Patent Publication Number: US-8535360-B2

Title: Systems and methods for treating superficial venous malformations like spider veins

Description:
RELATED APPLICATION 
     This is a continuation patent application of U.S. patent application Ser. No. 11/446,800, filed 5 Jun. 2006 now U.S. Pat. No. 7,465,312, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/796,656, filed 2 May 2006, and entitled “Systems and Methods for Treating Superficial Venous Malformations Like Spider Veins,” which is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     As the large group of so-called baby-boomers advances in age, there are increasing demands for effective, non-invasive treatment of vascular diseases or dysfunctions affecting the vascular system. There are also increasing demands for non-invasive cosmetic surgery to repair conditions that have vascular origins. 
     For example, spider veins result from various dysfunctions in the veins. Veins carry oxygen-poor blood from the body back to the heart. 
     Spider veins can be caused by the backup of blood, when one-way flap valves in veins become weak, causing blood to collect in veins. Spider veins can also arise due to other causes, e.g., hormone changes, inherited factors, and exposure to the sun. Spider veins are often red or blue and close to the surface of the skin. They can look like tree branches or spider webs with their short jagged lines. Spider veins can be found on the legs and face. They can cover either a very small or very large area of skin. 
     Sclerotherapy is a common treatment for spider veins. Sclerotherapy involves the injection of a solution into the vein that causes the vein walls to swell, stick together, and seal shut. This stops the flow of blood and the vein turns into scar tissue. Microsclerotherapy uses special solutions and injection techniques that can increase the success rate for removal of smaller spider veins. Sclerotherapy involves tedious, hard to learn injection techniques. It can lead to side effects like stinging or painful cramps where the injection was made, or temporary red raised patches of skin, or skin sores, or bruises. The treated vein can also become inflamed or develop lumps of clotted blood. Applying heat and taking aspirin or antibiotics can relieve inflammation. Lumps of coagulated blood can be drained. 
     Laser surgery can be used to treat larger spider veins in the legs. Laser surgery sends very strong bursts of light onto the vein, which makes the vein slowly fade and disappear. Laser surgery is more appealing to some patients because it does not use needles or incisions. Still, when the laser hits the skin, the patient can feel a heat sensation that can be quite painful. Laser surgery can cause redness or swelling of the skin, and can cause burns and scars. Depending on the severity of the veins, two to five treatments (15 to 20 minutes each) are generally needed to remove spider veins in the legs. Moreover, for spider veins larger than 3 mm, laser therapy is not very practical. Furthermore, the capital cost for purchasing trans-dermal lasers can be quite high, making the treatment relatively costly. 
     There is need for devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical and/or cosmetic surgical treatment of superficial venous malformations, such as e.g., in the treatment of spider veins. There is also a need for devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly treatment of diseases or dysfunctions in any region of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye. 
     SUMMARY OF THE INVENTION 
     The invention provides devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical and/or cosmetic surgical treatment of superficial venous malformations, e.g., spider veins. 
     The invention also provides devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical treatment of diseases or dysfunctions in regions of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye. 
     According to one aspect of the invention, the devices, systems, and methods distribute a light-reactive agent at, in, or near an inner wall of a vein. The devices, systems, and methods activate the light-reactive agent by applying light energy at a wavelength that activates the light-reactive agent to cause localize injury to the inner wall of the vein. The light energy is desirably non-thermal and is generated by a low voltage photoactivation device, comprising, e.g., one or more light-emitting diodes. In one embodiment, the light-reactive agent comprises verteporfin that is administered intravenously. Devices, systems, and methods that incorporate this aspect of the invention can treat superficial venous disease, like spider veins. 
     The devices, systems, and methods improve the quality of patient care. The devices, systems, and methods eliminate side effects such as brusing, burning, and skin discoloration. The devices, systems, and methods do not require tedious, hard to learn injection techniques. They do not require high cost trans-dermal lasers. The devices, systems, and method are usable by a large group of practitioners, such as dermatologists, phlebologists, vascular surgeons, and interventional radiologists. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a system of devices for treating a superficial venous disease, such as spider veins using a light-reactive agent, the agent being suited for intravenous injection. 
         FIG. 2  is a perspective view of the system shown in  FIG. 1  packaged as a kit, with directions for using the devices to treat a superficial venous disease. 
         FIGS. 3A and 3B  are side section views, taken generally alone line  3 - 3  in  FIG. 1 , showing alternative embodiments of the internal components of a photoactivation device that forms a part of the system shown in  FIG. 1 . 
         FIGS. 4 to 14  show a representative method of using a system like that shown in  FIG. 1  to treat spider veins. 
         FIG. 15  shows an alternative embodiment of a source of a light-reactive agent usable with the system shown in  FIG. 1 , the agent being in tablet or capsule form, for oral ingestion. 
         FIG. 16  shows an alternative embodiment of a source of a light-reactive agent usable with the system shown in  FIG. 1 , the agent being in cream form for topical application. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims. 
       FIG. 1  shows devices that together comprise a system  10  for treating a vascular disease or a dysfunction affecting the vascular system using light-reactive agents. The devices and system  10 , and their associated methods of use, are particularly well suited for treating superficial venous diseases, such as spider veins. For this reason, the devices and system  10 , and their associated methods of use will be described in this context. 
     Still, it should be appreciated that the disclosed devices and system  10 , and their associated methods of use are applicable for use in treating other diseases or dysfunctions elsewhere in the body that are not necessarily related to spider veins or their cause, but are nevertheless capable of treatment by light-reactive agents carried by blood. Other conditions that can be treated by light reactive agents using the system  10  or a form of the system  10  include cancer, e.g., breast or prostrate cancer; conditions of the ear, nose, or throat; periodontal disease; and conditions of the eye or sight (opthalmology). 
     As  FIG. 1  shows, the system  10  includes at least one source  12  of a selected light reactive agent  14 . The source  12  can be provided in various forms. For example, as shown in  FIG. 1 , the source  12  can comprise a conventional vial  16  containing the light reactive agent  14  in solution suited for intravenous injection. Alternatively, the source  12  can comprise the light reactive agent  14  packaged with a carrier in tablet or capsule form for oral ingestion; or incorporated into a cream that can be applied topically to the skin. 
     The light reactive agent  14  can comprise any light-reactive drug suited for photodynamic therapy (PDT). PDT is a treatment that uses an agent or drug, also called a photosensitizer or photosensitizing agent, and light energy of a particular selected wavelength. The photosensitizers, which are inert by themselves, bind to proteins found in blood, e.g., lipoproteins. The proteins act as carriers, transporting the photosensitizers to cells targeted for treatment. When exposed to light of the particular wavelength (which varies according to the photosensitizer), the photosensitizer reacts with oxygen. The reaction transforms the oxygen into singlet oxygen and free radicals. The singlet oxygen and free radicals disrupt normal cellular functions and cause cell death. 
     The light reactive agent  14  can be selected among a group of photosensitizers, depending upon type and location of tissue being treated, as well as the mode contemplated for its introduction into body tissue. Each photosensitizer is activated by light of a specific wavelength. This wavelength determines how far the light can travel into the body. Thus, the physician can select a specific photosensitizer and wavelength(s) of light to treat different areas of the body. 
     In use, whatever the form, the selected light reactive agent  14  is administered by the system  10  for delivery to a targeted tissue treatment site at, in, or near an inner wall of a vein. In the context of the illustrated embodiment, the targeted tissue site is a sub-dermal region where one or more spider veins are present (this is shown  FIG. 4  and will be described in greater detail later). 
     The form for administration will depend upon the form of the source  12 . The light reactive agent  14  can be provided in tablet or capsule form  54  (see  FIG. 15 ), which can be ingested orally for absorption by the GI tract for systemic distribution by blood to the targeted tissue treatment site. The light reactive agent  14  can be incorporated into a cream form  56  (see  FIG. 16 ), and the light reactive agent  14  can be applied topically for percutaneous absorption by the skin to the targeted tissue treatment site. 
     It has been discovered that an injectable form of the porphyrin-based photosensitizer called verteporfin—commercially available from QLT, Inc. as VISUDYNE® material (verteporfin for injection)—can be intravenously administered to effectively treat spider veins using the system  10  shown in  FIG. 1 . Therefore,  FIG. 1  shows the light reactive agent  14  in solution in the vial  16 . 
     VISUDYNE® material has been used, together with a special laser light, to treat abnormal blood vessel formation in the eye, called age-related macular degeneration (AMD) (which, if untreated, can lead to loss of eyesight). VISUDYNE® material can be activated by shining a pre-calculated dose of light at a particular (wavelength 689 nm) by a low-energy laser or light source  12  into the affected area of tissue. 
     In the context of the illustrated embodiment, where the source  12  comprises an injectable solution of the light reactive agent  14 , the device takes the form of a conventional hand-held syringe  18 . The syringe  18  draws the light reactive agent  14  in solution from the vial  16  (as shown in  FIG. 6 ) and injects the photodynamic material in solution into the vascular system for transport by the blood flow to the targeted tissue site (as shown in  FIG. 7 ). Instead of a handheld syringe  18 , the administration device can take the form of a conventional intravenous (IV) delivery catheter or set coupled to a syringe or other intravenous delivery device or pump. 
     As  FIG. 1  also shows, the system  10  includes a photoactivation device  20 . The photoactivation device  20  includes one or more light sources  22  (see  FIG. 3 ). The light sources  22  have a wavelength or a range of wavelengths. The photoactivation device  20  also includes means for controlling the intensity or a range of intensities, spot size or a range of spot sizes, and other operating characteristics of the light sources  22  that are conducive to activation the light reactive agent  14  in a desired manner. Desirably, the photoactivation device  20  comprises non-thermal light energy generated by a low-voltage source (not greater than 12 Volts). 
     The photoactivation device  20  can take various forms, depending upon nature, location, and size of the targeted tissue region. The photoactivation device  20  can, e.g., be mounted on an adjustable frame that is located above or below the targeted tissue region of an individual. The photoactive device may, alternatively, deliver light through fiber optic cables and the like to areas inside the body. For example, a fiber optic cable can be inserted through an endoscope into a targeted internal tissue region (e.g., within a vessel or hollow organ) to treat a dysfunction. Alternatively, the photoactivation device  20  may comprise a portable light source that applies light to surface tissue. 
     In the context of the illustrated embodiment (see FIGS.  1  and  3 A/ 3 B), the photoactivation device  20  is sized and configured to be held and manipulated in a single hand, so that it can be wanded or waved to apply light percutaneously to a tissue region where the spider vein or veins are located. 
     In this embodiment (see  FIGS. 3A and 3B ), the photoactivation device  20  includes a low-energy light source  22  carried within a housing  24 . The housing  24  comprises a handle end  26  and a light transmitting end  28 . The handle end  26  is sized and configured to be conveniently gripped by a practitioner. 
     The handle end  26  encloses a control circuit  30  coupled to a self-contained low voltage (i.e., no more than 12 volts), DC power source  32 , such as a battery. The battery  32  is desirably rechargeable, e.g., by a plug-in connector (not shown), or, alternatively, the battery  32  can be configured to be removed and replaced through a lift-off cover (also not shown). The handle end  26  includes an on-off switch  34 , which activates the control circuit  30 . 
     The light source  22  comprises one or more light emitters  36 , which are carried within the housing  24  for transmitting light from the light transmitting end  28  of the housing  24 . The light emitters  36  are coupled to the control circuit  30 . 
     In use, light can be applied to the skin in a tissue region where the spider vein or veins are located by holding the light transmitting end  28  of the housing  24  out of direct surface contact with the skin. Alternatively, light can be applied to the skin in a tissue region where the spider vein or veins are located by placing the light transmitting end  28  of the housing  24  in direct surface contact with the skin. With direct surface contact between the skin and the light transmitting end  28 , reflectance toward the operator is minimized. With direct surface contact between the skin and the light transmitting end  28 , the skin acts as a light guide, allowing output flux to be maximized without localized heating. 
     The light emitters  36  can be, e.g., light emitting diodes (LED&#39;s), emitting light in the wave-length(s) that activates the light reactive agent  14 . The light emitting diodes of a single photoactivation device  20  can be conditioned to deliver multiple wavelengths, so that the photoactivation device  20  can provide a universal platform for different light reactive agents  14 . In the illustrated embodiment, where the light reactive agent  14  is verteporfin, at least one of the wavelengths is 689 nm. In this arrangement, the control circuit  30  may comprise a printed circuit board on which the LED&#39;s are mounted. 
     The light emitters  36  can be arranged in an array sized and configured to focus at common point. Small micro lenses (not shown) may be used to improve focus and adjust the focal distance. In the embodiment illustrated in  FIG. 3A , the light emitters  36  are oriented to focus at a reflecting device  38  carried within the light transmitting end  28 . The reflecting device  38  reflects the light from the light emitters  36  out a portal  40  on the light transmitting end  28 . The reflecting device  38  may comprise, e.g., a surface mirror or a prism. The common focal point for all the light emitters  36  may be slightly short of the reflecting device  38  or slightly beyond the reflecting device  38 , so that the light from the reflecting device mirror will spread to cover an area, or spot size, beyond the portal  40 . The reflecting device  38  may be made adjustable to change the spot size during use. 
     Desirably, for ease of handling, the portal  40  is oriented at an angle to the main axis of the housing  24 , preferably at about 90°. If desired, the light transmitting end  28  could be mounted for pivoting through a range of angles relative to the main axis, and/or for rotation about the main axis, to permit virtually infinite alignment of the emitted light path with the targeted tissue treatment site. 
     Alternatively, as shown in  FIG. 3B , the light-emitters  36  can comprise an array of light emitting diodes carried in the portal  40 , for applying diffused light directly from the portal  40  without use of a reflecting device. 
     As  FIG. 1  shows, a removable transparent cover  42  can be provided to cover light transmitting end  28  during use. The cover  42  can comprise, e.g., plastic film encircled with an elastic material. The materials is selected to be substantially transparent to the wavelength of the light emitted. Following use for a given individual, the cover  42  can be removed and discarded, and replaced with a new cover for the next individual. 
     As  FIG. 2  shows, the various components of the system  10  as just described can be consolidated for use in a functional kit  44 . The kit  44  can take various forms. In the illustrated embodiment, the kit  44  comprises a sterile, wrapped assembly including an interior tray  46  made, e.g., from die cut cardboard, plastic sheet, or thermo-formed plastic material, which hold the contents. The kit  44  also preferably includes directions  48  for using the contents of the kit  44  to carry out a desired procedure. 
     In the illustrated embodiment, every component of the system  10  is contained within the kit  44 . Of course, various components can be provided in separate packaging. In this arrangement, the directions  48  still instruct use of the various components separately provided as a system  10 . 
     The directions  48  can, of course vary. The directions may be physically present in the kit  44 , but can also be supplied separately. The directions  48  can be embodied in separate instruction manuals, or in video or audio tapes, CD&#39;s, and DVD&#39;s. The instructions for use can also be available through an internet web page. The directions  48  instruct the practitioner how to use the system  10  to carry out the intended therapeutic treatment. The directions  48  incorporate a method of treatment using the system  10 . 
       FIGS. 4 to 14  show a representative method of using the system  10  shown in  FIG. 1  to treat a vascular condition such as spider veins, which the directions  48  can express in part or in its entirety. As  FIG. 4  shows, the method identifies a site where the targeted condition exists, i.e., where the spider veins are present. This site is called the targeted treatment site  50 . The spider veins are usually easily identifiable by a trained practitioner. They are often red or blue and close to the surface of the skin. They possess branches or “spider webs” with short jagged lines. Spider veins can be found on the legs and face. They can cover either a very small or very large area of skin. 
     In the illustrated embodiment, the light reactive agent  14  is to be administered intravenously. In this arrangement, an appropriate injection site  52  is identified, as shown in  FIG. 5 . The injection site  52  is where a selected light reactive agent  14  will administered intravenously by the system  10  for delivery to the targeted treatment site  50 . Desirably, the injection site  52  offers venous access at a distance from the targeted treatment site  50  in an upstream blood flow direction (i.e., the injection site  52  is farther from the heart than the treatment site  50 ). In this manner, the light reactive agent  14 , when injected intravenously, is allowed to become systemic and will be conveyed by venous blood flow toward the heart to the targeted treatment site  50 . 
     As  FIG. 6  shows, the method prepares the light reactive agent  14  for introduction. In the illustrated embodiment, prescribed volume of the light reactive agent  14  is drawn into the syringe  18 . The volume to be injected in dependent upon the therapeutic dose that is prescribed, which is, in turn, dependent upon the concentration of the light reactive agent  14  in solution, as well as the morphology of the targeted treatment site  50 . 
     Typically, VISUDYNE® material is commercially reconstituted in saline or glucose solution at desired concentration of about verteporfin 2 mg/mL. At this concentration, a typical dose for a spider vein region can be in the order of 1 cc to 5 cc, but this dosage will of course depend upon the physiology of the individual, including the size and depth of the target treatment site  50 , the skin type of the individual, and the body size of the individual. The dosage can be determined by clinical study by physical measurements and titration, or can be selected empirically based upon general anatomic considerations, or a combination of these and other considerations. 
     As  FIG. 7  shows, the method injects the light reactive agent  14  intravenously at the injection site  52 . In the illustrated embodiment, the syringe  18  needle injects directly into a vein. An IV catheter may be used, through which the light reactive agent  14  is injected by syringe or other suitable IV pumping device. 
     The rate of delivery is dependent upon the nature and dosage of the light reactive agent  14  as well as the physiology of the individual being treated. It is desirable to avoid discomfort to the individual, and the rate of delivery selected has this as its primary objective. 
     It is believed that, given the concentration and volume of the VISUDYNE® material being injected in the illustrated embodiment, an injection period of 20 to 30 seconds is acceptable. 
     A period of time desirably occurs after injection (as the clocks C in  FIGS. 7 and 8  indicate), to allow the light reactive agent  14  to become systemic. As  FIG. 9  shows, verteporfin V, once injected, attaches to lipoproteins LP in the plasma. The lipoproteins LP carry the verteporin V to the targeted treatment site  50 , as  FIG. 10  shows. This exposes endothelium of the spider veins to the verteporin V carried by the lipoproteins LP. 
     The optimal time period to allow systemic distribution of the light reactive agent  14  in this manner to the targeted treatment site  50  following injection can be determined by clinical study by physical measurements, or can be selected empirically based upon general anatomic considerations, or a combination of these and other considerations. 
     As  FIG. 11  shows, after allowing a selected time period after injection to pass, the method operates the photoactivation device  20  to apply light having prescribed characteristics to the targeted treatment site  50 . These prescribed characteristics include the wavelength and may also include, but are not necessarily limited to, a desired intensity, a desired spot size, and a desired duration of exposure. The wavelength will depend upon the light reactive agent  14  selected. The intensity, spot size, and duration of exposure of the applied light will depend upon the physiology of the individual being treated and the operating parameters of the system  10 , e.g., upon the size of the treatment site  50 ; the depth of the treatment site  50 ; the skin type of the individual; the body size of the individual; the distance between the light transmitting end  28  of the housing  24  and the skin surface; the time of exposure; and the pattern of applying the light. Optimal operating characteristics for the photoactivation device  20  can be determined by clinical study by physical measurements, or can be selected empirically based upon general anatomic considerations, or a combination of these and other considerations. The photoactivation device  20  can apply light either without making direct contact with the skin or by making direct contact with the skin. 
     As  FIG. 12  shows, once verteporfin is activated by light in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. The singlet oxygen and reactive oxygen radicals cause local damage to inner wall or endothelium of the veins. Cells outside of contact with the activated verteporfin, however, are left unaffected. 
     Treatment by the system  10  and method just described intentionally causes injury to the inner vein walls. By controlling the clinically parameters above described (i.e., the dosage, delivery time and rate, operating conditions of the photoactivation device  20 , etc.) the nature of the injury can be tightly controlled and localized. 
     The initial injury to the vein wall evokes a healing process (see  FIG. 13 ). During the healing process, the vein heals shut over time. The healing results in shrinkage of the spider vein, and eventually, complete obliteration of the spider veins in the targeted region, as  FIG. 14  shows. 
     It should be appreciated that the devices, systems, methods, and protocols that have been described can provide minimally invasive, cost effective, and patient-friendly treatment of diseases or dysfunctions in all regions of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye. 
     The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims.