This invention relates to a method of ophthalmic treatment and a laser instrument designed for use by ophthalmologists for performing the treatment. In particular, the invention relates to a laser system and treatment method for selective ophthalmic laser treatment of ocular structures and individual retinal layers, such as the retinal pigmented epithelium (RPE).
Ophthalmic laser systems are being used for an ever increasing variety of procedures for treating various eye disorders. Equipment and methods for treating glaucoma and performing secondary cataract surgery have been described in our co-pending international application WO 04/027487 titled “Ophthalmic Laser System”. We have also described a laser system designed for Retinal Photocoagulation, Pan Retinal Photocoagulation, Photocoagulation for Macular Degeneration and Laser Trabeculoplasty in published international application number WO 02/083041.
Although these laser systems have proven to be extremely useful for their intended purpose, it has been realised that a number of ophthalmic procedures may cause unintended collateral damage to parts of the eye. For instance, many treatments rely upon heating to cause photocoagulation in a target area. Unfortunately these methods generally rely upon the appearance of a visible lesion on the surface of the eye as an indication that the desired photocoagulation has occurred within the target area. Because a large proportion of the laser radiation is absorbed in layers below the surface of the retina, considerable damage is done to sub-surface retinal layers before a visible lesion appears. While many retinal diseases can be treated by this method the benefit obtained must be carefully considered in relation to the lesions and sub-surface damage that occurs, which can result in a severe loss of visual acuity.
Several retinal diseases are thought to be initiated by a reduction in the correct functioning of the RPE and studies have shown that the function of the retina can be improved by damaging the sub-surface mono-layer of cells in the RPE layer and then allowing them to rejuvenate, but only if it can be done without damaging the overlying neuro-retinal layers or the underlying choroid. The photoreceptors in the neuro-retina are particularly sensitive to damage, however 50% of the incident light that falls on the retina is absorbed in the RPE layer due to their high melanosome content. This makes it possible to selectively heat the RPE layer by applying suitable laser energy, however it is difficult to confine the temperature rise within the RPE to a level that can damage the RPE cells without damaging the photoreceptors.
Attempts have been made (Clinical Applications of the MicroPulse Diode Laser, Moorman C M, Hamilton A M P, Eye 13:145-150, 1999) to selectively treat the RPE layer using a number of 810 nm laser pulses which are about 100 μs in duration at energy levels which did not cause visible lesions. While the objective of this was to spatially confine the temperature rise within the RPE layer, the duration of the pulses is thought to be too long to prevent damage to the neuro-retinal structures immediately adjacent to the RPE layer.
To attempt to overcome this limitation a number of methods have been developed to monitor the effect of the laser treatment at the target area in an effort to provide the ophthalmologist with an accurate treatment end-point which causes the least collateral damage. One such method is described in U.S. Pat. No. 6,540,391 assigned to Iridex Corporation, which describes an interferometric technique to monitor the changes in the target area during the course of a treatment. The method is difficult to implement and limited in application.
The same company describes an intra-operative monitoring system that measures focal electroretinograms during the course of laser treatment to provide a feedback measure to the physician. The approach is described in U.S. Pat. No. 6,733,490. As with the interferometric technique, the measurement and analysis of focal electroretinograms is difficult to implement and of limited application.
A third approach described by Iridex Corporation is described in international patent publication number WO 04/026099. In this patent application they propose a technique in which light scattering is monitored during a treatment on the basis that changes in scattering intensity correlate with temperature dependent changes at the treatment site.
Each of the techniques described by Iridex Corporation add cost and complexity and do not address the fundamental problem of thermal damage to the photoreceptors caused by the relatively long laser pulse duration used.
An alternate approach is presented by Roider, Brinkmann, Wirbelauer, Laqua and Birngruber in J. Ophthalmol. 2000 84:40-47 in which a series of 527 nm laser pulses of 1.7 μs duration are used to selectively treat the RPE layer while avoiding unwanted collateral effects. The use of this pulse duration allows rapid temperature rise in the melanosites within the RPE cells but limits heat diffusion to the photoreceptors. This approach is based on the work of Birngruber in U.S. Pat. No. 5,302,259 which describes a method of coagulating material based on selective absorption of energy. Although Birngruber describes the general principle in his patent, he does not provide description of how to put this into practical effect for ophthalmic laser treatment but does show in his paper that selective ophthalmic laser treatment applications are possible by separately evaluating each patient and then carefully balancing a variety of laser parameters to achieve the optimal treatment.
It is evident that the concepts described by Birngruber must be refined to achieve a practical device that can be routinely used for ophthalmic laser treatments.
An attempt at such a refinement is found in U.S. Pat. No. 5,549,596 in the name of Latina. Latina applies the Birngruber technique to selectively target pigmented ocular cells to treat glaucoma, intraocular melanoma and disease of the RPE. The claims of the Latina patent describe the use of a radiant exposure of 0.01 J/cm2 to 5 J/cm2 using one or more pulses which are 1 ns to 2 μs in duration and using a wavelength that is absorbed more in the pigmented cells than in the non-pigmented cells.
The Latina technique has been successfully applied in the treatment of glaucoma using a procedure known as selective laser trabeculoplasy (SLT). SLT treatment is applied to areas of melanin concentration in the trabecular meshwork (TM) in order to reduce the intraocular pressure. The TM can be directly accessed by the laser radiation without the need to pass through any overlying tissue so in this case the radiant exposure range of 0.01 J/cm2 to 5 J/cm2 is adequate, however clinical results have shown that this radiant exposure range is insufficient to effectively treat the RPE layer and that the combination of other laser pulse parameters such as the number of pulses and the pulse repetition rate are critical in achieving effective coagulation of the RPE layer while sparing the neuro-retina and choroid.
It appears from the published work on selective laser trabeculoplasy and sub-threshold retinal laser treatment that careful control of laser energy delivery can facilitate a new level of ophthalmic laser treatment precision and sophistication. While some laser systems allow partially selective RPE treatment, and the effectiveness of highly selective treatment have been experimentally demonstrated in a limited manner, there are no laser systems or treatment protocols that can produce the full range of treatment options required in a manner that can be readily understood by the ophthalmologist, so that the full potential of selective ophthalmic laser treatment can be realized.
In one form, although it need not be the only or indeed the broadest form, the invention resides in an ophthalmic laser system comprising:
The laser module of the ophthalmic laser system suitably incorporates a pulsed laser and a pulse gating element, said pulsed laser producing a train of pulses and said pulse gating element selecting bursts of pulses from said train of pulses.
The pulsed laser is suitably a Q-switched solid state laser operating in the wavelength range from 500 nm to 750 nm with a pulse repetition rate from 1 kHz to 500 kHz, and a pulse duration from 0.1 μs to 40 μs.
The ophthalmic laser system may further comprise feedback means that provides treatment feedback to the control module for dynamic control of the laser module.
In a further form the invention resides in a method of ophthalmic laser treatment including the steps of:
The method is preferably applied to the retinal pigmented epithelium layer in a procedure such as Selective Retinal Therapy (SRT).
The method may further include the step of selecting treatment target values, if these have been pre-determined, and displaying the target treatment values with the calculated sensitivity and treatment time. The treatment target values may be derived from patient dependant pre-set variables and measured values.
The invention may further include using a visible lesion threshold to determine estimated optimal laser treatment parameters by:
Further manual adjustment of treatment parameters by a user may be required. Once the estimated optimal laser treatment parameters are determined the method proceeds as above.
The invention may further include using feedback from external measurement devices, which are designed to indicate the effectiveness of ophthalmic laser treatment, to allow manual or automatic adjustment of laser treatment parameters to optimize the treatment by:
To assist in understanding the invention, preferred embodiments will be described with reference to the following figures in which:
Referring to
A preferred embodiment of the laser module 2 is shown schematically in
The laser operates between 500 nm and 750 nm. The appropriate solid state active medium is selected for the required wavelength. An active medium of Nd:YAG can produce 532 nm, 561 nm or 659 nm and Nd:YLF can produce 527 nm. A typical laser for the invention is a frequency doubled Nd:YAG laser operating with the following parameters:
The pulse gating element allows the required combination of pulses in a burst to be delivered to the treatment zone via the optics bench module and the delivery module. The required combination of pulses is determined by the system control module in response to the user settings. The pulse gating element is typically an electro-optic switch. Typical operating parameters for use with the laser head described above are:
For example, when the intra-cavity Q-switch frequency is 30 kHz (rep rate of 33.3 μs per pulse ) and the total treatment time is 100 ms, the laser will output about 3000 pulses. The pulse gating element can then be operated to pass any combination of pulses in a burst. It could, for example, be controlled to pass 3 pulses every 1 ms thus giving about 100 bursts with 3 pulses per burst.
The optical bench 26 has optics for coupling the output from the laser 22 and gating element 24 to the optical fiber 6 via optical fiber coupler 27. It also includes a safety shutter 28 that blocks the optical fiber coupler under control of the control module 4. An aiming laser 29 may be provided on the optical bench 26 and aligned to be coaxial with the output of the laser 22.
A suitable delivery module 3 is shown in
The micromanipulator lens is mounted on a pivotable arm, wherein pivoting of said lens about an optic axis translates to movement of a focused output of the optical fibre at the treatment zone 5.
The position of the optical zoom 35 can be adjusted by the user to set the spot size at treatment zone 5 and the zoom position is monitored by the control module 4 for use in setting the laser parameters to deliver a desired total radiant energy. The spot size determines the total radiant energy that is delivered at the treatment zone. In some embodiments the optical zoom 35 may also be automated and set directly by the control module 4. Persons skilled in the field will be aware of various linear drive and stepper motor options that are useful for automating the optical zoom.
The control module is shown in greater detail in
The control module 4 also incorporates a power supply 44 that converts mains power 45 to all voltages required in the control module 4, delivery module 3 and the laser module 2. Various interlocks 46 ensure safe operation of the system.
In use, the user can select various treatment modes via the input 43 including, selective RPE treatment, selective trabecular meshwork treatment, Iridotomy, and non-selective retinal coagulation. The system control processor 41 displays the selected treatment parameters and likely treatment outcome in a manner that suits the selected treatment mode and then, on command of the user, delivers the selected treatment as a series of laser pulses that are controlled by the intra-cavity Q-switch within the laser module and the pulse gating element.
The selective RPE treatment mode is the most demanding mode as the target RPE layer is a sub-surface layer. Spatial confinement of the temperature rise in the RPE layer is required to produce selective photo-coagulation, which requires careful control of the energy delivery. The laser pulse duration must be well below the thermal relaxation time of the target structure to avoid heat diffusion into adjacent structures which could cause collateral damage. This results in the need to deliver the high energy levels that can produce localized photo-coagulation in a very short time period.
To avoid inducing mechanical effects such as cavitations and micro-explosions due to the resulting high energy gradients it is preferable to deliver the energy as a series of very short duration bursts of laser pulses, with a relatively low repetition rate, which have an additive thermal effect. For example, selective RPE treatment may require up to 300 μJ pulses with 1 μs duration, which are repeated every 2 ms. Rather than deliver these as single high energy pulses, the laser system presented is able to deliver bursts of closely spaced laser pulses which can have the same additive effect as a single high energy pulse. The delivery of pulse bursts reduces the cost and complexity of the laser system and further reduces the risk of unwanted mechanical effects at the treatment zone. The intra-cavity Q-switch within the laser module produces pulses at the pulse burst rate, while the pulse gating module allows the burst repetition rate and the number of pulses per burst to be controlled.
The radiation is delivered to the retina and other ocular structures in bursts of laser pulses of a wavelength between about 500 nm and about 750 nm, which is preferentially absorbed more in the target layer or ocular structure than in adjacent areas for selective treatment modes, with pulse durations of between 0.1 μs and 40 μs, energy per pulse up to approximately 300 μJ , pulse repetition rate of between 1 kHz and 500 kHz, pulse burst repetition rate of between 0.05 kHz, and 5 kHz, pulses per burst of between 1 and 100 pulses, and between 1 and 500 pulse bursts. By selecting the number of laser pulse bursts, the burst repetition rate, the number of pulses per burst, the laser pulse intensity and treatment area to achieve a total radiant exposure of between about 1 and about 300 Joules/cm2, it is possible to heat the target layers or ocular structures within the selected treatment area to a temperature that causes damage to it without causing a temperature rise that can damage the adjacent layers or ocular structures. Alternatively, other combinations of pulse bursts, pulse burst intervals and pulse energy levels can be chosen to produce other selective or non-selective photo-coagulation effects to suit other treatment modes.
By choosing a treatment radiation wavelength which is close to the lower end of the stated range of 500 nm to 750 nm, the minimum treatment energy can be used because of maximum absorption within the melanin of the RPE layer, however the wavelength of the treatment radiation can also be chosen to minimize the interference from overlying retinal vasculature. A wavelength which is close to the higher end of the stated range, such as 670 nm, can be used which has minimum absorption in oxygenated hemoglobin, which will result in more consistent energy delivery to the treatment spot area of the RPE layer and reduce the chance of retinal vascular damage.
In a preferred embodiment the laser is employed for a method of treating the retinal pigmented epithelium (RPE) layer. To obtain selective photocoagulation of the RPE layer a large amount of energy must be delivered in a short time, and then repeated a number of times with a relatively large time between pulses. Typical values are a wavelength of 532 nm, 1 μs pulse duration, 3 pulses per burst, 30 kHz pulse repetition rate, 50 μJ pulse energy, 500 Hz pulse burst repetition rate and a total of 100 bursts. Using a 200 micron diameter treatment spot this will produce a total radiant exposure of about 48J/cm2, as shown in
Selective RPE treatment is dependant on the relative laser radiation absorption ratio between the neuro-retina and RPE layer and the physical characteristics of the layers, which can vary over a wide range from patient to patient. In addition, to achieve the selective coagulation of the thin, sub-surface RPE layer without causing collateral damage to the overlying neuro-retina requires a careful balance of interdependent treatment parameters. This makes it very difficult for the ophthalmic surgeon to choose the optimum treatment parameters and understand the combined effects. The interdependent parameters include treatment spot size, pulse width, pulse amplitude, pulse repetition rate and the total number of pulses delivered. All these parameters must be chosen to optimize the therapeutic window, and this must be judged against the total treatment time. If the treatment time which results from the parameters chosen to optimize the therapeutic window is too long the treatment effectiveness can be compromised by patient eye movement.
To allow the RPE layer of the retina to be selectively damaged by laser radiation, while sparing the overlying neuro-retina and underlying choroid, the laser treatment parameters must be carefully chosen. The relationship between these parameters and the resulting thermal effects within retinal layers is not easily understood, however it is possible to calculate these relationships in a way that can predict the likely clinical outcome and enable the impact of any changes to the treatment parameters to be assessed and presented to the ophthalmic surgeon in a meaningful and easily interpreted manner.
The aim of selective retinal treatment is to reach the cell rupture temperature within the RPE layer, by applying a series of laser pulses, while limiting the temperature in the neuro-retina immediately next to the RPE layer to the lowest possible value at the end of the laser treatment. The ratio between the RPE layer temperature and the neuro-retina temperature immediately next to the RPE layer is considered in this context to be the therapeutic window (TW). The greater the difference between the RPE temperature and the neuro-retina temperature the more selective the effect will be and therefore the wider the therapeutic window is considered to be. The thermal modelling principles are described in greater detail below with reference to the flowchart of
Calculation of the therapeutic window is carried out as follows:
where
tRPE is the cumulative temperature rise in the RPE melanin pigments caused by energy absorption during laser pulsing minus cumulative temperature drop between laser pulses due to diffusion;
tNR is the cumulative temperature rise in the NR within the treatment zone at a point adjacent to the RPE layer caused by energy absorption during laser pulsing and heat diffusion from the RPE layer minus cumulative temperature drop between laser pulses due to diffusion; and
γRPE/NR is a pre-set scaling factor to account for the absorption ratio between the RPE and the NR. The scaling factor is chosen to give an approximately equal weighting to the RPE and NR temperatures.
The cumulative temperature rise in the RPE melanin pigments is dependant on:
The cumulative temperature drop in the RPE melanin pigments due to diffusion is dependant on:
The cumulative temperature rise in the NR is dependant on:
The cumulative temperature drop in the NR due to diffusion is dependanton:
By displaying the relative TW based on the parameters selected by the user, the impact of any changes to the parameters can be quickly assessed. In addition, the likely effect over the course of the pulse train can be graphically displayed so that the relative changes in the RPE and NR temperatures, that result in the TW value, can be separately viewed.
Finding the optimum therapeutic window can involve changes to both the pulse repetition rate and the number of pulses delivered, which will affect the total treatment time. If the total treatment time is too long the treatment can be compromised by patient eye movement which can result in an insufficient treatment dose, particularly in the periphery of the treatment area. By determining and presenting the total treatment time to the user, along with the therapeutic window, the two factors can be assessed to give the best overall result.
The total treatment time can be calculated as follows:
Total treatment time=Total number of pulse bursts×Pulse burst repetition rate
By using this method the complex relationships between all laser parameters including, pulse duration, pulse amplitude, pulse repetition rate, total number of pulses and treatment spot size can be readily assessed by the ophthalmic surgeon in terms that directly relate to the objective of the treatment.
The parameters required for the calculation of likely temperature effects can be calculated from estimations of the thermal capacity and photoabsorption of the relevant tissues. The calculations are programmed into the system control processor in the form of an analysis algorithm within a package of treatment aid software which includes a graphical user interface, so that the likely treatment effect can be presented to the user to assist in the optimization of the treatment outcome. In order to assist understanding of the calculations required an example of a graphical user interface is shown in
Pre-set treatment values are set in panel 69. The example in
It will be appreciated that
The interactive treatment aid software may include pre-programmed information on the normal range of parameter settings used for each treatment mode, derived from clinical trials, in order to display the treatment limits and advise the user if these are exceeded. For example,
As mentioned above, the invention includes the ability to set and display treatment targets which may be derived from post treatment measurements of treatment effectiveness, internal estimated targets based on scaled visible treatment thresholds or external measurement systems of treatment effectiveness. For RPE treatment the targets would typically be in the form of a target minimum temperature rise value for the RPE layer to achieve cell damage, and a maximum target temperature rise value for the adjacent neuro-retina which should not be exceeded to avoid collateral damage. These target levels, shown in
Other treatment modalities require similar displays that show other relevant parameters.
Once the user has selected the treatment parameters the user locks in the total radiant exposure value via the control module, so that changes to the treatment spot size, which may become necessary during treatment of different areas, cause an automatic adjustment of the pulse energy to maintain the selected total radiant exposure.
From the above discussion it can be seen that the ophthalmic laser system is used in a method of carrying out a number of ophthalmic procedures such as Selective Retinal Therapy (SRT), Selective Laser Trabeculoplasty (SLT), Iridotomy and non-selective retinal coagulation. The method of treating the retinal pigmented epithelium layer of the retina of a patient using the SRT technique includes the steps of:
Steps 4 and 5 are displayed using the graphical user interface of
As mentioned earlier, the method of treating the retinal pigmented epithelium layer of the retina of a patient can be expanded to use a visible lesion threshold to determine approximate selective RPE treatment parameters including the steps of:
The level of pigmentation in the RPE will directly influence the treatment parameters required to achieve selective RPE treatment. In human eyes the variation in average RPE pigmentation is about two fold and the method described in steps 4 to 8 above is designed to provide a means of compensating for this variation and providing the ophthalmic surgeon with estimated settings for effective selective RPE treatment that are chosen to suit each patient. By using the same duration laser pulses, but increasing the number of pulses per burst, a visible lesion can be produced in the periphery of the retina where no vision loss will occur. The total radiant exposure required to reach the threshold point where a visible lesion occurs will be approximately proportional to the individual level of RPE pigmentation in each patient so by applying a suitable scaling factor suitable selective RPE treatment parameters can be determined. An in-built parameter optimizing algorithm pre-sets the recommended treatment parameters, and then the user adjusts the setting manually if required. The algorithm will also display the calculated target temperatures for the RPE layer and adjacent neuro-retina so that the user can select other settings if required which will achieve the same selective temperature effects.
The value of the scaling factor can be determined by checking the treatment effectiveness using fluorescein angiography. A two fold variation in pigmentation also occurs between the fovea and paramacular regions with the fovea being the most heavily pigmented region. The scaling factor can also be adjusted to allow for this variation.
Another variation of the treatment method uses feedback from external measurement devices, which are designed to indicate the effectiveness of RPE selective treatment, to allow manual or automatic adjustment of treatment parameters to optimize the treatment including the steps of:
The invention is not limited to treatment of the retinal pigmented epithelium. Another application is treatment of the trabecular meshwork (TM) to lower the intra-ocular pressure using a procedure known as Selective Laser Trabeculoplasty (SLT), which is a treatment for open-angle glaucoma. Typical values are a wavelength of 532 nm, 1 μs pulse duration, 3 pulses per burst, 30 kHz pulse repetition rate, 50 μJ pulse energy, 1 kHz pulse burst repetition rate and a total of 50 bursts. Using a 200 micron diameter treatment spot this will produce a total radiant exposure of about 24 J/cm2. The treatment would be repeated in about 50 spots around 180 degrees of the trabelular meshwork.
Melanin pigmented cells are contained within the trabecular meshwork which is directly accessible for laser treatment. The aim of the procedure is to selectively damage the pigmented cells while leaving the surrounding beams of the trabecular meshwork intact. While the overall method described for selective RPE treatment would be followed, the analysis algorithm, the information regarding normal treatment ranges and the method of determining treatment targets are adapted to suit selective trabecular meshwork treatment. By careful selection of the number of pulse bursts, the energy per pulse and the intervals between bursts, the selective damage to pigmented cells can be carried out in a far more controlled manner than with the delivery of a single high energy pulse.
Another treatment mode would be non-selective retinal coagulation which can be used to perform the well established retinal photo-coagulation tasks which often result in a visible lesion. Typical values are a wavelength of 532 nm, 1 μs pulse duration, 500 pulses per burst, 30 kHz pulse repetition rate, 50 μJ pulse energy, 60 Hz pulse burst repetition rate and a total of 3 bursts. This will produce a pseudo-CW mode which will deliver about 1.6W for 50 ms. When this mode of operation is selected the software will produce a simplified display which allows the user to select the output power and duration, with automatic conversion of the pulsing regime to suit.
Another treatment mode would be iridotomy which is a laser treatment for angle-closure glaucoma. The aim is to produce a hole in the iris to allow free flow of aqueous humor between the posterior and anterior chambers. This is a non-selective procedure with visible tissue effect so when this mode is selected the software will produce a simplified display showing normal treatment ranges and recommended pulse configurations.
The invention has been described primarily with reference to the particular embodiment of treating the retinal pigmented epithelium layer of the retina. It will be appreciated that other embodiments are envisaged within the spirit and scope of the invention.
Number | Date | Country | Kind |
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2004904884 | Aug 2004 | AU | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/AU05/01273 | 8/24/2005 | WO | 2/26/2007 |