotocoagulation with minimal optical aberrations

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Publication number
WO1999058047A1
WO1999058047A1 PCT/US1999/009911 US9909911W WO1999058047A1 WO 1999058047 A1 WO1999058047 A1 WO 1999058047A1 US 9909911 W US9909911 W US 9909911W WO 1999058047 A1 WO1999058047 A1 WO 1999058047A1
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Prior art keywords
laser
beam
means
laser beam
ophthalmoscope
Prior art date
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PCT/US1999/009911
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French (fr)
Inventor
De Velde Frans J. Van
Original Assignee
Velde Frans J Van De
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/1025Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for confocal scanning
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F9/00821Methods or devices for eye surgery using laser for coagulation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00681Aspects not otherwise provided for
    • A61B2017/00694Aspects not otherwise provided for with means correcting for movement of or for synchronisation with the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F2009/00844Feedback systems
    • A61F2009/00846Eyetracking
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F2009/00861Methods or devices for eye surgery using laser adapted for treatment at a particular location
    • A61F2009/00863Retina
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/008Methods or devices for eye surgery using laser
    • A61F2009/00878Planning
    • A61F2009/0088Planning based on wavefront

Abstract

A combination of a confocal scanning laser ophthalmoscope and external laser sources (52, 54) is used for microphotocoagulation of the retina or the measurement of wavefront aberrations of the eye optics. An opto-mechanical linkage device (100) with beamsplitter (56) allows independent positioning of the pivot point (16) of the lasers of a scanning laser ophthalmoscope and the pivot point of non-scanning external laser beams. A similar pivot point location is used to minimize wavefront aberrations and to enable precise focusing of a therapeutic laser beam (52) on the retina. The pivot point of an external diagnostic laser beam (54) is systematically moved across the anatomical pupil when wavefront aberrations are to be measured. One confocal detection pathway of the scanning laser ophthalmoscope is used to localize fiducial landmarks on the retina. A second synchronized detection pathway is used to characterize the spot on the retina that is produced by the external laser beam. External laser beams (52, 54) can be polarized to eliminate specular reflections, and pulsed in anti-aliased fashion with its own confocal detection.

Description

SCANNING LASER OPHTHALMOSCOPE FOR MICROPHOTOCOAGULATION WITH MINIMAL

OPTICAL ABERRATIONS

Cross Reference to Related Applications

This PCT application is related to a previous PCT application Ser. N= PCT/US/97/21 53 , filed November 20, 1997, entitled "Scanning laser ophthalmoscope optimized for retinal microphotocoagulation, international publication number WO 98/22016, and the corresponding US application Ser. Ns 08/755, 48 filed November 22, 1996, now in allowance and entitled "Scanning laser ophthalmoscope optimized for retinal microphotocoagulation" The current PCT application is based on (1) the United States patent application Ser. Ng 09/075239, filed May 9, 1998, entitled "Scanning laser ophthalmoscope for retinal microphotocoagulation and measurement of wavefront aberrations, now in allowance, and (2) The US patent N2 5,892,569, issued April 6, 1999, filed July 18 1999, entitled "Scanning laser ophthalmoscope optimized for retinal microphotocoagulation"

Background - Field of Invention

The invention relates generally to instruments for examining and treating the eye and specifically to a scanning laser ophthalmoscope equipped with external laser sources for the purpose of retinal microphotocoagulation under the condition of minimal wavefront aberrations of the eye optics.

Background - Description of Prior Art

The ophthalmoscope is well known as an important device for examining the eye, and in particular the retina As a result of great interest in preserving eyesight, ophthalmoscopes of various constructions have been built The latest version of the ophthalmoscope, a scanning laser ophthalmoscope, is particularly appealing because of 2 its unique capability of combining infra-red and angiographic imaging of the retina with psychophysical procedures such as the study of visual fixation characteristics, visual acuity measurements and micropeπmetry A precise correlation between retinal anatomy and retinal functioning can be established with the scanning laser ophthalmoscope This retinal function mapping is now known to be very helpful to the surgeon when applying therapeutic laser Until now however, these therapeutic laser applications have been delivered to the retina with an instrument other than the scanning laser ophthalmoscope The use of different instruments renders the comparison of images the interpretation of psychophysical testing and precision of treatment more difficult

U S patent N° 4,213,678, issued September 29 1980 to Pomerantzeff et al, discloses a co-pupillary scanning laser ophthalmoscope for the purpose of diagnosing and treating retinal disease using two different intensity levels of the scanning laser beam One intensity range can be used for monochromatic imaging and angiography while a much higher level of the same laser beam or a different coaxial scanning laser beam is used for retinal photocoagulation Th s novel approach however is not ideal because of the technical difficulties in implementing safety controls for such a scanning therapeutic laser beam the difficulty in modulating the scanning laser beam over a range from non-coagulatmg to coagulating energies at video bandwidth and the non-thermal complications of high intensity pulsed laser beams m the nanosecond domain with an inappropriate duty cycle Pulsed thermal microphotocoagulation, as proposed before, is useful to restrict the impact of therapeutic applications to selective layers of the retina the retinal pigment epithelium or photoreceptors However, an appropriate duty cycle is necessary

Another solution that may be considered for effective thermal coagulation whether pulsed or continuous m nature, is to combine the scanning laser ophthalmoscope with a traditional external non-scanning therapeutic laser source However, it is impossible to image the spot of such therapeutic laser source on the retina with a traditional co-pupillary scanning laser ophthalmoscope

In the prior art, ophthalmoscopes, exemplified by the biomicroscope are optically combined with a non-scanning therapeutic laser source for the purpose of retinal photocoagulation Often, a contact glass is placed on the cornea to be able to view the retina with the instrument and a mirror is used for reflecting the therapeutic laser beam onto the desired retinal location through a small part of the pupillary area Importantly, the retina is illuminated and observed through different parts of the pupillary area to avoid reflexes l e Gullstrand's principle of ophthalmoscopy This optical arrangement makes the art of precise focusing of a therapeutic laser beam m the retina more difficult This is certainly the case in the presence of wavefront 3 aberrations, small pupil diameter or large diameter entrance beam of the treating laser.

Small therapeutic applications are often desired because they save retinal tissue, also they can be tailored to the shape of the lesion and they can take a variability in absorption more easily into account. However, photocoagulating ophthalmoscopes have been limited when consistent small or localized laser applications in the retina are desired because the anatomical changes caused by the therapeutic laser are often very difficult to visualize during treatment in the presence of photocoagulating light. This is even more the case if minimal intensity, i.e. threshold applications are desired. The critical endpoint of the laser application is often exceeded. The surgeon, upon recognizing the minimal anatomical changes on the retina, is also handicapped by a substantial human reaction time delay before he can interrupt the therapeutic laser. During this delay the laser continues to deliver energy to the retina and changes in the subject's fixation may occur. Since the reaction time of the surgeon may exceed 200 ms , a 100 s laser application can be delivered to the wrong place on the retina in the case of misalignment.

Also, it is difficult to permanently document previous laser applications on the retinal image because threshold applications themselves are usually not visible some time after the initial treatment.

Object, summary and advantages of the invention

The object of this invention is to combine in one instrument the capabilities of advanced imaging and precise psychophysics with microphotocoagulation of retinal tissue under conditions of minimal wavefront aberrations and documentation of small therapeutic laser applications for later reference. This is basically accomplished by selecting an entrance location of the external therapeutic laser beam that is subject to minimal wavefront aberrations, through observation of the retina with the scanning laser ophthalmoscope using the same entrance location for the scanning lasers. As documented in the prior art, Gullstrand's principle is used differently in scanning laser ophthalmoεcopy, hence the necessity to use a similar optical pathway for both the external therapeutic or diagnostic and scanning laser beams. Seven features of the invention are :

(1) A special coupling system between a confocal scanning laser ophthalmoscope and external laser sources. This comprises an optimally coated beamsplitter and optomechanical linkage device. The linkage device allows the spatial matching of the pivot point for the fast scanning diagnostic laser beams of the scanning laser ophthalmoscope with the pivot point of the non-scanning external therapeutic or diagnostic laser beams. Optimizing the Maxwellian viewing of a retinal location will 4 then also result in a minimal wavefront aberration for the external laser beams because the same pivot point is used. Also in this situation, the amount of prefocusing necessary to image with the scanning laser ophthalmoscope on a specific retinal layer is a reference, if needed, for focusing the therapeutic laser beam with its proper telescopic optics.

(2) As mentioned before, a non-confocal or co-pupillary scanning laser ophthalmoscope cannot be used to image the external laser spot on the retina. The confocal instrument can do this, however not in a straightforward manner. It is important to realize that the image of the external laser spot on the monitor, is actually a convolved image of the external laser spot with the confocal aperture. Often, the confocal aperture of the scanning laser ophthalmoscope is larger and hence the backscatter image cannot be used directly to determine size or adjust focusing. The foregoing necessitates either an indirect verification of focusing by using the same pivot point for imaging and relying on the focusing of the retinal image, or as an alternative, the use of a combination of two apertures with different size pinholeε and transmission characteristics .

(3) Although it is possible to realize part of the invention with one detector pathway, considerable advantages are derived from using two detectors that are temporally synchronized in the confocal scanning laser ophthalmoscope. Reasons for example, are the weak contrast of the aiming beam on the retinal image, obscuring therapeutic light, and the fact that the retina and therapeutic laser spot can move independently of each other. Using an appropriate beamsplitter and filters, one detector images the retina, its pigment distribution and the anatomical changes caused by the therapeutic laser, unimpeded by the external laser light. Reference fiducial landmarks in the retinal image can be retrieved with two-dimensional normalized grayscale correlation faster than human reaction time would allow. A second synchronized detector images only the backscattered light from the external laser beams, without a background of moving retinal details. This image can be localized using simple image processing techniques such as look-up table manipulation. The implementation of a two detector pathway therefore allows registration of external laser beams referenced on the retinal image, and the use of a safety shutter in case of excessive misalignment. It should be noted that this specific part of the invention could equally well be applied to traditional photocoagulating systems if they are equipped with two video cameras, as long as the detector images are made spatially congruent .

(4) An aiming or diagnostic beam of different wavelength than the actual therapeutic laser source is typically polarized. Its light is partially transmitted after backscattering from the retina, through the beamsplitter. Only the aiming or diagnostic beam wavelength is reaching one of the photodetectors . Polarization removes 5 the strong corneal reflections that may appear as a second confusing spot or veiling on the retinal image

(5) Pulsing of the aiming or diagnostic beam allows higher but still safe peak power to be used Pulsing of the aiming beam requires anti-aliasing relative to its confocal detection on the retina

(6) If a diagnostic external laser source is used, the same opto-mechanical linkage device can also determine the wavefront aberrations of the complete eye optics by systematically varying the entrance location of the external laser beam in the plane of the anatomical pupil The differences in retinal location of the diagnostic laser beam for each entrance location are measured imaged, or neutralized with small angulat ons of the external diagnostic laser beam It is well known m the prior art how to reconstruct the wavefront aberrations over the pupil from individual slope measurements (Zernike) Precise knowledge of the higher orders of the wavefront aberrations is then useful to correct the shape of a wide entrance Gaussian external laser source thereby permitting even more localized thermal applications

A major advantage of the invention is the ability to accurately deliver and document small, minimal intensity therapeutic laser applications to selected layers in the retina subject to minimal wavefront aberrations hence the term microphotocoagulation With the proper combination of wavelengths, beam and pulse characteristics, selective targeting of the photoreceptor layer or retinal pigment epithelium layer can be accomplished Immediate micropeπmetric and angiographic feedback is available Microphotocoagulation has the ability to remove temporarily or permanently a percentage of the metabolically very active photoreceptors or retinal pigment epithelium cells, while minimizing damage to other anatomical structures, especially the choriocapillary layer, Bruch s membrane, ganglion cell layer and neural tissue in between applications Virtual oxygen windows , reducing relative hypoxia, can for example oe established through reduction of the demanding metabolic load of the central retina This approach is useful in the retardation of onset or prevention of drusen related and neovascular age-related maculopathy Possible mechanisms are an accelerated removal of material that thickens Bruch' s membrane and the reduced production of angiogenetic factors caused by relative hypoxia Debridement of retinal pigment epithelial cells may lead to the removal of infectious agents, accumulated mtracellular material or replacement of otherwise defective retinal pigment cells The retinal location, focusing, size, intensity and duration of often invisible therapeutic laser applications can be stored and used for follow-up evaluation Further objects and advantages of the invention will become apparent from a consideration of the drawings and ensuing description of preferred embodiments 6

Description of the Drawings

Fig 1 is a diagrammatic representation, illustrating the different components of the confocal scanning laser ophthalmoscope optimized for microphotocoagulation Three subparts can be distinguished (1) A confocal scanning laser ophthalmoscope with lasers of visible and infra-red wavelengths, synchronized detectors, beamsplitter, confocal apertures with different filters, collimator-telescope prefocusmg optics, scanning optics, sync and video-generating electronics, acousto-optic (AOM) or direct electrical amplitude modulation (EAM) of lasers (2) External therapeutic or diagnostic non-scanning lasers with modulation options, coupled to the scanning laser ophthalmoscope with the help of a beamsplitter and opto-mechanical linkage device, safety shutter, collimator-telescope, and interface electronics (3) The computer with one or more linked overlay framegrabber graphic cards, capable of digital image processing, and monitor

Fig 2 details the opto-mechanical linkage device coupling external laser sources and confocal scanning laser ophthalmoscope Angulation of the laser beam is possible mechanically or with the help of motors under CPU control The pivot points of external lasers and scanning lasers can be adjusted relative to each other Overview image and different components of one embodiment are given Reduced embodiments only permit parallel positioning of a diagnostic laser beam

Fig 3 details the ray tracing of the scanning laser ophthalmoscope and external therapeutic or diagnostic laserbeams In Fig 3a, a common pivot point s used to avoid lens changes, thereby resulting in minimal wavefront aberrations and predictable focusing of the laser beam in the retina Wavefront aberrations cause a difference in slope of refraction In Fig 3b, spurious reflections are demonstrated at the anterior corneal interface They are minimized by polarization techniques and optical stops

Fig 4 shows a block diagram of an overlay frame grabber card capable of advanced image processing The one or more overlay frame grabber graphic cards have an input interface frame memory, display interface and CPU interface Besides the OFG cards the host bus accommodates a I/O for interaction with several components of the therapeutic laser assembly and opto-mechanical linkage device Essential electronic pathways include (1) Synchronized video-m pathway from SLO detectors (2) Video-out pathway to monitor and laser modulators (3) System timing generator with genlockmg of the other components including A/D converters and D/A converters of the different boards 7

Fig. 5 details the contents of part of frame memory of an OFG card with video coming from a first detector. A search window within the video retinal image contains a gray scale pattern that is used to determine the coordinates of fiducial landmarks of the retina with a normalized gray-scale correlation algorithm.

Fig. 6 details the contents of part of frame memory of an OFG card with video coming from a second synchronized detector. The coordinates of the location of the external beams can be determined with simple digital image processing techniques and indicated on the retinal image with the help of overlay graphics.

Fig. 7 is a schematic that illustrates the importance of a minimal fiber optic aperture and low N.A. to match the f/# of the receiving optics, i.e. the eye. Entrance pupil is limited to 2 mm. Back focal length of the eye is assumed to be 22.28 mm.

Fig. 8 illustrates a stationary raytracing of the scanning lasers through the eye. Gaussian beam optics. The 1.0 mm beam focuses to a small spot of about 25 μ in the retina. Not to scale. The different retinal layers, virtual retinal conjugate aperture of about 100 μ and backscattered rays from a non-scanning external laser source are indicated. The 75 μ backscatter predominantly originates from the internal limiting membrane and pigment epithelium.

Fig. 9 is a schematic that illustrates a double wheel with confocal apertures for the external laser beam and scanning laser beams respectively. The thin confocal apertures for use with the external laser beam are smaller than those for use with the scanning laser beams and they are constructed of a thin material that passes the scanning laser beam wavelength used for imaging the retina. Separation of confocal apertures can neutralize the small longitudinal chromatic aberration of the system.

Fig. 10 illustrates a video image used for modulating a Gaussian therapeutic laser source with an AOM or EAM. Example pulse characteristics are 100 % pass during 50 pixels or 5 μs, every 1 ms or approximately 15 video lines. Aliasing, especially of the aiming or diagnostic beam, can be eliminated with an additional stimulus graphic in the appropriate location.

Reference Numerals in Drawings

10 Gaussian beams of laser light of scanning laser ophthalmoscope, coaxial

12 Posterior pole of the eye, retina

14 Scanning optics, including polygon and galvanometer, additional lenses, mirrors 8 Similar Maxwellian view of scanning and therapeutic beams, common pivot point Collimator-telescope for scanning laser beams of ophthalmoscope Lens changes scattering elements in the optical media of the eye Backscattered light returning from the retina Beamsplitter or aperture for separation of incident and backscattered laser light Combining beamsplitter (polarizing) Avalanche photodiode detectors Video and sync generating electronics of scanning laser ophthalmoscope Computer Overlay frame grabber graphic cards Video display monitor SLO diode infra-red 792 nm laser for imaging purposes SLO He-Ne 633 nm laser for microperimetπc purposes Pair of adjustable linear polarizers, attenuators Acousto-optic modulator Overlay on retinal image indicating characteristics of external laser spot Barrier, interference or polarizing filters, optionally with pinhole in 200 or 202 Beamsplitter for separating scanning (imaging) and external (aiming) laser beams External, non-scanning therapeutic laser , e g frequency doubled diode pumped YAG Second wavelength external laser source, e.g diode 635 nm or 670 nm Beamsplitter combining light from scanning and external laser sources Opto-mechanical linkage device Collimator-telescope for external laser beams Safety shutter acousto-optic modulator, or mechanical chopper Electronic circuitry for elements 52, 54, 58, 60, 62 I/O link between supporting electronics 64 and computer

Joystick-micromanipulator

Reflected light at the anterior corneal interface

Adjustable mirror hinges, interconnected with ball-bearing adjustable cylinders Support arc for positioning distal element 100 Pair of support arcs for positioning element 102 Supporting framework for elements 100, 102 and 104 Adjustable leadscrew support for positioning element 106 Framework with adjustable lead screw to position element 108 Motors screws or mechanics to position the elements 100 104, 106, 108 Fixed attachment to the scanning laser ophthalmoscope of element 58 116 Ball-bearing cylinders with rotational and translational capabilities 118 One half of clamp around torical support arc 120 Torical support arc, completely closed

150 Dioptric media of the eye, eye optics

152 Cornea

154 Lens of the human eye

156 Anterior chamber fluid

158 Vitreu

160 Complete retina

162 Photoreceptor layer

164 Nerve fiber layer with internal limiting membrane

166 Choriocapillary layer

168 Retinal pigment epithelium layer

170 Bruch s membrane layer

172 A virtual conjugate image of apertures 200 and 202, if adjusted to coincide

174 Scattering from non-scanning external laser source at the retina

176 Raytracmg of stationary scanning laser (Gaussian) through optic media

200 Wheel containing different apertures for external laser sources

202 Wheel containing different confocal apertures for scanning laser sources

204 Small opening tightly confocal thin aperture, transparent for scanning lasers

206 Larger opening less confocal aperture for scanning laser sources

208 Similar to 204

210 Larger confocal opening when compared with 206

250 Pixels representing high intensity interval of modulated therapeutic laser

260 Videolmes representing interval between therapeutic laser pulses

270 H gh intensity pixels drawn into video image to counter aliasing of aiming beam

300 Fiber carrying 532 nm laser light from source 52

302 Aperture of 75 to 100 μ, numerical aperture N A 0 05-0 08

304 Combining beamsplitter

306 Polarizer

308 Acousto-optic modulator

310 670 diode laser source, aiming beam 54

312 Relay optics, inclusive element 60 and optional field lenses

314 Receiving optics eye with f' 22 28 mm and having f/10, 2 mm entrance pupil

316 Fiber optic similar to element 300 1 0

Detailed Description and Operation of an Embodiment

A representative embodiment of the confocal scanning laser ophthalmoscope for retinal microphotocoagulation is illustrated in Fig 1 The principles of scanning laser ophthalmoscopy are described in detail in the prior art (Pomerantzeff, Saban, Webb Plesch) Features of the confocal scanning laser ophthalmoscope that are relevant to the invention are further discussed

I THE CONFOCAL SCANNING LASER OPHTHALMOSCOPE

A prefocused Gaussian beam of laser light 10, e g consisting of a combined polarized He-Ne 633 nm and diode 792 nm wavelength, and having an approximate diameter of 1 0 mm at the entrance of the eye, is further focused by the eye optics of approximately 60 units of dioptric power to a spot m the retina This spot typically between 10 and 30 μ in diameter at a retinal plane is scanned over the posterior pole of the eye 12 in a sawtooth manner with the help of scanning optics, currently comprising a polygon and galvanometer driven mirror 14 Fast horizontal 15 KHz and slower vertical 60 Hz deflections of this flying laser spot are synchronized to a standard video RΞ-170 signal They create the rectangular laser beam raster on the retina A rectangular area of about 0 5 en on the retina is illuminated in the 40 degree field of view of the instrument A Maxwellian view illumination is used m the scanning laser ophthalmoscope The pivot point 16 of the scanning laser beam is well-defined and is usually positioned m the plane defined by the anatomical pupil The amount of prefocusmg of the laser beam is adjusted with a collimator-telescope 18 This telescope is capable of positioning the waist of the Gaussian beam at specific planes in the retina The field of view can be changed from 40 degrees to 20 degrees with the help of additional mirrors In the 20 degree field of view, the pivot point 16 of the Maxwellian view is wider in diameter as the Gaussian beam diameter is also doubled Because of the wider beam in the 20 degree field of view, it will be more difficult to minimize wavefront aberrations by moving the pivot point around focal scattering or absorbing elements in the ocular media 20 Also, the focusing range will be reduced four-fold this in accordance with Gaussian beam optics

In the confocal scanning laser ophthalmoscope, the light that is backscattered and reflected from the retina 22 now distributed in the anatomical pupil is descanned over the same optics and separated from the illuminating beam at a mirror-pmhole 24 This mirror-pmhole 24 is optimally positioned with regard to light collection, e g close to a pupillary conjugate plane and the pinhole also blocks most of the perpendicularly and specularly reflected light coming from the anterior surface of the cornea along the same path that was used for the illumination Other options are 1 1 available and have been used before For example, a polarizing beamsplitter can be applied in combination with a polarizing filter Th s would allow the use of axially backscattered light from the retina with some advantages, but puts other optical constraints, especially with regard to polarization and intensity on the illuminating sources The returning light is focused to pass through a small aperture 200, 202 This aperture, for example having a diameter of 1 mm, is conjugate with a virtual aperture 172 of typically 100 μ at the retinal beam waist Therefore, it moves along with the illuminating beam of the SLO It is used to reduce the impact of the multiple backscattered light outside the illuminated area on the retina As a result contrast of the image is considerably enhanced A smaller aperture would reduce the amount of light returning to the detectors and render the images more confocal Not to cut back too much on the returning light, especially m the presence of a pinhole 24, the aperture is sometimes up to three times larger than the actual retinal spot being illuminated The amount of light that falls on an avalanche photodetector 28 after passing appropriate filters is translated into an analog signal by the video and synchronization generating circuitry 30 of the scanning laser ophthalmoscope This signal is synchronized to the master timing provided by the rotating polygon The video signal is then relayed to the overlay frame grabber graphics cards 32 within the computer 34, which in turn will display the processed signal onto a display monitor 36 with appropriate overlays 46

Often two laser sources are combined to illuminate the retina The two lasers serve a different purpose For example, a high intensity diode infra-red 792 nm laser 38, under electrical modulation control and vertically polarized, is nearly invisible to the observer It produces the retinal image on the display monitor 36 An aligned and low intensity He-Ne 632 8 nm laser 40, horizontally polarized is modulated with a pair of linear polarizers 42 and acousto-optic modulator 44 The 633 nm laser 40 is used to draw visible graphics in the laser raster These visible graphics are created by amplitude modulation of the laser 40 For this purpose, the acousto-optic modulator 44 is usually driven by the same computer overlay frame grabber graphics card 32 The graphics which are seen by the observer, are usually not visible m the retinal image, unless when they are very bright The exact position and characteristics of the graphics can however be indicated in real-time on the retinal image with the help of computer generated overlays 46, because the image video that comes out of the scanning laser ophthalmoscope and graphics video that modulates the acousto-optic modulator 44 are synchronized to the same timing signals provided by the synchronization generating circuitry 30 The 632 nm He-Ne laser 40, typically used for generating the graphical stimuli at lower intensities could however also be used for imaging at higher intensity levels 12

Multiple and synchronized detectors 28 and multiple laser sources 38,40 have been used before in the original red-yellow krypton color co-pupillary scanning laser ophthalmoscope. Appropriate barrier filters, interference filters 48, and separating beamsplitter 50 are necessary in this situation, matching the different wavelengths that are used. Barrier filter properties can also be combined with apertures 200, 202. Some field lenses and additional optical elements to switch between the 20 and 40 degree field of view have been omitted from the schematic.

Surface-emitting quantum-well laser diodes are of increasing interest, and offer the advantages of high packing densities on a wafer scale. An array of up to a million tiny individually modulated cylindrical In0.2Gao 8^s surface-emitting quantum-well laser diodes, VCLES, with lasing wavelengths in the vicinity of 970 nm and shorter can substitute the traditional laser sources 38, 40 and scanners 14 if coupled with a two-dimensional detection array. The use of such a specific extended detection array has been discussed in the original U.S. patent 4,213,678.

II . DIFFERENT EXTERNAL LASER SOURCES AND THEIR CONTROLLING MEANS

External therapeutic laser sources 52, 54 are well known in the prior art, e.g. argon 488 nm, 514 nm or currently diode laser 52, having the possibility of emitting different wavelengths, for example 532 nm, 810 nm and 1064 nm. A variable part of the optical transmission usually occurs in fiber optics. The advantage of fiber optics is flexibility and a more even intensity profile at the exit aperture of a multimode fiber. Multimode propagation of higher intensity laser beams and fiber optics transmission are more difficult to focus to a small spot size when compared with a fundamental mode Gaussian beam due to the M2-factor of propagation or limitations in N.A. of the optical fiber. A pure Gaussian profile of the external laser would be used for the purpose of measuring wavefront aberrations of the eye or very small therapeutic applications, as is briefly explained in the following section. The external therapeutic lasers can be pulsed, for example with the help of an acousto-optic modulator 62 or Pockel cell. Either first diffracted or undiffracted zero order beam can be used. If different wavelenghts pass through the AOM, achromatizing prisms can be used. It is also possible to use an attenuated and zero order as aiming beam, after optical recombination with the modulated first order beam. It is difficult to modulate a multimode laser beam of 50 mrad divergence. A large Bragg angle and therefore high frequency carrier signal e.g. of 1 Ghz would be necessary. A Gaussian profile 300 mW output at 532 nm (Crystalaser, Irvine CA) however is easy to modulate with the AOM. The light can be then fed into a special optical fiber for mode scrambling. A mechanical light chopper 62, can also be inserted in the optical path of the therapeutic laser beam. An example is a circular disc of 150 mm 13 diameter pierced with 0.5 mm holes at the outer edge. A motor with rotation speed of up to 5000 RPM can be used. Several pulse characteristics can be created with adjacent trajectories on the wheel. The wheel can then be moved to select one. Direct electrical modulation using video for the aiming beam diode laser and diode pumped doubled frequency laser 52 or Q-switchmg of a continuously pumped Nd-YAG laser are other options The modulation characteristics are further discussed This pulsing is done to selectively target absorbing layers, for example the pigment epithelium 168 Therapeutic lasers can be used in association with absorbing dyes In photodynamic therapy a photosensitizing drug is first injected and laser of appropriate wavelength is then applied w th the aim of closing off small bloodvessels In a second stage, conventional 514 or 532 nm photocoagulation can penetrate more completely in deeper layers because the blood flow has been halted before with the photodynamic therapy Hemoglobin molecules that are fixed are far more effective in absorbing energy, together with the melanin pigment In photodynamic therapy, an aiming beam and therapeutic beam of e.g 664 nm or 695 nm can be the same Typically, the therapeutic beam is left on for 120 seconds or longer, and larger areas on the retina are illuminated

A large Gaussian beam diameter 1064 nm source 52 could also selectively coagulate layers in the retina, e.g. photoreceptors, with proper focusing The main absorbant element will be water as 50 percent of the incident 1064 nm light will reach the retina. Water is ubiquitous, hence the danger of damaging the innermost retina or deeper layers Therapeutic wavelengths e.g. 532 nm and 1064 nm, could be combined m variable proportion to enhance the coagulation of a specific layer such as the photoreceptor layer In order to be able to use the large Gaussian beam diameter for focusing purposes, wavefront aberrations have to be minimized as further explained Often, a low power diagnostic beam 54 of different wavelength, typically a diode laser m the 630-700 nm range, is provided for aiming purposes. It can be merged at different places with the high power beam 52, pulsed, and it can also be polarized as energy reduction is of less concern for the aiming beam Polarization has significance m eliminating spurious reflexes from the cornea as further explained Alternatively, the high power therapeutic laser beam 52 could also serve as an aiming » beam at much lower intensities, but would be required to continuously emit power Other elements in tne optical construction of the therapeutic laser include a safety shutter, aperture stops at the end of the fiber optic, various filters and the modulating devices 62 allowing specific pulsating patterns of energy, typically in the μs domain. The foregoing components are controlled by electronic circuitry 64 known in the prior art. In addition, an I/O link 66, often a combination of TTL circuits exists between the control electronic circuitry 64 of the external lasers and the computer 34 This electronic connection 66 can signal to the computer 34 14 when the external lasers 52 and 54 are used and also allows activating the modulating means 62 under control of the computer 34

As an example we will further elaborate specifically on the 532 nm doubled Nd-YAG laser In the current embodiment, an external 670 nm diode s used as aiming laser 54. This diode can be electrically or AOM modulated using computer 32 and anti- aliased with each update of the retinal image. The aiming beam has to be on only when the confocal aperture of the SLO is m its neighborhood. For this purpose, the aiming beam location is already approximately known by the computer because it knows the coordinates of the joystick-manipulator and the previous location of the aiming beam Higher peak powers can then be safely used if necessary

External diagnostic and non-scanning laser sources 52, 54 include He-Ne red, He-Ne green, and optimized, collimated mono-modal fiber diodes They are used for the reconstruction of wavefront aberrations across the anatomical pupil of the eye Clean and small diameter beam profiles are important. They produce a relatively small spot on the retina with a large depth of focus External diagnostic lasers 52, 54 differ from the therapeutic sources in the maximum power output they can produce Surface- emitting quantum-well laser diodes are of increasing interest, and offer the advantages of high packing densities on a wafer scale. An array of individually modulated cylindrical In0 2 Gao 8 As surface-emitting quantum-well laser diodes, VCLES, with lasmg wavelengths in the vicinity of 970 nm and shorter can substitute the external diagnostic laser sources 52, 54 and their translational movement as described n a later section A collimator-telescope e g made of a selfoc planar microlens array material, adjusts the spacing and alignment of about 60 individual laser beams from the VCLES which is computer activated.

Ill OPTO-MECHANICAL LINKAGE OF SLO AND EXTERNAL LASERS

The external therapeutic laser beams 52, 54 are non-scanning, however their orientations are allowed to change using a special transmission system comprising an appropriately coated beamsplitter 56 and opto-mechanical linkage device 58. Fig. 2 illustrates the essential components of the opto-mechanical linkage device 58 between the external therapeutic laser sources 52, 54 and the confocal scanning laser ophthalmoscope for the purpose of microphotocoagulation Also, the methods are described by which (1) the position and characteristics of the external laser beams 52, 54 are referenced on the retinal image, (2) a precise focusing is obtained for the purpose of microphotocoagulation, and (3) wavefront aberrations influencing the shape of the therapeutic laser beams are minimized Also (4) the optical constraints are discussed with regard to optical throughput, as are (5) the characteristics of the different possible Darner, bandpass interference and polarizing beamsplitters. (6) 15

Also it is necessary to reduce the specular reflections from the anterior surface of the cornea

A part of the opto-mechanical linkage device 58 that transmits the therapeutic laserbeams is often realized with a combination of extendable mirror hinges 100 Enough degrees of freedom are available with the mirror hinges 100 as to permit an unimpeded movement of the laserbeams m a rotational and translational fashion The hinges themselves are connected with ball bearing elements 114 for smooth rotation and extension

In one embodiment the opto-mechanical linkage device 58 consist further of a framework or base 106 that permits a support arc 102 to slide across using another pair of support arcs 104 The support arcs are part of a toroid 118 and can contain a groof or thread The last mirror hinge 100 can contain additional optical elements and is attached to the support arc 102 The proximal or first mirror hinge 100 is fixed to the SLO The terminal part of the transmission optics can slide along the support arc 102 w th the help of an attachment 116 and reflects the therapeutic laser light 52 54 coming from the other components in the opto-mechanical linkage device 58 towards the posterior pole of the eye 12 The two sliding movements allow the external laser beams 52 54 to move perpendicular to a curved surface e g a part of a sphere such that the external laser beams 52 54 will have a pivot point 16 that is very similar in location to the pivot point of the Maxwellian view of the scanning laser ophthalmoscope The two sliding movements can be produced with the help of stepper motors 112 but several other means and methods can be easily envisaged to perform this function either manually or motorized A micromanipulator-joystick 78 s used to control these stepper motors or mechanical movements The joy-stick 78 is moved by the surgeon to select a retinal location to treat The supporting framework 106 typically measures about 100 mm by 100 mm and is attached to the confocal scanning laser ophthalmoscope through the adjustable supporting elements with optional leadscrews 108 and 110 The elements 108 and 110 permit the framework 106 to move translationally in two directions They allow calibration so that the two pivot points coincide

The prefocused external laser beam 52 usually has a 0 5 mm to 2 mm diameter at the entrance position m the eye depending on the desired spot size on the retina the diameter of the fiber optic and its numerical aperture The external beams 52, 54 are prefocused by a collimator-telescope 60 using as a reference the amount of prefocusing of the scanning laser beams 38, 40 for the same retinal location and using the same pivot point 16

Essential m the optical pathway is a collimator-telescope 60 and optional field lenses for precisely selecting the spot size and focusing of the external laser beams 52 54 in a specific retinal plane The amount of focusing that is needed for the 16 external laser beams 52 and 54, is related to the amount of prefocusmg of the scanning lasers 38 and 40 for the same retinal area since the same optical pathway s used through the ocular media This focusing can further take into account the dispersion of light that is caused by differences in wavelength Longitudional chromatic aberration is more important than lateral chromatic aberration because of the fact that the angular displacements in the eye measured from normal incidence are usually small for our purposes The longitudinal differences have been tabulated before and amount e g to approximately 0 75 D for 532 nm and 792 nm, approximately 0 5 D for the difference between 670 nm and 792 nm It is possible to use biometπc data derived from the keratometer and biometπc ultrasound to further refine the raytracmg in the eye A real time computer algorithm can actually plot, using the foregoing data, on the computer screen the approximate raytracmg inside the eye This is useful since the surgeon will then be able to see that the minimal waist or focus of the beam is situated anteriorly or posteriorly of the retina The collimator- telescope 60 can be manually or automatically adjusted according to the reading of the SLO and this can be done on a continuous basis or with fixed interval settings If the radius of the gimbaled part of the optomechanical linkage device 58 can be made large enough the focusing elements can be built nto the last element 100 and directly coupled to the end of the fiber optic This simplifies the construction since no additional extendable mirror hinges are necessary in this case

It is important to understand the raytracmg of scanning and external laser beams for the purpose of minimizing specular reflections from the anterior surface of the cornea and of wavefront aberrations in the optical media An optional lens, positioned on or near the anterior surface of the cornea, can be useful to reduce wavefront aberrations of the anterior surface Its refraction characteristics may be derived from the knowledge of the wavefront aberrations as described before Fig 3a illustrates the different possibilities that can exist an eye having some lens changes or scattering elements 20 in the dioptric media that cause wavefront aberrations Such changes however can occur at the cornea or in the vitreous as well In order to ensure that both the scanning lasers 38, 40 and external lasers 52, 54 are subject to similar wavefront aberrations it is necessary that these beams use the same path and hence the same pivot point 16 This pivot point 16 can be chosen by the observer so that a particular retinal location is seen in good focus with minimal aberrations on the monitor 36 As a result, the therapeutic external laser beams 52, 54 will also undergo minimal aberrations and will be easily focusable using the telescope- collimator 60 Also vignetting is avoided and smaller entrance pupils can be used when compared with slitlamp based coagulators If the pivot points 16 were different aberrations could influence both the beamshapmg and focusing of the therapeutic laser spot This phenomenon is actually exploited to reconstruct the wavefront aberrations 17 of the eye In the presence of aberrations, a diagnostic external laser spot on the retina will be different by a various amount m quality and more important m location for the different parallel entrance positions into the eye optics Some of the different retinal locations are illustrated m Fig 3a These differences m location relative to a reference spot created by a fixation target m the scanning laser ophthalmoscope can be recorded by the frame grabber and subsequently analyzed great detail Alternatively, the subject could slightly alter the orientation of the external diagnostic beam 52, 54 or even fixation target as to neutralize the difference in location on the retina The amount of angulation, I e slope, that is required is again a measure of the degree of wavefront aberration corresponding to a particular entrance position of the external beam into the eye optics The data coming from a grid of different entrance positions is used to reconstruct the wavefront aberrations across the anatomical pupil of the eye using e g the well-known method of Zermke polynomial analysis or equivalent algorithms

In Fig 3b reflections at the anterior corneal surface are raytraced Usually, the angle between incidence and reflection is small As previously explained, strong direct perpendicular reflections 90 from the scanning lasers themselves are suppressed at the aperture 24, skewed angulated reflections 90 are mostly rejected because the confocal aperture 200, 202 is not looking at their virtual retinal location of origin This mechanism of suppression does however not hold for the therapeutic lasers 52, 54 since their reflection 90 w ll be registered by the moving confocal aperture 200, 202 The moving of the aperture vis a vis a stationary therapeutic laser spot is illustrated in Fig 8 and further explained below This causes spurious reflections that can be confused with the real location of the therapeutic spot on the retina To solve this problem, the 670 nm aiming beam 54 is polarized The corneal interface index of refraction is approximately 1 33, therefore the intensity of reflection amounts to about 2% The angle of reflection is usually much smaller than the Brewster angle of 53 degrees In fact, up to 30 degrees of reflection angle, both s- and p-polaπzation components will be present If the aiming beam 54 is polarized th s orientation w ll be primarily returned to the detector 28 where it can be intercepted with an orthogonal polarizer 48 e g Melles-Griot # 03FPG001 An additional interference filter 48 e g Melles-Griot 03IFS014 can isolate 60 percent of the 670 nm light It blocks the high intensity and non-polarized 532 nm The optical media, e g nerve fibers, have a polarizing capacity that is incomplete hence the mechanism of suppression will work It is possible however to change the orientation of polarization according to the retinal location to maximize performance if necessary

Focusing optics are illustrated Fig 7 and Fig 8 In Fig 7 the aperture of a multimodal cladded fiber optic with diameter of 75 μ is in the object plane 18

Divergence of the mixed multimodal output beam of 532 nm is limited to a numerical aperture N.A. of about 0.05. A circular opening produces a clean edge and passes 90 % of the output power. This beam is then merged with the aiming beam of 670 nm, properly polarized and having the same divergence characteristics, e.g. by sending this light through the same type of optical fiber. Further focusing optics including field lenses and the collimator-telescope 60 have been discussed. If the smallest spot size of 75 μ on the retina is desired, then the magnification factor will be one and consequently the same N.A. or f/10 has to be used at the entrance pupil of the eye. The backfocal length of the eye being 22.28 mm results in an entrance pupil of about 2 mm, which is a reasonable limit. Larger spot sizes will then require a smaller entrance diameter. From the discussion above it is clear that a fiber with minimal N.A. i.e. divergence, smallest diameter and minimal power loss is advantageous. The mode mixing within the fiber creates a reasonable flat profile at the exit aperture, thus avoiding the peaked central power of a Gaussian beam.

Beamsplitters 50, 56 are specifically coated to reflect for the wavelength and polarization of the external lasers 52, 54, but are highly transparent for the wavelengths of the imaging scanning laser 38 of the scanning laser ophthalmoscope. Beamsplitter 03BTF011 from Melles-Griot reflects 70 % of the 532 nm light, transmits 95 % of the properly polarized 792 nm light, reflects 70 % of the s-component of 670 nm, transmits 40 % mixed polarization of 670 nm. An alternative beamsplitter, cold mirror Melles-Griot 03 MCS007 transmits 90% of 792 nm, reflects over 97 % of 532 nm, and reflects 20 % or transmits 80% of 670 nm light. The task of the beamsplitter 56 is to direct the external laser beams 52, 54 and various scanning laser beams 38, 40 of the scanning laser ophthalmoscope towards the posterior pole of the eye 12. Some external diagnostic laser light 52, 54 is however permitted to pass the beamsplitter 56 in order to reach a photodetector 28 after returning from the retina. The task of beamsplitter 50 is to direct the returning light from scanning lasers 38, 40 and external lasers 52, 54 to different detectors 28. E.g. Melles-Griot long wave pass filter 03 BDL001 separates the 532 and 670 nm from the 792 nm. The remaining transmitted therapeutic light 52, 54 after the beamsplitter 50 is absorbed by a filter 48 in front of one of the detectors, to avoid confusion with the descanned laser light 38 or 40 that is returning from the retina.

As mentioned before, both detectors 28 and circuitry 30 generate video that is genlocked to a common master timing signal derived from the spinning polygon. This property will be exploited in referencing the external laser beam location onto the retina. For this purpose one detector 28 is provided with a barrier filter 48 to eliminate all wavelengths of light returning from the retina except the external laser wavelength of 670 nm. Image processing is applied to determine the position of the light from the external laser beams in the video-signal. Because of the 19 synchronization of the video generated from the detectors 28 within the overlay frame grabber graphic card(s) memory 32, a precise indication of the position of the external laser beams 52, 54 is possible using overlays 46 on the retinal image produced by the second detector 28. The overlay can be pseudo-colored and semi- transparent to imitate the look and feel of an aiming beam on the retina using the regular optical slitlamp. It is important to realize that this separation of laser beams at the detectors 28 is desired for multiple reasons. First, it is easier to see the progression of retinal coagulation in the absence of the treating light. Second, the high power of the external laser beams makes their precise localization on the retina impossible because of oversaturation of the video. Third, tracking algorithms as explained below cannot work efficiently in the presence of a retina that can move independently in a different direction when compared with the position on the retina of the external laser beam that can move in another direction.

Fig. 5 and Fig. 6 summarize what is seen by the two synchronized detectors 28. In Fig. 5 only the scanning lasers 38, 40, and most often only the scanning IR laser 38 responsible for the retinal image, is contributing. The graphics however can be seen as overlays 46 as previously explained. Diverse retinal features can be used as fiducial landmarks, e.g. the branching pattern of vessels or pigmentary changes. In Fig. 6 only the external lasers 52, 54 will contribute to the image.

Conventional laser delivery systems can also be equipped with e.g. two monochrome CCD cameras that are attached to the slitlamp with the help of beamsplitters. One color CCD camera that registers the attenuated green light in one channel with the help of filters and the red fundus light on another channel can also be used. The spatial congruence is equivalent to the temporal alignment found in the SLO system. Overlay graphics can then be employed in a similar fashion and registration can also be performed.

Location, focusing, size, duration of application and intensity of the therapeutic laser beam can be stored, retrieved and used in other treatment sessions. It is also possible to plan laser applications at particular locations on forehand. Since the registration of the therapeutic laser beam location is happening in real-time, simultaneous retinal image registration using a technique outlined in the next chapter, will show whether the intended therapeutic laser beam location is still selected within the desired area on the retina. If the algorithm is fast enough realtime indication of the next location to be treated is possible. A map of treated locations is available to the surgeon. If a misalignment occurs, the TTL circuitry 66 will activate the shutter 62 and interrupt the therapeutic laser beam 52. This is very advantageous since such interruption is likely to occur much faster than human reaction would allow. 20

The external laser beams 52, 54 will generate a convolved image with the confocal aperture on the monitor 36 This can be understood by examining Fig 8 In this Fig 8, the scanning laser beam 176 is flying across the retina while transvers g the dioptric media of the eye 152, 156, 154, 158 Further visualized are the virtual confocal aperture 172 situated at the waist of the scanning laser beam 176, and the different parts of the retina, 164, 170, 162, 168, 166 An external laser beam 52, 54 produces the stationary retinal spot 174 This retinal spot backscatters light, e g from the retinal pigment epithelium 168 and internal limiting membrane If the confocal aperture is larger than the retinal spot then a blurred image of the opening of the confocal aperture 172 will be generated on the monitor 36 through convolution of the external laser spot 174 with the confocal aperture It is possible to enhance the resolution of the therapeutic spot by using a confocal aperture that is significantly smaller One solution uses two adjacent confocal series of apertures 200 and 202, aperture 204 will be smaller but constructed of such material e g Kodak Wratten filter 89B that passes maximally the 792 nm light Th s light then is filtered through the larger confocal aperture 206 The filter 204 is thin and can be placed at a variable distance from aperture 206 This feature can further reduce the small effects of chromatic longitudinal aberration It should be noted that the aiming beam backscatter from the retina is only slightly polarized the specular reflection from the anterior surface of the cornea is polarized, and the intensity has to be strong enough for appropriate detection Hence the advantage of using a modulated external 670 nm diode laser that is pulsed at the retinal location of the therapeutic spot to prevent aliasing The higher intensity is still safe and can be easily detected with a very small confocal aperture

Alternative embodiments of the invention will use other wavelengths for treating the retina The same optical principles however will hold The characteristics of the optical filters have to be adjusted accordingly Also the coatings can be adjusted to accommodate an aiming beam of 635 nm instead of 670 nm For microperimetπc purposes, increased 633 nm transmission would increase the visibility of the fixation light for the subject

IV MAXWELLIAN VIEW CONTROL OPTIONS

It is important to know the entrance position of the Maxwellian view of a reference fixation target or retinal location produced by the scanning lasers 38 40 and the entrance position of the external diagnostic lasers 52 54 with regard to the anatomical pupil and anterior segment of the eye This knowledge is necessary to reconstruct the wavefront aberrations of the eye because the anatomical pupil s a fiducial structure that is used to map these wavefront aberrations With other words 21 each significant entrance position of the external diagnostic beam should be documented together with the entrance position of the scanning laser rays that correspond to a fiducial landmark on the retina The test should be short enough to keep the latter entrance position constant by preventing lateral eye movements A bite-bar or data correction may be necessary if the test duration is longer. Small rotations of the eye, because of fixation instability, will cause this reference fiducial landmark to shift on the retina These shifts however are mostly irrelevant because the distance between such fiducial landmark and the retinal location of the external diagnostic laser beam rather than the absolute position of the external laser beam is taken into consideration for the purpose of calculating wavefront aberrations The above consideration is important the reflectometric method. In the psychophysical method, the subject will make a reference fixation target coincide with the spot of the moving external laser beam 52, 54 through angulation of th s beam with the micromampulator 78 Variations m fixation are averaged out by the subject and do not have to be taken into account. Means and methods to document, verify or change in a controlled manner the entrance locations of the Maxwellian view have been documented extensively in United States Patent N° 5,568,208, issued October 22, 1996, entitled 'Modified scanning laser ophthalmoscope for psychophysical applications" and United States patent application Ns 9/033900, filed March 1, 1989, entitled "Maxwellian view and modulation control options m the scanning laser ophthalmoscope ' , both herein incorporated by reference They typically include a beamsplitter, CCD camera, and equipment for analyzing the video illustrating the location of the Maxwellian view In the absence of active control of the entrance location, a bite-bar would be necessary to maintain and document a specific entrance location The Maxwellian view control is much less important for microphotocoagulation purposes and can be omitted in this case It can also be omitted f the test is short and alignment is verified with the help of the Purk je images These images are for example provided by a number of entrance locations of the external diagnostic laser beam when no polarization is used m the detection pathway

V THE OVERLAY FRAMEGRABBER CARDS AND IMAGE PROCESSING TECHNIQUES

Indispensable for processing the video that is generated by the scanning laser ophthalmoscope laser sources 38, 40 and external laser source 52, 54, and for the production of graphics that w ll be projected onto the retina, is an overlay frame grabber graphics card 32, schematized m F g. 4 A good example is the Imaging Technology OFG card in a 90 Mhz Pentium PC This overlay frame grabber graphics card 32 can accept four different video input sources, and digitizes the incoming video signals to eight bits of accuracy, at a rate of 60 fields per second (RS-170) . On 22 board frame memory can store two 512 by 480 pixel video frames or one larger 640 by 512 pixel video frame. Two or more overlay frame grabber cards 32, which are I/O mapped, can reside in one computer 34. This versatility is advantageous when combining the signals from a multidetector scanning laser ophthalmoscope, e.g. in simultaneous recording of the aiming laser beam location on the retina witn one detector 28 and the retinal image itself with another detector 28 The analog-to-digital converter of the frame grabber card 32 has programmable negative and positive reference values for calibrating the white and black video signal levels . A look-up table (LUT) controls the input video and can be used for preprocessing contrast and intensity Th s feature is particularly useful in facilitating normalized gray scale correlation, a digital image processing technique further explained It can also be used to separate the aiming beam pixels from noise pixels

An additional four bits per pixel control the instantaneous switching between 16 different output look-up tables for each pixel. Three independent output channels are provided for each imaging board. The output channels generate RS-170 video adapted for pseudo-color display Output LUT programming is a well known solution for creating non-destructive graphic overlays Non-destructive graphic overlays 46, drawn over the incoming video signal, generate the graphics visible in the laser raster of the scanning laser ophthalmoscope and indicate the position on the retina of the aiming laser beam The overlay 46 can be semi-transparent to imitate the look and feel of a real aiming beam when using the slitlamp coagulator In Fig 4, the green output video channel sends the retinal image to the monitor 36, overlaid with graphics indicating the aiming therapeutic laser beam location The blue output channel of the original video signal is transformed into pure graphics. It controls the acousto- optic modulator 44 and defines what is visible to the observer in the scanning laser ophthalmoscope. This is typically a reference fixation target or test stimulus The remaining red output channel can be used for different purposes One option is the control of the acousto-optic modulator to create a pulsating external laser beam 54 An important feature of the overlay frame grabber card is the capability to synchronize frame grabber memory D/A, A/D converters, to the external video source using a phase-locked loop This s important since the timing signals provided by the high speed rotating polygon are slightly irregular

Digital image processing techniques are used for the tracking of a fiducial landmarK in the retinal image as in Fig 5. The overlay frame grabber card 32, or an external faster card connected to the computer 34, can perform this task using for example a technique called two-dimensional normalized gray-scale correlation. Such software is provided by Imaging Technology, Inc, Bedford, Ma In two-dimensional normalized grayscale correlation a characteristic search pattern, such as the branching of retinal 23 vessels or the actual area of treatment is located with the video images provided by a detector 28 of the scanning laser ophthalmoscope. Sub-pixel accuracy is possible and sometimes necessary for the determination of small displacements in the presence of wavefront aberrations A higher resolution imaging board or digital oscilloscope is another obvious solution to help to increase the resolving power beyond 0 1 mill radians , a value desirable for wavefront reconstruction techniques Locating the aiming laser beam on the retina, as in Fig 6, and modulating the aiming beam in an anti-aliased fashion, as in Fig 10, is realized using a combination of foregoing techniques The aiming or diagnostic laser beam location is already approximately known by the computer if it takes into account the mechanical displacement of the joystick-manipulator 78 To facilitate the extent and characteristics of the external aiming or diagnostic laser beam, the reference image m frame memory contains no retinal details as m Fig. 5, for facilitating the tracking of a fiducial landmark on the retina, the fundus image in frame memory is devoid of the therapeutic laser light, as in Fig 6

Thus, the same method of locating an external laser spot on the retina is used to calculate the wavefront aberrations of the complete eye optics, by systematically varying the entrance location of an external aiming laser source across the extent of the anatomical pupil, in a parallel fashion, relative to scanning laser ophthalmoscope The differences in retinal location and shape characteristics of the external laser beam spot on the retina, and optionally a reference location m the scanning laser raster on the retina are image processed Alternatively, the differences in position can be neutralized with an adjustment of the postion of the fixation spot in the scanning laser raster. Well-known Zernike polynomial analysis can then reconstruct the wavefront aberrations from this data of slope determinations of the incident rays at about 30 to 60 positions.

The possibility to register the location of therapeutic applications using an optical biomicroscope equipped with two synchronized CCD cameras has also been discussed Different therapeutic wavelengths can be used by changing the characteristics of the optical filters.

Although the description of the invention contains many specifications, these should not be construed as limiting the scope of the invention but as merely providing an illustration of the presently preferred embodiment of th s invention Other embodiments of the invention including additions, subtractions, deletions, or modifications of the disclosed embodiment will be obvious to those skilled m the art and are withm the scope of the following claims The scope of the invention should be determined by the appended claims and their legal equivalents, rather than by the examples given.

Claims

24 CLAIMSI claim
1. A combination of a confocal scanning laser ophthalmoscope and external therapeutic laser source, for delivering a therapeutic laser beam of said laser source to the retina of an eye comprising the elements of
A said scanning laser ophthalmoscope, having at least one laser beam of a first wavelength that is scanned through a pivot point, and first detector means for obtaining a video image of said retma with said first detector of said scanning laser ophthalmoscope ,
B said external therapeutic laser source comprising an aiming beam laser of second wavelength and said therapeutic laser beam, further including a means to focus said therapeutic laser beam and said aiming beam, and supporting electronics controlling the size duration and intensity of sa d therapeutic laser beam on the retma,
C. means for optically coupling said scanning laser ophthalmoscope with said therapeutic laser source including a beam splitter on which a coating is applied to permit said at least one laser beam and said aiming beam to be combined before entering said eye
D second detecting means m said scanning laser ophthalmoscope comprising second detector and optical means for detecting by preference said second wavelength said second detecting means generating a video image that is synchronized with a video image produced by said first detector of said scanning laser ophthalmoscope,
E digital image processing means comprising of a computer with a frame grabber card capable of generating overlay graphics, said frame grabber card further including means for synchronizing the video images produced by said first and said second detector to timing signals provided by said scanning laser ophthalmoscope, and output means capable of documenting the location of said aiming beam on the retina,
F opto-mechanical means for coupling said scanning laser ophthalmoscope with said therapeutic laser source including a succession of mirror interfaces and structural support means joined together to move said aiming beam in such manner that a pivot point is created for said therapeutic beam, coincident with said pivot point of said scanning laser ophthalmoscope 25 whereby optimal conditions of visualization are created to continuously observe the ret a on a monitor and freely position said aiming beam on the retma, activate said therapeutic laser source for a variable amount of time while observing and registering with said computer the position of said aiming beam on the retma
2. A combination of a confocal scanning laser ophthalmoscope and external therapeutic laser source, for delivering a therapeutic laser beam of said laser source to the retma of an eye according to claim 1, further comprising interrupting means including electronic circuitry to attenuate said therapeutic laser beam, said interrupting means allowing the attenuation of said therapeutic laser beam faster than human reaction time would allow in case of misalignment of said aiming beam on the ret a as registered with said digital image processing means
3. A combination of a confocal scanning laser ophthalmoscope and external therapeutic laser source for delivering a therapeutic laser beam of said laser source to the retma of an eye according to claim 1, further comprising modulating means for a laser source of visible wavelength m said scanning laser ophthalmoscope, to create graphical stimuli in the visible laser raster of said scanning laser ophthalmoscope, whereby a fixation target is provided for the observer facilitating the delivery of said aiming beam to the retma
4 A combination of a scanning laser ophthalmoscope and external diagnostic laser source, for delivering a diagnostic laser beam of said laser source to the retma of an eye, to determine the wavefront aberrations of the optics of said eye, comprising the elements of
A. said scanning laser ophthalmoscope, having laser beam of a first wavelength that is scanned through a pivot point, and first detector means for obtaining a video image of said retma of said eye;
B reference laser beam of a second wavelength withm said scanning laser ophthalmoscope, with modulating means to create a reference spot on said retma,
C. said external diagnostic laser source, comprising said diagnostic laser beam of a third wavelength, said diagnostic laser beam producing a diagnostic spot on said ret a, further including a means to focus said diagnostic laser beam, and electronical means for controlling the size, duration and intensity of said diagnostic laser beam on the retma,
D. means for optically coupling said scanning laser ophthalmoscope with said diagnostic laser source including a beam splitter on which a coating s applied to permit said laser beam of said first wavelength, said reference laser beam of second 26 wavelength and said diagnostic laser beam of third wavelength to be combined before entering the eye,
E second detecting means in said scanning laser ophthalmoscope comprising second detector and optical means for detecting by preference said third wavelength said second detecting means generating a video image that is synchronized with a video image produced by said first detector of said scanning laser ophthalmoscope,
F means for stabilizing the position of said eye relative to said scanning laser ophthalmoscope ,
G opto-mechanical means for coupling said scanning laser ophthalmoscope with said diagnostic laser source including a succession of optical interfaces and structural support means joined together to move said diagnostic laser beam such manner that a multitude of entrance locations is created for said diagnostic laser beam,
H digital image processing means comprising of a computer with a frame grabber card capable of generating overlay graphics said frame grabber card further including means for synchronizing the video images produced by said first and said second detector to timing signals provided by said scanning laser ophthalmoscope and output means capable of documenting the location of said diagnostic laser beam and said reference laser beam on the retma, whereby said diagnostic spot and said reference spot are documented on said retma for each said entrance location to derive the wavefront aberrations of the eye optics
5 The scanning laser ophthalmoscope for the derivation of the wavefront aberrations of the eye optics according to claim 4 further comprising the improvement of having mechanical means to angulate said external diagnostic laser beam for each said entrance location to superimpose said diagnostic spot with said reference spot on said ret a for each said entrance location
6 The scanning laser ophthalmoscope for the derivation of the wavefront aberrations of the eye optics according to claim 4 further comprising the improvement of having means for visualizing the anterior segment of the eye thereby allowing the registration of said entrance location of said external diagnostic laser beam in the presence of eye movements
7 The scanning laser ophthalmoscope for the derivation of the wavefront aberrations of the eye optics according to claim 4 using a multiple element solid state laser to create said multitude of entrance locations for said diagnostic laser beam into said eye 27
8. A combination of a confocal scanning laser ophthalmoscope and external therapeutic laser source, for delivering a therapeutic laser beam of said laser source to the retma of an eye according to claim 1 further having a second modulating means for said therapeutic laser beam, said second modulating means capable of pulsing said therapeutic laser beam.
9. A combination of a confocal scanning laser ophthalmoscope and external therapeutic laser source, for delivering a therapeutic laser beam of said laser source to the retma of an eye according to claim 1 further having a third modulating means for said aiming laser beam, said third modulating means capable of pulsing said aiming laser beam under control of said digital image processing means so that no aliasing occurs on said video image produced by said second detecting means and whereby power of said aiming beam can be augmented without harming said retma of said eye.
10. A combination of a scanning laser ophthalmoscope and external diagnostic laser source, for delivering a diagnostic laser beam of said laser source to the retma of an eye, to determine the wavefront aberrations of the optics of said eye according to claim 4 further incorporating a second modulating means for said diagnostic laser beam, said second modulating means capable of pulsing said diagnostic laser beam under control of said digital image processing means so that no aliasing occurs on said video image produced by said second detecting means and whereby power of said diagnostic beam can be augmented without harming said retma of said eye
PCT/US1999/009911 1996-11-22 1999-05-07 Scanning laser ophthalmoscope for microphotocoagulation with minimal optical aberrations WO1999058047A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US09/075,239 1998-05-09
US09075239 US5943117A (en) 1996-11-22 1998-05-09 Scanning laser ophthalmoscope for retinal microphotocoagulation and measurement of wavefront aberrations
US09118767 US5892569A (en) 1996-11-22 1998-07-18 Scanning laser ophthalmoscope optimized for retinal microphotocoagulation
US09/118,767 1998-07-18

Applications Claiming Priority (1)

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EP19990921721 EP1082048A1 (en) 1998-05-09 1999-05-07 Scanning laser ophthalmoscope for microphotocoagulation with minimal optical aberrations

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EP1354573A1 (en) * 2002-04-08 2003-10-22 Lumenis Inc. System, method and apparatus for providing uniform illumination
WO2003028548A3 (en) * 2001-10-03 2004-05-06 Vasyl Molebny Method of measurement of wave aberrations of an eye
EP1452126A1 (en) * 2001-11-09 2004-09-01 Kabushiki Kaisha TOPCON Device for measuring optical characteristic of eye
EP1850730A2 (en) * 2005-02-07 2007-11-07 Ocutronics, LLC Hand held device and methods for examining a patient's retina
WO2007073848A3 (en) * 2005-12-15 2007-11-29 Franz Fankhauser Device measuring eyes with the aid of dynamic light scattering
US7438713B2 (en) 2001-03-22 2008-10-21 Lumenis, Inc. Scanning laser handpiece with shaped output beam
WO2009026417A1 (en) * 2007-08-23 2009-02-26 Bausch & Lomb Incorporated Eye illumination apparatus and method
WO2011151040A1 (en) * 2010-06-04 2011-12-08 Carl Zeiss Meditec Ag Ophthalmology appliance for photocoagulation or phototherapy, and method for operating such an appliance
EP2386243A3 (en) * 2006-07-07 2012-09-12 OD-OS GmbH Ophthalmoscope
US8346345B2 (en) 2004-01-21 2013-01-01 University Of Washington Methods for assessing a physiological state of a mammalian retina

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7438713B2 (en) 2001-03-22 2008-10-21 Lumenis, Inc. Scanning laser handpiece with shaped output beam
US7824396B2 (en) 2001-03-22 2010-11-02 Lumenis Ltd. Scanner laser handpiece with shaped output beam
WO2003028548A3 (en) * 2001-10-03 2004-05-06 Vasyl Molebny Method of measurement of wave aberrations of an eye
EP1452126A1 (en) * 2001-11-09 2004-09-01 Kabushiki Kaisha TOPCON Device for measuring optical characteristic of eye
EP1452126A4 (en) * 2001-11-09 2009-04-15 Topcon Corp Device for measuring optical characteristic of eye
US7263255B2 (en) 2002-04-08 2007-08-28 Lumenis Inc. System, method and apparatus for providing uniform illumination
EP1354573A1 (en) * 2002-04-08 2003-10-22 Lumenis Inc. System, method and apparatus for providing uniform illumination
US8346345B2 (en) 2004-01-21 2013-01-01 University Of Washington Methods for assessing a physiological state of a mammalian retina
EP1850730A4 (en) * 2005-02-07 2010-02-10 Ocutronics Llc Hand held device and methods for examining a patient's retina
EP1850730A2 (en) * 2005-02-07 2007-11-07 Ocutronics, LLC Hand held device and methods for examining a patient's retina
WO2007073848A3 (en) * 2005-12-15 2007-11-29 Franz Fankhauser Device measuring eyes with the aid of dynamic light scattering
EP2386243A3 (en) * 2006-07-07 2012-09-12 OD-OS GmbH Ophthalmoscope
US8157378B2 (en) 2007-08-23 2012-04-17 Bausch & Lomb Incorporated Eye illumination apparatus and method
WO2009026417A1 (en) * 2007-08-23 2009-02-26 Bausch & Lomb Incorporated Eye illumination apparatus and method
WO2011151040A1 (en) * 2010-06-04 2011-12-08 Carl Zeiss Meditec Ag Ophthalmology appliance for photocoagulation or phototherapy, and method for operating such an appliance

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