System and method for thermally and chemically treating cells at sites of interest in the body to impede cell proliferation

A system and method for treating cells of a site in the body, such as at a lens capsule or choroid of an eye. The system and method employs an energy emitting device, and a positioning device, adapted to position the energy emitting device at a position in relation to the cells at the site in the body, such as the cells of the choroid or the lens capsule, so that energy emitted from the energy emitting device heats the cells to a temperature which is above body temperature and below a temperature at which protein denaturation occurs in the cells, to kill the cells or impede multiplication of the cells. The energy emitting device can also include a container containing a heated fluid that can include indocyanine green, which heats the cells to the desired temperature. Alternatively, the energy emitting device can include a laser diode, or a probe that emits radiation, such as infrared or ultraviolet radiation, laser light, microwave energy or ultrasonic energy. The system and method can further employ a material delivery device that can be unitary with or separate from the energy emitting device, an can provide a material, such as indocyanine green, to the cells at the site of interest. A light emitting device can be controlled to direct light onto the site of interest to activate the material present at the cells to alter a physical characteristic of the cells.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a system and method for treating cells at a site in the body, such as at a lens capsule or choroid of an eye, thermally and, if desired, chemically. More particularly, the present invention relates to a system and method for treating cells at a site in the body, such as at a lens capsule of an eye, by applying energy to the cells to heat the cells to a temperature which will kill the cells or impede cell multiplication without causing protein denaturation to occur in the cells, and, if desired, by further exposing the cells to a material which alters a physical characteristic of the cells to kill the cells or further impede cell multiplication.

2. Description of the Related Art

Several techniques currently exist for treating cells at a selected site in the body with heat or chemicals to kill or impede multiplication of those cells to prevent undesired cell proliferation. For example, numerous types of chemotherapy drugs exists which, when injected into a tumor or delivered systemically to a patient, attack and kill cancerous cells to prevent them from further multiplying.

Radiation techniques can also be used to kill cancerous or other undesired cells. That is, when cells are heated to a temperature of about 5° C. or more above the normal body temperature of 37° C., cell death begins to occur. Applying radiation to a localized site in the body, such as a tumor or other area containing undesired cells, can heat the cells at the site to temperatures in excess of 60° C. Such high temperatures cause a phenomenon known as protein denaturation to occur in the cells, which results in immediate cell death. Accordingly, radiation therapy has been suitable in successfully treating certain types of cancers and other diseases involving uncontrolled cell growth.

Other types of heating techniques, such as the use of probes or catheters to provide localized heat to a site of interest also exist. Like radiation therapy, these techniques also heat the cells to a high enough temperature to cause protein denaturation in the cells to thus kill the cells quickly.

In addition, it is also known to use photosensitive chemicals to kill cells at certain sites of interest in the body. For example, a photosensitive chemical can be injected directly into a site of interest to expose cells at that site to the chemical. A light emitting source which emits light at a wavelength that will activate the photosensitive chemical is then focused on the site of interest. Accordingly, the light activates the photosensitive chemical that has been absorbed by or is otherwise present in the cells of interest. The activated chemical kills the cells, which thus prevents undesired cell proliferation.

Although the techniques mentioned above can be suitable for preventing certain types of cell proliferation and certain sites in the body, several drawbacks with these techniques exist. For example, often the use of chemotherapy drugs alone to treat a tumor or cancerous site is insufficient to kill the undesired cells. Moreover, the chemotherapy drugs also kill many normal healthy cells along with the cancerous cells, which can adversely affect the patient's health.

The use of radiation in conjunction with chemotherapy can have a more detrimental effect on the cancerous cells. However, as with chemotherapy, radiation often kills normal healthy cells, such as those in front of or behind the site of interest, along with the cancerous cells. Moreover, the intense heating of the cells can cause the cells to coagulate and thus block the capillaries at the site of interest. The blocked capillaries therefore prevent chemotherapy drugs from reaching the site of interest.

In addition, is it not known to use the above techniques to prevent unwanted cell proliferation at certain locations in the eye, such as at the retina or at the lens capsule. For example, because the retina is very sensitive, known radiation techniques can be too severe to treat cancerous cells on, in or under the retina.

Also, after cataract surgery, a phenomenon known as capsular opacification and, in particular, posterior capsular opacification can occur in which the epithelial cells on the lens capsule of the eye experience proliferated growth. This growth can result in the cells covering all or a substantial portion of the front and rear surfaces of the lens capsule, which can cause the lens capsule to become cloudy and thus adversely affect the patient's vision. These cells can be removed by known techniques, such as by scraping away the epithelial cells. However, it is often difficult to remove all of the unwanted cells. Hence, after time, the unwanted cells typically will grow back, thus requiring further surgery.

Accordingly, a need exists for a system and method for preventing unwanted cell proliferation at sites in the body, especially at sites in the eye such as the retina and lens capsule, which does not suffer from the drawbacks associated with the known techniques discussed above.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a system and method for preventing the proliferation of unwanted cells at various sites in the body, especially at sites in the eye such as the choroid, retina and lens capsule.

Another object of the invention is to provide a system and method for thermally and chemically treating cells at sites in the body to kill the cells or impede cell multiplication without causing protein denaturation to occur in the cells.

A further object of the present invention is to provide a system and method which uses an energy emitting device to heat cells at a site of interest in the body to a temperature which kills the cells without causing protein denaturation in the cells, and which also chemically treats the cells, if desired, to change a physical characteristic of the cells to thus cause cell death or impede cell multiplication.

These and other objects of the invention are substantially achieved by providing a system and method for treating cells of a site in the body, such as at a lens capsule or choroid of an eye. The system and method employs an energy emitting device, and a positioning device, adapted to position the energy emitting device at a position in relation to the cells at the site in the body, such as the cells of the lens capsule or choroid, such that energy emitted from the energy emitting device heats the cells to a temperature which is above body temperature and below a temperature at which protein denaturation occurs in the cells, to kill the cells or impede multiplication of the cells. The energy emitting device can include a container containing a heated fluid which heats the cells to the desired temperature, a portion of the heated fluid being indocyanine green.

The system and method can further employ a material delivery device that can be unitary with or separate from the energy emitting device, an can provide a material, such as indocyanine green, to the cells at the site of interest. A light emitting device can be controlled to direct light onto the site of interest to activate the indocyanine green present at the cells to alter a physical characteristic of the cells.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1is a cross-sectional view of an eye100into which is being inserted a device102for treating cells according to an embodiment of the present invention. As shown, the eye100includes a cornea104, an iris106, and a lens108having a lens capsule110. In this example, the device102is being used to treat epithelial cells of the lens108that has undergone or is undergoing a cataract procedure.

As discussed in the Background section above, it is known in the art that after cataract surgery has been performed on a lens of an eye, the epithelial cells of the lens can proliferate on the front and rear surfaces of the lens capsule. This cell proliferation is known as capsular opacification, which causes the lens capsule to become cloudy and thus adversely affect vision. As will now be described, the device102can be used to treat the epithelial cells of the lens to kill or impede cell growth, and thus prevent or minimize capsular opacification. Specifically, the device102can be used to apply a hyperthermia treatment (heating) to the cells to kill the cells or impede cell growth.

As mentioned in the Background section above, when cells are heated to a temperature of about 5° C. or more above the normal body temperature of 37° C., cell death begins to occur. Specifically, heating cells to a temperature between about 42° C. and about 50° C. causes cell death. Heating cells to higher temperatures, such as about 60° C. and above, causes protein denaturation to occur in the cells, which results in immediate cell death. The protein denaturation phenomenon also causes coagulation of the cells in the heated area.

It is also known that cells can tolerate certain drugs or chemicals at normal body temperature or slightly above normal body temperature. However, as the temperature of the cells is increased to, for example, about 42° C. or above, drugs that are normally tolerated by the cells at normal temperature can have a deleterious effect on the cells at these higher temperatures. The device102uses the effect of temperature and, if desired, chemicals to treat the cells of the lens capsule110to prevent or impede cell proliferation.

As shown inFIGS. 2 and 3, device102includes a shaft portion112and an expandable portion114. The device102can be made of a synthetic material such as silicone, plastic or any other suitable material. The shaft portion112includes a wall portion116and a chamber118. The wall portion116can include an insulating material, or can have a thickness sufficient to insulate the chamber118from the environment outside the shaft portion112. Also, the wall portion116can include a chamber that is filled, for example, with air which acts as a insulator.

As further illustrated, the shaft portion112in this example is integral with the expandable portion114. However, the device102can be configured so that the shaft portion112is attachable to the expandable portion114. Expandable portion114has a wall portion120that can be made of the same material as shaft portion112, or any other suitable expandable material. The wall portion120defines a chamber122that is in communication with chamber118of shaft portion112. The wall portion120can be porous to allow liquid to pass therethrough, or can have one or more openings124therein, if desired, to allow fluid collected in chamber122to pass therethrough. However, the wall portion120can also be impermeable to fluid, if desired.

In the example shown inFIG. 1, the device102is used to treat the cells and, in particular, the epithelial cells on the anterior and posterior surfaces of the lens capsule110on which cataract surgery is being or has been performed. As can be appreciated by one skilled in the art, to perform cataract surgery, a small incision is made in the cornea104of the eye100, and a small incision is made in the lens capsule110. The cortex and nucleus of the lens108is removed through the small opening in the lens capsule110.

The expandable portion114of the device102, along with some of the shaft portion112, if necessary, is inserted into the small incision in the lens capsule110. A heated fluid such as water or saline solution or any other suitable solution is provided into the chamber118of the shaft portion112, and flows into the chamber122of the expandable portion114. The liquid also can be viscous or semiviscous, if desired.

In one example, the fluid has been heated to a temperature of about 40° C. to about 100° C. and, preferably, between about 42° C. to about 60° C. A device (not shown) controls the temperature of the fluid to maintain the temperature within the desired range. The device also controls the pressure at which the fluid is provided into the chamber122to expand the expandable portion114in a balloon-like manner by a desired amount. Furthermore, a timing device can be used to monitor the time during which the expandable portion114should remain in contact with the cells, which can be within a range of about 1 minute or about 10 minutes, or any suitable period of time to achieve the desired results.

Accordingly, the temperature of the liquid in the chamber122of the expandable portion114heats the cells surrounding and in proximity to the expanded expandable portion122to a desired temperature within a range of about 45° C. to about 50° C. Although the cells heated to this temperature will die, the cells will not experience protein denaturation. Therefore, these cells will not coagulate and will not cloud the lens capsule110. The time during which the expandable portion114having the heated solution therein is maintained in contact with the cells also is closely monitored to assure that underheating or overheating does not occur.

The expandable portion114can be placed inside the anterior of the lens capsule110, the posterior of the lens capsule110, or at the outside anterior and posterior surfaces of the lens capsule110instead of inside the lens capsule to kill the epithelia cells. It can be also noted that the expandable portion114of the device102can be inserted into the lens capsule110, or can be placed on the outside surfaces of the lens capsule110, before the cortex, the nucleus, or both, have been removed.

It is further noted that a drug or material can be included in the heated fluid114when the heated fluid is being provided into chamber116and thus into chamber122, or can be added to the fluid in the chamber122via chamber116at an appropriate time. The drug or material can be of the type that can be tolerated by cells under normal temperature, but which can enhance cell death at the elevated temperature. These drugs or chemicals can be antiproliferative or anticancer drugs, antibiotics which act on cell membranes or internal structures of the cells, agents which act as surfactants, or agents which contain alcohol at various concentrations. Also, the chemicals can be photosensitizers for reasons described in more detail below. These chemicals and drugs can pass through the porous membrane of the wall120of expandable portion114, or through the openings in expandable portion114, to come in contact with and be absorbed by the cells. Alternatively, if a device102having a non-porous expandable portion114or an expandable portion114having no openings therein is used to heat the cells, that device can be removed and replaced with another device102having a porous expandable portion114or an expandable portion114having openings therein, so that the drugs or chemicals can be delivered to the cells through this second device.

After the expandable portion114has been kept in contact with the cells for the appropriate length of time, the expandable portion114can be deflated and removed from the lens capsule110. Alternatively, instead of removing the expandable portion114right away, the expandable portion114can be allowed to remain deflated in the lens capsule110for a desired period of time, and then reexpanded to repeat the heating process and/or the drug or chemical delivery process described above. Once the treatments have been completed, the expandable portion114can be deflated and removed from the lens capsule110. An artificial lens can then be implanted inside the lens capsule110.

It is noted that the device102need not be configured as shown in FIG.2. Rather, as shown inFIG. 4, the device can be configured as a device126having a shaft portion128and an expandable portion130at a position along the shaft portion128as illustrated. The device can alternatively be configured as device132as shown inFIG. 5, having a shaft portion134and round or substantially round expandable portion136. The device can alternatively be configured as device138as shown inFIG. 6, having a shaft portion140and a disc-shaped expandable portion142. Also, the device can be configured as device144as shown inFIG. 7, having a shaft portion146and extended expandable portion148. Furthermore, the device can be configured as device150as shown inFIG. 8, having a shaft portion152and two or more expandable portions154.

It is further noted that the devices shown inFIGS. 4 through 8can be made of the same or substantially the same materials as device102shown inFIG. 2, and can function in substantially the same manner as device102. The expandable portions of all the devices shown in FIGS.2and4-8can be porous or include openings as described above, or be non-porous and include no openings. Furthermore, the expandable portions of all the devices shown inFIGS. 2 and 4through8can be configured as expandable portion156shown inFIG. 9, which includes ridges or abrasive portions158on its exterior. These ridges or abrasive portions can be used to remove dead cells from the site of interest if the device is moved so that its expandable portion rubs against the site of interest.

As shown inFIG. 10, the device can be configured as a device160having a shaft portion162and an expandable portion164. The expandable portion164in device160is similar to the expandable portions of all the device shown inFIGS. 2 and 4through8as discussed above. However, as illustrated, the expandable portion164is at a distance from the distal end166of the shaft portion162.

Furthermore, the shaft portion162includes an inner shaft168defining a chamber170, and an outer shaft172which defines a chamber174between its inner wall and the outer wall of shaft168. The shaft portion162and expandable portion164can be made of the same or substantially the same materials as the shaft portion and expandable portions of the devices discussed above. However, in this example, the chamber of shaft portion168does not communicate with the interior chamber of expandable portion164. Rather, the chamber170defined by shaft168can pass through the shaft portion162to therefore allow fluid to pass through shaft portion162to the site of interest, or to allow fluid to be aspirated from the site of interest through chamber170. Alternatively, the distal end of the shaft portion162can be closed. The chamber174, on the other hand, can be used to introduce fluid into the chamber176of the expandable portion164. This fluid can be heated fluid as discussed above with regard to device102to heat the cells at the site of interest to kill the cells or impede cell multiplication without causing protein denaturation. The drugs or chemicals described above can also be added to the fluid for the purposes described above.

As shown inFIG. 11, the device can be configured as device178having a shaft portion180and an expandable portion182which can be similar to the shaft portion112and expandable portion114of device102. However, device178can also include a first tube182defining a chamber186therethrough, and a second tube188defining a chamber190therethrough. As can be appreciated by one skilled in the art, tubes184and188can be used to irrigate and aspirate the site of interest that is being treated by the expandable portion182. That is, a fluid, such as water or a saline solution, can be ejected from chamber186of tube184to the site of interest, and then aspirated through chamber190of tube188. These irrigation and aspiration operations can remove cells which were killed by the heating process performed by expandable portion182, which is similar to the heating process performed by expandable portion114of device102as discussed above.

As shown inFIG. 12, the device can be configured as device192which is similar to device102. Device192includes a shaft portion194and an expandable portion196, which are similar in construction to shaft portion112and expandable portion114of device102. That is, shaft194defines a chamber198therein, and expandable portion196defines a chamber200therein. Heated fluid can be applied to chamber200via chamber198to expand expandable portion196in a manner similar to that described above with regard to device102.

However, device192can further include a probe202that is inserted into chambers198and200as shown. The probe can be a metal heating probe, a fiber optic probe or any other suitable probe for delivering energy to the fluid in chamber200. Specifically, as shown inFIG. 12, the probe202has a tip204from which energy such as thermoenergy, radiation, ultrasonic waves, microwaves, ultraviolet light waves, infrared light waves, or any other suitable energy can be emitted. Accordingly, the energy emitted from the tip204of probe202can heat the fluid contained in chamber200, to thus thermally treat the cells at the site of interest in a manner similar to that described above with regard to device102.

In addition, as mentioned above, a photosensitive material can be added to the fluid provided to chamber200to chemically treat the cells at the site of interest. The photosensitizers preferably are indocyanine green, but can be, for example, aminolevulinic acid, porphyrin derivatives, purine derivatives, NPE6, ATX-10, plant-derived photosensitizers, or other synthetic sensitizers such as SNET2, Lutex, and the like. The concentration of the photosensitizers in the fluid should be at non-toxic levels.

Similar to expandable portion114discussed above, expandable portion196can be porous or can include openings therein to allow the fluid contained in chamber200to pass there through and contact or be absorbed by the cells at the site of interest. Accordingly, the photosensitizers contained in the fluid in chamber200can pass through the porous walls of expandable portion196, or through openings in expandable portion196, to come in contact with the cells at the site of interest, and be absorbed by the cells.

Assuming that the probe202is a fiber optic, light having a wavelength that will activate the photosensitizers contained in the fluid can be propagated through probe202and be admitted at the tip204of the probe. This light can be laser light, light generated by a LED, white light, or any other light of a wavelength that will activate the photosensitizers in the fluid. The activated photosensitizers that are in contact with or have been absorbed by the cells at the site of interest can alternate physically characteristic of those cells or, in other words, cause damage to those cells. Accordingly, in the example described above with regard toFIG. 1, the epithelial cells of the lens capsule110(seeFIG. 1) can be damaged by the activated photosensitizers. This damage caused by the activated photosensitizers can kill the cells which have not been killed by the heating process, or can further damage the cells that have been damaged by the heating process to impede cell growth.

It is also noted that all the different configurations of the device as shown inFIGS. 4-11can similarly include a probe202for purposes described above. For example, as shown inFIG. 13, the device160can include probe202in chamber174so that the tip204of the probe202extends into the chamber1176of the expandable portion164. The probe202can be used as described above to heat the fluid, energize photosensitive materials contained of the fluid, or both.

It is also noted that the devices shown in FIGS.2and4-13as described above can be used to treat cells at locations in the body other than the lens capsule. For example, the devices can be used to treat cells in blood vessels, skin and mucus tissues, the intestine, vagina, uterus, bladder, urethra, prostate, rectum, sinuses, brain, breast, heart, or any site in the body. The manner in which the devices are used to treat cells at these various locations in the body is similar to that described above with regard to the treatment of cells at the lens capsule.

That is, the device, such as device102, is positioned so that the expandable portion114is in contact with or proximate to the cells to be treated. The heated fluid is then provided into the chamber122of expandable portion114in a manner described above to thermally treat the cells, and thus kill the cells without causing protein denaturation. The expandable portion114can be porous or can include openings as described above from which the fluid inside the chamber122can pass. As further described above, the fluid can include a photosensitizer which can come in contact with or be absorbed by the cells when the fluid passes through the pores or openings in the expandable portion114. A probe202as shown, for example inFIG. 12, can be used to emits light of an appropriate wavelength to the cells of interest so that the photosensitizers in contact with or absorbed by the cells of interest are activated by the light, and thus change a physical characteristic of the cells or damage the cells as described above.

It is further noted that multiple devices can be used to perform the heating and photosensitizing process period. That is, a device such as device102can include an expandable portion114that is not porous or has no openings therein, and can be used in a manner similar to that described above to heat the cells at the site of interest to kill the cells without causing protein denaturation. That device can then be removed, and a second device having an expandable portion114that is permeable or has openings therein can be used to deliver the photosensitizer to the cells at the site of interest. This second device102can further include a probe202as described above which can be controlled to emit light which will activate the photosensitizers and thus cause the photosensitizer which have been absorbed by the cells or in contact with the cells to change the physical characteristic of the cells. The probe202could also be used to heat the fluid in the expandable portion114in the manner described above.

It is further noted that the devices as shown in FIGS.2and4-13as described above can be used to deliver other chemicals, such as antiproliferative drugs or anticancer chemicals, to the cells of the site of interest through openings or pores in their expandable portions. Furthermore, it is noted that the heating of the site of interest also expands the capillaries and vasculature at the site of interest, thus allowing more blood to flow to the site of interest. Accordingly, the photosensitizers or other drugs such as antiproliferative or anticancer chemical can be delivered systemically or, in other words, intravenously to the body. Because the drugs or chemicals are flowing through the body's blood stream, the drugs or chemicals will reach the site of interest through the expanded capillaries and vasculature. If the drugs or chemicals are photosensitizers, the device102or any of the other devices shown inFIGS. 4-13can still be used to activate the photosensitizers at the site of interest.

That is, any of those devices can include a fiber optic probe202which can be used to emit light having a wavelength that activates the photosensitizers at the site of interest. The activated photosensitizers will then alter a physical characteristic of the cells at the site of interest as described above. It is noted that photosensitizers such as benzoporphynines can be activated with light having a wavelength between about 680 nm to about 695 nm, while NPE6 is activated by light having a wavelength between about 660 nm and about 670 nm. Lutex, on the other hand, is activated with light having a wavelength of about 725 nm, and SNET2is activated with light having a wavelength of about 660 nm to about 670 nm. It is further noted that the photosensitizers as well as the antiproliferative or anticancer chemicals can be delivered systemically to the site of interest or applied directly to the site of interest via any of the devices shown in FIGS.2and4-13as described above before, during, or immediately after the cells have been thermally treated to enhance the killing effect on the cells.

AlthoughFIGS. 1-13and the above disclosure describe a device having an expandable portion for treating cells at the site of interest, other types of devices can be used to provide the same or similar treatment. For example, as shown inFIG. 14, a system206can include a plurality of light emitting devices208and210which can be, for example, lasers, LED's or any other type of light-emitting devices known in the art. Light-emitting device208emits light to a mirror arrangement212, for example, which includes mirrors214,216and218. Accordingly, light being emitted by light-emitting device208is reflected by mirrors214and218, and can be directed toward an eye220such that the lightwaves pass through the cornea222and are focused by the lens224onto a desired site on the retina226. Similarly, the light being emitted by light emitting device210is reflected by mirror216and mirror218to enter the eye220and be focused by lens224on the desired site on retina226.

In the system shown inFIG. 14, one of the light-emitting devices, for example, light-emitting device208, can emit light such as laser light, infrared light, ultraviolet light, or any other suitable type of light, having a wavelength and intensity which will feed the cells on, in or under the portion of the retina226onto which the light propagates. The light-emitting device208can be controlled so that the intensity of the light will only heat the cells to a temperature below, for example, 60° C., to cause cell death without causing protein denaturation and thus, coagulation of the cells. Preferably, the cells are heated to a temperature within the range of about 42° C. to about 50° C. The cells also are exposed to the light for an appropriate amount of time, such as 1 to 10 minutes, as necessary, to effectively kill the cells without overheating the cells to cause protein denaturation to occur. It is further noted that the light-emitting device208could alternatively be a microwave emitting device, ultrasonic emitting device, radiation emitting device, or any other suitable energy emitting device as described above which will sufficiently heat the cells to thermally treat the cells as described above.

Before, during or after the light-emitting device208is controlled to heat the cells in the manner described above, a photosensitizer of the type as described above can be delivered to the site of interest at the retina226either locally through the use of a device such as that shown in FIGS.2and4-13, or systemically through the patient's blood stream as described above. Once the cells have been thermally treated by the light being emitted from light-emitting device208, light-emitting device210can be controlled to emit light having a wavelength which will activate the photosensitizer that have been absorbed by or are in contact with the cells at the site of interest on the retina226. In one example, the light emitted by light-emitting device208to heat the cells can have a wavelength between about 700 nm to about 1200 nm. However, the light emitted by the light-emitting210should have a wavelength which activate the photosensitizer used. For example, if NPE6 is used, the wavelength of the light should be about 664 nm.

It should be also understood that the light being emitted by light-emitting device210can be emitted before, during or after the heat-treating process. It is further noted that the heat-treating process could be performed using a device as shown, for example, in FIGS.2and4-13, while the photosensitizers can be activated using a light-emitting device, such as light-emitting device210as described above. It is further noted that the system206described above for delivering different types of light to a site of interest in a body can be modified in several ways. For example, as shown inFIG. 15, the system206can be configured to include a fiber optic device228, which can be a flexible fiber optic cable or probe, or any other suitable type of fiber optic device that can receive the light being emitted by light-emitting devices208and210. The distal end230of the fiber optic device228can then be aimed to the site of interest in a body, for example, at a site of interest on the retina226(see FIG.14), or at any other site of interest in the body. The fiber optic probe228can also be inserted into the body so that the tip230can be placed proximate to the site of interest.

As further shown inFIG. 16, the light-emitting devices208and210can instead be attached to a fiber optic probe232having a first fiber optic cable234and a second fiber optic cable236. The tip238of the fiber optic probe can be aimed toward or placed proximate to a site of interest240in a body, such as at a site of interest on the retina226(seeFIG. 14) or at any other site in a body, so that the light emitted by light-emitting devices208and210can radiate onto the site of interest to treat the cells in a manner described. As shown inFIG. 17, a converging lens240can be used in conjunction with either light-emitting sources208or210to converge the light being emitted by either of those light sources to a point, so that the light can be focused more precisely on a site of interest, or be received more efficiently into a fiber optic probe, such as fiber optic probe228in FIG.15. Also, as shown inFIG. 18, a diverging lens242can be used with either of the light-emitting devices208or210to diverge the light rays being emitted by those light-emitting devices so that the light waves can cover a larger area of the site of interest.

In addition, as shown inFIG. 19, light-emitting devices208and210can be coupled to a fiber optic device244having fiber optic cables246,248250and252. In this example, light-emitting device208is coupled to fiber optic cable246, and light-emitting210is coupled to fiber optic cable248. Accordingly, the light being emitted by light-emitting devices208and210is emitted from the tip254of the fiber optic probe244to propagate onto the site of interest to treat the cells at the site of interest in the manner described above.

Furthermore, fiber optic cable250can be coupled to an illumination source256which can provide light which passes out of the tip254of fiber optic probe244to illuminate the site of interest. Furthermore, fiber optic cable252can be coupled to a monitor258, such a television monitor, fluoroscope, CT-scan, or any other similar device, which can be used to monitor the site of interest that is being illuminated by the light emitted from illumination device256and is being treated by the light emitted by light-emitting devices208and210.

It is further noted that the devices described above with regard to FIGS.2and4-13can be modified in other ways to better suit the application in which they are being used. For example, as shown inFIGS. 20 and 21, a device260having a shaft portion262and expandable portion264similar to shaft portion112and expandable portion114described above can be used to treat cells at a site of interest within, for example, a patient's vasculature266. In order to allow blood to flow more freely through the device260, the shaft262can be configured with openings268therein, which will allow blood to freely flow through the chamber270defined by shaft portion262.

As shown inFIG. 21specifically, a tube272can be in communication with the chamber274of expandable portion264to provide a heated fluid to the chamber274to thus expand the chamber264and heat the cells at the site of interest in a manner similar to that described above with regard to, for example, device102. It is note that the chamber270does not communicate with chamber274in this example. Furthermore, the device260can also include a probe202similar to that described above which can emit energy, such as light energy, microwave energy, ultrasonic energy, or any other suitable energy at its tip204to activate photosensitizers that have been delivered to the cells at the site of interest by the fluid leaking through the pores or openings in expandable portion264, or systemically through the patient's blood stream. The energy can also be used to heat the fluid in the chamber274.

Furthermore, indocyanine green (ICG) can be placed in the eye to alter cells therein. ICG is an agent that is known in the art and has been used in ophthalmology and cardiology for angiography of the back of the eye and for cardiac function, respectively. Specifically, ICG has been used on to enhance coagulation of portions of the eye. ICG absorbs a wavelength of between about 800 nm and about 810 nm and has a fluorescence of between about 820 nm and about 830 nm. To activate ICG, a fluorescent light passes through a filter and activates the fluid in which the ICG has been dissolved or applied. The image is then captured by an image intensifier for ICG angiography. For a further discussion of ICG, see U.S. Pat. No. 2,895,955, which is incorporated herein by reference.

However, using the above described methods, ICG can be used in conjunction with Transpupillary Thermotherpy (TTT or hyperthermia). At an increased concentration, ICG lowers the threshold for the damage to the choroid209(see FIG.14). It has been determined that ICG creates a difference in the threshold at which damage occurs in choroidal vessels and retinal vessels during TTT treatment. The choroidal vessels can be closed or altered quicker or at lower power levels than the retinal vessels and therefore, treatment of choroidal neovascularization in age related macular degeneration is possible, while simultaneously protecting the retinal vessels. For examples of the threshold power levels for the choroidal vessels for pigmented and non-pigmented rabbits, and the change in the threshold power levels for the choroidal vessels with the addition of ICG, are shown in the following charts:

TTT Thresholds for Pigmented Rabbits

As shown specifically in the above chart, as the concentration of ICG is increased from 0 to 1.4 mg/kg of body weight of the subject, the power required to damage the choroidal vessels decreases from 1500 mW to 750 mW, while the power to alter or close the retinal vessels remains substantial the same for the varying concentrations of the ICG. However, as noted above the subjects in the chart are pigmented and non-pigmented rabbits. The amount of power required to damage the choroidal vessels in a human patient varies according to the pigmentation, the time the power is applied and size (diameter) of the spot. For example, the power to damage the choroidal vessels in a human for a non pigmented spot of about 3 nm in diameter is about 1500 mW or less for 60 seconds. It would be necessary to alter the time and/or power of the application of the light emitting device depending on the particular size and pigmentation of the spot.

ICG is preferably injected intravenously in the amount of between about 1 mg/kg to about 15 mg/kg of a patient's body weight, and more preferably, in the amount of about 1 mg/kg to about 3 mg/kg. In another embodiment, a fluid containing ICG is introduced to the patient in an amount to provide about 0.4 mg/kg to about 1.4 mg/kg based on the patient's body weight. As seen inFIG. 14, a laser diode208and/or210, or any other light emitting device, is then aimed and energized at a predetermined level of power, preferably between about 1500 mW or less to activate the ICG and the desired area of the eye. However, the light emitting device can be energized at any desired power that would achieve the desired result. Since ICG is a fluorescent dye, it can be used for simultaneously seeing and treating the cells. The ICG will then alter a physical characteristic of the cells at the site of interest, as described above, to kill or impede multiplication of the choroid cells. Preferably, the ICG will alter the choroidal cells, like a photsensitzer, thus treating the choroidal neovascularization while not altering the retinal cells.

Additionally, ICG can be used to damage the lens epithelium, by injecting ICG into the lens capsule and using laser light of about 800 nm to about 810 nm. As seen inFIG. 1, preferably, device102is used to apply a fluid or material containing ICG. The device is inserted into the eye and applies the fluid or material to the lens capsule110of eye100, similar to the application of the material described above. The concentration of ICG is preferably about 1-200 micograms per milliliter of fluid, with the fluid preferably being saline solution. However, the fluid may be any type of fluid that would not adversely affect the eye, when applied to the eye, and the concentration of ICG can be any concentration that would achieve the desired results. Once the material or fluid is applied, the ICG can be activated using a diode laser or any other light emitting device that is preferably directed to the ICG by optical fiber, as described above. The light emitting device can either be attached to device102or can be separate. Additionally, if desired, the light emitting device can activate the ICG from a position that is outside of the eye100, as described above. The fluid having a concentration of ICG may be used in any of the above described application devices and is not limited to device102.

The ICG not only absorbs the light from the light emitting device, but also has some photosensitizing capabilities, which can thus damage the lens cell membrane when exposed to light having the above described wavelengths. This damage, however, is different than photocoagulation where protein denaturation occurs. By using ICG, most of the damage to the cell membrane occurs above the body temperature and below the temperature of 60 degrees Celsius, which is the temperature at which protein denaturization typically occurs. Heating the cells at this temperature range thus minimizes the coagulative effect on the surrounding tissues.

It is also noted that the cells can be irradiated with radiation before, during or after being treated thermally in the manners described above. The radiation can be delivered by the same device, such as device102, that is used to heat the cells to perform the hyperthermia treatment as described above. Specifically, the shaft portion of the device can be covered with or otherwise include a protective shield that prevents radiation from escaping the device. The expandable portion allows radiation to be emitted therefrom, although a portion of the expandable portion of the device can also include a protective shield.

The radiation used to treat the cells can be either beta radiation with a very short span, such as radiation emitted by strontium or iridium. However, gamma radiation such as that emitted by P32, Iodine 95, Palladium 90, or so on, can also be used. The other isotopes used in the solution can be tritiated (radioactive hydrogen), radioactive carbon, and so on. The components described above which emit the radiation can be made into small particles which are included in the fluid that is delivered into the expandable portion of the device as described above. Accordingly, the fluid will heat the cells of interest to kill the cells or impede cell growth, and the radiation will further enhance the cell killing effect. The hyperthermia technique of heating the cells can also be performed prior to irradiating the cells with radiation. In this event, separate devices can be used to heat the cells and irradiate the cells. It is also noted that the photosensitizer techniques described above can also be performed. Furthermore, antiproliferative drugs or anticancer drugs can also be applied to the cells at the site of interest.

It is also noted that this technique of using the device to treat cells with radiation as described above can be used to treat cells at any suitable site in the body. More particularly, it can be noted that when treating cells of the lens capsule, such as epithelial cells as described above, it is not necessary to heat the cells if the radiation technique is used. Rather, radiation alone can be applied to the cells of the lens capsule by the device, such as those described above, to kill the cells or impede cell growth. However, it can be also be advantageous to treat the cells of the lens capsule with heat and radiation, a well as with photosensitizers, antiproliferative and anticancer drugs.