JP2010515481A - Meibomian gland treatment - Google Patents

Abstract

  In one embodiment consistent with the present invention, a method of treating a mammalian meibomian gland (10) comprises heat adjusted to a temperature sufficient to dissolve an obstruction in the meibomian gland in an eyelid containing the meibomian gland (104). To clear the gland by bringing the occlusion into a fluidized or (dissolved) suspension and maintaining heat for a period of time sufficient to dissolve the occlusion. The gland can then be mechanically treated to exude fluid from the gland (108), and the procedure is performed during or after the period while the occlusion is still flowing or suspended. The Pharmacological treatment of the gland by subsequent use of a local (local or systemic) drug (112) can then be used to help maintain proper flow of lipids from the gland. This summary should not be considered limiting and some embodiments may deviate from the features described in this summary.

Description

(Cross-reference of related literature)
This application is filed on May 15, 2006 by Korb et al., “Method and,” which claims the benefit of priority of US Provisional Application No. 60 / 700,003, filed July 18, 2005. This is a continuation-in-part of US patent application Ser. No. 11/434054 entitled “Apparator for Training Meibomian Grand Dysfunction”, and further, “Method and Appratus for Gr. A continuation-in-part of US patent application Ser. No. 11 / 434,033 entitled “Dysfunction Employing Heated Medium” and further filed on May 15, 2006 by Korb et al., “Me US patent application Ser. No. 11 / 434,446, entitled “Thod and Apparatus for Treating Gland Dysfunction”, each of which is incorporated herein by reference in its entirety.

(Copyright notice)
Part of the disclosure of this patent specification includes material that is subject to copyright protection. The copyright owner has no objection to reproduction when this patent specification or patent disclosure is displayed as a file or record of the United States Patent and Trademark Office, but otherwise retains all copyrights It is.

  The present invention relates generally to the treatment of mammalian eyes. More specifically, the present invention eliminates heat, which dissolves the specific blockage (or dissolves the substance that binds the solid particles forming the blockage), mechanical action to remove the blockage, blockage is removed. It relates to the treatment of obstruction of meibomian glands by the use of various combinations of subsequent drug treatments.

  The human body includes several glands, including the lacrimal and meibomian glands of the eye, the sebaceous or hair follicle sebaceous glands under the face and the heel, and the mammary gland of the breast. These glands may not work properly due to age, irritation, environmental conditions, cell debris, inflammation, hormonal disorders and other causes. One common disease state of the eyelid gland is restriction or cessation of the natural flow of fluid from the gland caused by obstruction.

  In the human eye, the tear film covering the surface of the eyeball is composed of three layers. The innermost layer in contact with the eyeball surface is a mucus layer composed of many mucins. The middle layer that makes up the majority of the tear film is an aqueous layer, and the outermost layer is a thin layer (less than 250 nm) composed of many lipids known as “Meibum” or “Sebum”. Sebum is an enlarged special sebaceous gland located in both the upper and lower eyelids (thus using “sebum” to describe the secretions), and lipid secretions on the lid margin It is secreted by the meibomian gland with an opening made to drain and forms the lipid layer of the tear film. The typical upper eyelid has about 25 meibomian glands, the lower eyelid has about 20 meibomian glands, and the lower eyelid meibomian glands are somewhat larger than those located in the upper eyelid. The meibomian gland comprises various sac-like acini that drain secretions into the main central duct of the gland. The secretion then proceeds to an opening surrounded by smooth muscle tissue and llyolan muscle which is thought to promote sebum exudation. The meibomian gland opening is open on the inner mucosa and outer skin junction called the mucocutaneous skin transition and on the margin of the eyelid around it.

  Specifically, as shown in the above-mentioned patent application, each meibomian gland has a straight long central conduit whose inner surface is covered with four epithelial layers. Along the longitudinal direction of the central conduit are a number of outwardly inflated structures called acini where gland secretions are produced. The inner lining of each acini differs from the main central conduit in that these special cells supply the meibomian gland secretions. Secretions flow from each acini to the conduit. Although not yet established, it is believed that there is a valve mechanism between the acinar and the central conduit to keep secretion until it is needed when the secretions are drained into the central conduit. Meibomian gland secretions are then stored in the central conduit and released through the opening of each gland onto the lid margin. The blinking and compression of the Lyorang muscle surrounding the meibomian gland is thought to be the primary mechanism that opens the opening for the release of secretions from the meibomian gland.

  The ascending phase of blinking is a kind of protective coating that causes the upper eyelid to pull up a thin layer of lipid secreted by the meibomian gland over the other two layers of tear film and suppress the evaporation rate of the underlying layer Form. Therefore, if the lipid layer is incomplete or an inappropriate amount of such lipids, the evaporation of the water layer is promoted, and eventually itching, cauterization, and irritation, collectively referred to as “dry eye” You will find that it can cause symptoms such as dryness.

  There are many etiologies for dry eye conditions. A common cause of a common dry eye condition is a condition called “Meibomian gland dysfunction” (MGD), a disorder in which the gland is blocked or closed. As used herein, the terms “ocluded” and “obstruction” refer to solid, semi-solid, or if they are associated with meibomian gland dysfunction, Meibomian gland, or meibomian, which has concentrated clotted secretions and / or plugs, leading to compromise, more specifically partially or completely blocked or clogged, leading to secretion reduction or cessation Defined as any component of the gland. Also, when secretion is reduced or restricted, the meibomian glands can be damaged by closure or obstruction, as indicated by the yellowing that indicates an infectious condition, or by another cause, and as a result The protective lipid protective film may be insufficient.

  Meibomian adenitis is an inflammation of the meibomian glands that causes dysfunction of the meibomian glands and is usually accompanied by blepharitis (inflammation of the eyelids). Meibomian gland dysfunction may accompany meibomian adenitis, and meibomian gland dysfunction may develop without obvious eyelid inflammation. Meibomian gland dysfunction is a meibomian gland opening and / or central duct of the gland (canal), or possibly an acinar or acinar valve (as they actually exist) or central duct of the acinus Often is the result of keratotic occlusion that partially or completely blocks the junction. Such obstruction reduces the secretory function of individual meibomian glands. More particularly, these keratinous occlusions can include a combination of bacteria, sebaceous matrix, dead cells and / or detached epithelial cells. See Korb et al., “Meibomian Grand Dysfunction and Contact Lens Intelligence”, Journal of the Optical Association, Vol. 51, No. 3, 1980, pages 243-151. Meibomian adenitis is revealed by visual inspection of the external eyelid, but obstructive meibomian gland dysfunction may not be found even when examined with a slit biomicroscope. This is because there are no apparent signs or the appearance signs are negligible and may be overlooked. Apparent signs of obstructive meibomian gland dysfunction without obvious eyelid inflammation include subtle changes in the meibomian gland opening, overgrowth of the epithelium of the eyelid margin covering the opening, and glandular opening of the gland due to a coagulant acting as an obstruction It can be limited to protrusions only. In severe cases of obstructive meibomian gland dysfunction without obvious eyelid inflammation, changes may be evident, such as serrated or wavy eyelid margins, retraction of the opening, and epithelium covering the opening. Obvious overgrowth as well as protrusion of the opening is included.

  Hormonal changes that occur during menopause, particularly while estrogen levels change, can result in thickening of the oil secreted by the meibomian glands, resulting in clogging of the glandular opening. Furthermore, the reduction of estrogen levels also increases the conditions under which staphylococci can grow. This can result in the movement of bacteria into the gland resulting in a decrease in the secretion rate.

  When the flow of secretion from the meibomian gland is restricted due to the presence of an obstruction, cells on the margin of the eyelid grow over the gland opening, further restricting sebum flow and exacerbating dry eye conditions Has been observed. Other factors that cause or exacerbate meibomian gland dysfunction include behavior such as age, blink impairment, use of computers that weaken normal blinks, contact lens wear and hygiene, cosmetic use, or other Illnesses, especially diabetes.

  Individual meibomian gland conditions range from optimal conditions that produce clear meibomian gland fluids to mild or moderate meibomian gland dysfunctions that produce milky fluids or concentrated or creamy secretions. Various, up to complete blockage where no secretions can be obtained (Korb et al., “Increase in Tear Film Lipid Layer Thickness Flowing Treatment of Meibomian Gland Dysfunction”, LacrimD A. Sullivan, Plenum Press, New York (1994)). Along with meibomian gland dysfunction, a large chemical change in meibomian gland secretions results, resulting in a change in the composition of the naturally occurring tear film, which in turn causes eye diseases commonly referred to as “dry eye”.

  The tear film functions as an individual entity and all layers of the tear film are important, but the lipid layer secreted from the meibomian gland is particularly important. This is because the lipid layer slows the evaporation of the underlying layer and lubricates the eyelids at the blink of a eye, which prevents dry eye and epitheliosis.

  Thus, in summary, the meibomian glands of the eyelids of mammals (such as humans) secrete oil that prevents tear film evaporation and lubricates the eyes and eyelids. These glands can be blocked or clogged by various mechanisms, leading to so-called “dry eye syndrome”. Although not the only cause, meibomian gland dysfunction (MGD) is known to be a major cause of dry eye syndrome. This disorder is characterized by certain types of obstacles that prevent normal lipid secretions from flowing through the meibomian gland or at the surface of the meibomian gland to form the lipid layer of the tear film.

  Such secretions prevent the tear film from evaporating and serve to lubricate the eye, and in the absence of this secretion can cause dry eye syndrome. Meibomian gland occlusion or closure may occur in the main duct of a gland that is narrowed or blocked, or in some cases, including a passage from the acini to the main duct. It exists in the place of.

  The theory is that the meibomian gland acini is equipped with a valve at the junction between the acinar and the main duct of the gland. The inventors believe that, if these valves are present, in theory, these valves will also sometimes occlude and flow from the acinar will be reduced or blocked. These occlusions or closures can have various components.

  In response to these circumstances, various therapeutic modalities have been developed to treat dry eye conditions, including drops to replicate and replace the natural tear film, and cells that produce tears. A variety of heating devices designed to facilitate the removal of clogged meibomian glands, stimulating medications. Another technique involves manually squeezing the gland.

  Brand eye drops such as Refresh (R), Soothe (R), and Systeme (R) are designed to closely replicate the naturally occurring healthy tear film. However, the use and administration of these eye drops is merely a symptom treatment and does not address the root cause. In addition, the use of drops is generally over an indeterminate period, and as a result, long-term use can be cumbersome and expensive.

  Drug modalities have also been presented, such as the use of tetracycline to treat meibomian gland dysfunction, and one such treatment is US Patent Publication No. 2003/2003 entitled “Method for Treating Meibomian Grand Disease”. No. 011426, Pflugfelder et al., US Pat. No. 6,455,583 entitled “Method for Treating Meibomian Green Disease”, and “Use of Tetracyclines for Treating 131”. Is disclosed. However, this treatment has not proven to have universal clinical efficacy and is unnecessary when meibomian gland dysfunction is the result of gland obstruction without infection. The use of corticosteroids for the treatment of meibomian gland dysfunction has also been proposed, as described by Pflugfelder et al., “Non-preserved Topical Corticosteroid for Treatment of Dry Eye, filamentary deratitis, deratitory, In U.S. Pat. No. 6,153,607. Again, this treatment seems to treat the symptoms of dry eye, not a response to the root cause. In addition, the use of locally used androgens or androgen analogs to treat signs and symptoms of acute dry eye in psoriatic keratoconjunctivitis has also been made, which is described in US Pat. No. 5,958,912 and US Pat. No. 6107289, both of which are patented by Sullivan under the name “Ocular Therapeutics in Keratoconjunctivities Sicca Using Topically Applied Androgens or TGF-β”.

  Most knowledgeable physicians recognize that heating is beneficial in treating MGD. Depending on the nature of the occlusion, heating is beneficial to actually melt or loosen the occlusive material and allow the gland to begin producing and draining free lipids and other fluids.

  One modality of heat treatment for meibomian gland dysfunction is disclosed in PCT Application No. PCT / GB2003 / 004782, entitled “Eyleid Margin Wipes Comprising Chemical Means for Temperature Adjustment”. As disclosed in this patent application, wiping means are provided to activate chemicals that heat the wiping means from about 32 ° C. to about 40 ° C. prior to use. A hot wiping means can then be applied to the eyelid and then squeezed by hand to remove clogging of the conduit. This method is also not without defects in that it can exacerbate eyelid irritation due to non-specific heating.

Another method of heating the eyelids and meibomian glands uses near infrared (NIR) radiation. More specifically, two hard eyepatches were attached to the eye mask according to the subject's interpupillary distance. The eye mask was held in place with an elastic headband. Each eye patch used 19 light emitting diodes emitting near infrared radiation from 850 nm to 1050 nm peaking at 940 nm. This device produced 10 mW / cm ² of energy that was powered. Goto, E .; Et al., “Treatment of Non-Informed Obstructive Meibomian Gland dysfunction by an Infrared War Compression Device,” p. Pp. 140, British Journal of 140. This device is designed as a non-contact infrared heating mask using IR light emitting diodes. However, there are many potential problems with the use of infrared heating mechanisms. For example, IR heating can penetrate to the cornea in the back of the eyelid, which is detrimental and ultimately can cause cataracts and other damage. In addition, the IR mask heater applies any pressure on the eyelid that we have determined to be useful in removing obstructions (despite being described as a pressurizing device). is not. Moreover, tests performed on samples of this mask revealed that the mask actually produced very little heat, despite the potential danger.

  US Patent Publication No. 2004/0237969, entitled “Therapeutic Eye and Eye Lid Cover”, also describes the delivery of heated saturated air to the eyelids and in particular to the meibomian glands to heat the meibomian glands. Protective eyeglasses are included. Regarding the heat treatment of the eye, “Tear Film Lipid Layer Thickness and Oximal Strain of Human Medicine” was published on pages 1-4 of Eye (2004) by Mitra et al. Is also discussed.

  In US Patent Publication No. 2003/0233135, named Yee's “Method and Apparatus for Presenting and Treating Eyelid Problems”, the present invention is intended to promote exudation of meibomian gland secretions. I am trying to remove clogging of meibomian glands by electrical stimulation.

US Patent Publication No. 2003/011426 US Pat. No. 6,455,583 WO99 / 58131 pamphlet US Pat. No. 6,153,607 US Pat. No. 5,958,912 US Pat. No. 6,107,289 PCT Application No. PCT / GB2003 / 004782 Specification US Patent Publication No. 2004/0237969 US Patent Publication No. 2003/0233135 US patent application Ser. No. 11/434054 US patent application Ser. No. 11/434033

Korb et al., “Meibomian Grand Dysfunction and Contact Lens Intelligence”, Journal of the Optical Association, Vol. 51, No. 3, 1980, pages 243-151. Korb et al., “Increase in Tear Film Lipid Layer Thickness Flowing Treatment of Meibomian Gland Dysfunction, page 29, Lacrimal Gland, Der. A. Sullivan, Plenum Press, New York (1994) Goto, E .; , “Treatment of Non-Infrared Obstructive Meibomian Grand dysfunction by an Infrared War Compression Device,” p. 3-140, British Journal of Op. Mitra et al., “Tear Film Lipid Layer Thickness and Ocular Comfort after Meibomian Therapeutic Via Lent Heat with a Novel Device in Year 4”

  The purpose of some embodiments consistent with the present invention is to provide a method for the treatment of mammalian eyelids.

  Another object of some embodiments consistent with the present invention is to first and the upper and / or lower eyelids of one or both eyes to help remove specific types of occlusions in or around the meibomian glands. A method of treatment that produces a flow of lipids from the meibomian glands of the eyelids, followed by pharmacological treatments that help maintain lipid flow and otherwise promote eye lubrication Is to provide.

  In one embodiment consistent with the present invention, a method of treating a mammalian meibomian gland comprises applying heat adjusted to a temperature sufficient to dissolve the occlusion in the meibomian gland to an eyelid containing the meibomian gland to reduce the occlusion. To clean the gland by allowing it to flow or (dissolved) in suspension, dissolve the obstruction, and maintain heat for a period of time sufficient to place the obstruction in fluid or (dissolved) suspension. Accompany. The gland can then be mechanically treated to exude fluid from the gland, and the treatment is performed during or after the period, while the occlusion is still flowing or suspended. In most cases this should be done within about 90 seconds from the end of the period. Pharmacological treatment of the gland with subsequent (local or systemic) drug use is then used to help maintain proper flow of lipids from the gland, otherwise the eye It can help promote lubrication.

  According to some embodiments, the duration can be about 10 to 60 minutes, with about 15 minutes generally being suitable for mild to moderate cases of MGD. More severe cases may require 30 to 45 minutes of treatment, and extremely severe cases may require up to 60 minutes of heat treatment. These times assume a target temperature of 44 to 47 degrees, preferably 45 degrees Celsius, and are probably shortened somewhat at higher temperatures or somewhat extended at lower temperatures. The temperature can be in the range of 37 degrees Celsius or higher.

  In some embodiments, the mechanical treatment is to squeeze fluid from one or more of the glands while applying constant pressure, vibration energy, mechanical energy, pulsating mechanical stimulation, squeezing, and simultaneously heating. It is performed by exuding or by applying a vibration stimulus to the eyelid while simultaneously heating.

  In another embodiment, a method of treating meibomian gland dysfunction in a mammal in which at least a portion of a naturally occurring secretion stream from the duct opening is blocked by closure comprises a regulated heat source, a gland duct Proximity to the opening, application at a selected temperature for a selected time sufficient to soften or liquefy at least a portion of the occlusion, closure of the closure so that at least a portion of the closure is removed Mechanically treating the ductal opening while at least partially softened or liquefied, followed by facilitating the free flow of lipids from the meibomian gland, otherwise lubricating the eye With treatment with drugs that help promote the disease.

  In another embodiment, a method of treating meibomian gland dysfunction in a mammal in which at least a portion of a naturally occurring secretion stream from the duct opening is blocked by closure comprises a regulated heat source, a gland duct Proximity at the selected temperature for a selected time sufficient to loosen, subdivide, break, soften or liquefy at least part of the closure in proximity to the opening, adjusted Mechanical treatment of the ductal opening so that at least a portion of the closure is removed before the effect of applying the heat source is reversed, followed by free flow of lipids from the meibomian gland Encouraging and otherwise treating with drugs that help promote eye lubrication.

  The above summary is intended to illustrate exemplary embodiments that should be properly understood in conjunction with the following detailed description, and is not intended to limit the scope or meaning of the appended claims.

  Several exemplary embodiments illustrating configurations and methods of operation, together with objects and advantages, will be better understood when the following detailed description is taken in conjunction with the accompanying drawings.

It is the figure which drew the upper eyelid and lower eyelid which show the meibomian glands. 3 is a cut-away view showing an example of a meibomian gland 20. FIG. FIG. 3 is a cutaway view of meibomian gland 20 showing several occluded regions. 6 is a graph showing the inner and outer surface temperatures of the eyelid while the outer surface of the patient's eyelid is heated to about 45 degrees Celsius. 6 is a flow diagram illustrating a treatment process consistent with some embodiments of the present invention. 6 is a flow diagram illustrating another course of treatment consistent with some embodiments of the present invention.

  While the present invention allows for many different forms of embodiments, such embodiments of the present disclosure should be considered as an example of principles and limited to only the specific embodiments illustrated and described. With the understanding that it is not intended to do so, specific embodiments are shown in the drawings and are described in detail herein. In the following description, like reference numerals are used to indicate the same, similar or corresponding parts in the several views of the drawings.

  The term “plurality” as used herein is defined as “two or more”. The term “another” as used herein is defined as “at least one second or more”. The terms “including” and / or “having”, as used herein, are defined as “comprising” (ie, non-exclusive wording). The term “coupled” as used herein is defined as “connected” but is not necessarily directly connected and is not necessarily mechanically connected. Not necessarily. The term “program” or “computer program” or similar terms, as used herein, is defined as “an instruction sequence designed to execute on a computer system”. Is done. “Program” or “computer program” includes subroutines, functions, procedures, object methods, object implementations, executable applications, applets, servlets, source code, object code, shared libraries / dynamic load libraries and / or computers Other instruction sequences designed to execute on the system may be included.

  Throughout this specification, reference to “one embodiment”, “some embodiments”, “one embodiment” or similar phrases means that a particular feature described in connection with the embodiment, It is intended that the structure or characteristic be included in at least one embodiment of the invention. Thus, the appearances of such phrases in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner without limitation in one or more embodiments.

  As used herein, the term “or” should be construed as inclusive or in any one or any combination. Thus, “A, B or C” means “A; B; C; A and B; A and C; B and C; any of A, B and C”. An exception to this definition occurs only when a combination of elements, functions, steps or actions is in some way inherently mutually exclusive.

  As mentioned above, meibomian gland dysfunction (MGD) is known to be a major cause of dry eye syndrome. The disorder is characterized by some sort of blockade in the meibomian gland that prevents normal lipid secretions from flowing out of the gland through the opening and into the tear film. An obstruction or closure of the meibomian gland may be present in the gland opening, and possibly in other locations including the narrowed or blocked main gland conduit. Meibomian gland acini are equipped with valves at the junction of the acinar and the main duct of the gland, which may in some cases become obstructed to reduce or block flow from the acini. The theory has been advocated. These occlusions or closures can have various compositions.

  Referring now to FIG. 1, the location of the meibomian gland 10 is shown on the upper eyelid 12 and the lower eyelid 14, respectively. As briefly mentioned above, the upper eyelid contains about 25 meibomian glands and the lower eyelid contains about 20 meibomian glands, but there is considerable variation. As shown in the cross-sectional view of one gland 10 in FIG. 2, each gland is open to the eyelid margin with a central conduit or tube 18 through which secretions flow from the acinus 19, and the secretions are there during blinking. And an opening 20 that flows out of the tear film and is added to the tear film. It can be seen that each gland varies in size depending on its position in the eyelid and the opening 20 is narrower than the central conduit 18.

  The occlusion composition depends on the etiology that caused the occlusion. However, in most cases observed to date, obstruction is caused by dead cells, bacteria, exfoliated cells, and exfoliated cells that have aggregated as keratinous agglomerates, emulsions, concentrated or creamy secretions. A combination or any combination of these in solid, semi-solid and concentrated form. Referring to FIG. 3, a simplified diagram of an example of an occlusion for gland 10 is shown. This example does not necessarily represent any meibomian gland occlusion, as described above, but examples include a solid or semi-solid or concentrated plug 24 that completely closes the opening 20 of the gland 10. It is shown. Another occlusion 26 is shown at the junction with the central conduit from one of the acini. As mentioned above, this can be the site of a valve within the glandular structure, but embodiments consistent with the present invention should not be limited to the theory of actual meibomian glandular structure.

  Although several treatments have been proposed to restore these glands to normal function, most physicians recognize that heating is beneficial in treating MGD. Depending on the nature of the occlusion, heating may actually dissolve or loosen the occluding material or substances that bind to the solid particles that form the occlusion, allowing the gland to freely initiate production and excretion of lipids and other fluids It will be beneficial. While it has been found that there are many deficiencies in the heat treatment methods described in the background section of this specification, the heat methods described in the aforementioned co-pending applications can be effective and beneficial. I know it. Generally, these devices provide controlled heating of the eyelid (measured on the outer surface of the eyelid) to a treatment temperature above 37 degrees Celsius, more preferably 45 degrees Celsius, by direct contact with the eyelid. Occurs between about 44 and 47 degrees Celsius. However, other devices may be used that are placed close to the eyelid to apply heat to the meibomian glands.

  It has been observed that the outer surface of the human eyelid is about 1 to 2 degrees Celsius cooler than body temperature, although there is some variation. Increasing the temperature to at least 37 degrees can begin to provide therapeutic effects to mild cases of MGD. One convenient range for treatment is from 44 degrees Celsius to 47 degrees Celsius, and a target temperature of 45 degrees Celsius has proven effective and comfortable for the patient. In some embodiments, mechanical energy treatment is performed, preferably with a heated instrument, during the period or immediately after the end of the period to further maintain the occluded flow state. Mechanical energy treatment includes, but is not limited to, mechanical action including vibration action, squeezing, mechanical pulsatile pressurization, squeezing and / or other actions that exude fluid from the gland and / or expand the conduit or opening of the meibomian gland It can be performed by any mechanism including pressurization. The mechanical energy can take any form that applies mechanical pressure to the meibomian gland to help block or push the occlusion out of the gland while the occlusion softens with heat. Higher temperatures (such as 50 to 55 degrees Celsius) can be used (or applied intermittently over a shorter period of time), especially if the eyelid is under anesthesia, in which case the patient is permanently A much higher temperature treatment over a shorter period of time can be used without damage. In general, higher temperatures can be used for shorter periods of time. Furthermore, the temperature and time used should be individualized depending on the severity and tolerance of the patient's condition. Patients with white skin are generally considered less tolerant of heat than patients with dark skin, and patients with dark skin tend to be less prone to inflammation as a result of exposure to heat I know that. Treatment time and / or temperature can be adjusted to accommodate these differences. Each of the above temperatures refers to the temperature measured on the outer surface of the eyelid.

  Also, in some embodiments, the patient feels more comfortable when the treatment starts at a lower temperature and the temperature is raised over time. Therefore, the temperature should be adjusted, where adjustment should be taken to mean that the actual temperature applied to the outer surface of the eyelid is controlled or adjusted in a repeatable manner. is there. The heating temperature profile can be a constant temperature, it can have an increase, decrease, highest point, lowest point, it can be added intermittently, it can also be adjusted using various characteristics, etc. Although possible, such a profile should be adjusted to be repeatable. It has also been found that adjusting the temperature can produce an average temperature that is higher than a certain temperature, which is useful in some applications.

  This temperature can be maintained at a treatment temperature for a treatment period of about 10 to 60 minutes (or some patients have been found to be safe and beneficial even beyond this time). The fact (by dissolution of substances that bind the solids together) during mechanical treatment of lipids and other fluids from meibomian glands during or after such treatment with controlled heat It has been found that occlusions that dissolve or remain in suspension are removed. In the above application, fluid movement from the gland containing dissolved or suspended material that exerts a wide squeezing action on the eyelid to exude fluid or suspension or to cause occlusion or closure An apparatus is disclosed that mechanically stimulates the device in another way. In some cases, continuous moderate pressure on the eyelids can help exudate fluids and suspensions, and vibration can be used simultaneously with heating or immediately after heating. As used herein, the term “melted” should be interpreted to include the state in which solid particles remain suspended in a liquid fluid.

  In some embodiments, such a device for applying regulated heat of the eyelids is described in Korb et al., “Method and Apparatus for, filed May 15, 2006, incorporated herein by reference. US Patent Application No. 11/434054 entitled “Treating Meibomian Grand Dysfunction” and Steve Glenn et al., Filed May 15, 2006, entitled “Melting Media Grand Obstrations US Patent Application No. 11”. / 434033 specification. In some embodiments, the apparatus uses a heating unit comprising a heating element that generates heat when an electrical signal is applied. A temperature regulator applies an electrical signal to the heating element to achieve heating of the heating element to a specified temperature range. The eyelid connection mechanism couples the heating unit to the eyelid to achieve controlled heating of the eyelid within a specified temperature range.

  Such a device provides controlled heating up to a certain treatment temperature. The conventional heating pad and IR heating mechanism described in the background section above do not provide controlled and controlled heating at the treatment temperature and are described in the above referenced patent application incorporated herein. Less effective than regulated heat applied using existing equipment.

  In another embodiment disclosed in this patent application, an apparatus for providing controlled heating to at least one of a patient's eyelids comprises a heating unit that generates heat when an electrical signal is applied. A heating element having a first surface and a second surface, a thermal heat sink coupled to the first surface of the heating element to transfer heat from the heating element to the eyelid, and reducing heat loss from the second surface In order to do so, a heat insulating material coupled to the second surface of the heating element and a back plate coupled to the heat insulating material are provided. A temperature regulator applies an electrical signal to the heating element to achieve heating of the heating element to a specified temperature range. Protective eyeglasses suitable for attaching to the patient's head and covering the patient's eyelid with a lens piece are provided, and the lens piece has a screw hole. The threaded shaft passes through the threaded lens piece and couples to the heating unit at the back plate so that the heating unit can be moved into contact with the eyelid by screwing the shaft into the hole until it contacts the eyelid .

  In these embodiments, many variations are possible including, but not limited to, providing a sensor that senses temperature and provides temperature information to the temperature regulator. In some embodiments, the eyelid connection mechanism comprises protective eyeglasses that are adjustably coupled to the heating unit to move the heating unit into contact with the eyelid. The protective glasses are adjustably coupled to the heating unit by means of a screw connection, so that the position of the heating unit can be adjusted by a screwing operation. In some embodiments, the heating unit comprises a thermal heat sink coupled to the surface of the heating element to conduct heat from the heating element to the eyelid. The heat sink may be, for example, at least one of a heat conductive rubber member, a heat conductive silicon member, an encapsulated fluid-containing member, and a solid conductive member. A heat transfer gel, cream or liquid can be placed between the heat sink and the eyelid to improve heat transfer from the heat sink to the eyelid.

  In some embodiments, the heating unit comprises a thermal insulator coupled to the surface of the heating element to reduce heat loss from the heating unit in directions other than toward the eyelid. The thermal insulation may in some embodiments be one of a non-thermally conductive foam, a non-thermally conductive rubber element, a non-thermally conductive solid element. The temperature regulator may apply a pulse width modulated electrical signal to the heating element to regulate the heat generated by the temperature regulator, and the pulse width modulated electrical signal may be generated under the control of a control processor. .

  In some embodiments, the temperature regulator incorporates a switch that selectively applies an electrical signal to the heating element to regulate the heat generated by the temperature regulator. The electrical signal can be at least one of a current and a voltage that are selectively applied to the heating element under the control of the control processor. The heating unit may have a flexible part that touches the eyelid to fit the eyelid, or a hard part that touches the eyelid shaped to fit the shape of the eyelid, a combination of both. May be good. The heating unit may have an adhesive for attaching the heating unit directly to the eyelid, and may be attached to the eyelid using an adhesive tape.

  In some embodiments, the user interface allows the user to set treatment time and / or temperature. In some embodiments, a vibration generator generates eyelid vibration that stimulates secretion from the meibomian gland, and the vibration generator provides mechanical energy having both amplitude and frequency to the eyelid.

  Other heating and / or pressure inducing devices are also disclosed in the above referenced patent application, which is hereby incorporated by reference.

  Therefore, taking into account the above, mechanical treatment using, for example, constant force, squeezing (such as by hand squeezing), squeezing operation or vibration immediately after or during treatment with heat Can be applied to the eyelid to facilitate removal of fluid or suspension from the meibomian glands. If mechanical treatment is performed after heat treatment, it should be performed while the obstructive substance of the meibomian gland is in a dissolved state immediately after heat treatment.

  Referring now to FIG. 4, the graph shows the inner and outer eyelid surfaces when a constant heat source of approximately 45 degrees Celsius is applied to the subject patient. It should be noted that the circulatory system attempts to regulate the temperature of the eyelid and blood flow increases with heating. In this patient, it took about 4 minutes for the outer surface of the eyelid to reach about 45 degrees Celsius, and the inner surface of the eyelid did not reach this temperature at all, probably due to the body's regulatory mechanisms. Thus, when a 45 degree constant heat source is used, it takes at least about 4 minutes to stabilize the eyelid temperature and reach the treatment temperature. The graph also shows that when the heat source is removed from the eyelid, the temperature drops rapidly to body temperature. In almost any case, the temperature falls within 2 to 3 minutes, and more commonly it takes only about 30 to 90 seconds for the temperature of the patient's eyelids to drop. In this example, the temperature dropped rapidly over the first 30 seconds after heat removal. During this short period, some or all of the dissolved occlusion can reconsolidate. Thus, if hand squeezing is performed following heating, hand squeezing should be performed immediately or within about 90 seconds (the interval is preferably shorter, such as within 30 seconds), or In any case, the effect of applying a regulated heat source should be done before retreating so that at least part of the closure is removed. Thus, from this graph, it will be clear that the conventional technique using a hot compress is substantially less effective if hand squeezing is not performed in a very short time thereafter. Furthermore, if the compress cools before hand squeezing, the compress will provide the least source benefit to a patient suffering from severe obstruction.

  It has been found that the problem with most pharmacological treatment modalities for dry eye syndrome is that the drug cannot affect MGD when the disorder involves glandular obstruction. That is, currently known drug treatments alone cannot remove the clogging of meibomian glands to allow lipid flow. Antibiotic therapy, steroid therapy, or other pharmacological treatments are useful for other causes of dry eye, but are ineffective when associated with obstruction of the meibomian glands (or at best provide temporary relief of symptoms) I know that. Many drugs are useful in promoting lipogenesis and meibomian gland flow, but such lipogenesis is not effective and can also be counterproductive if secretions cannot exit the gland . Indeed, the promotion of lipogenesis may cause further meibomian gland damage and gland inflammation.

  Other drugs promote the lubrication function of the eye by promoting the production of tears or otherwise promoting tear film improvement. When used alone, such treatment may be ineffective or only partially effective, but when used after meibomian gland cleansing, all components of the tear film are normal Normal or near normal production can be restored. Thus, many drugs are suitable for further improving the tear film and can be extremely beneficial after the meibomian gland returns to more normal function.

  Therefore, once fluidity is restored to the meibomian gland by heating and manual treatment (pressurization, vibration, pulsation, hand squeezing, etc. during or after treatment), treatments with various drugs are treated with lipids from the gland. Can help to maintain the flow of Thus, referring to FIG. 5, a treatment starting from 100 is shown, and then at 104 as produced by the various devices described in the aforementioned patent application incorporated by reference. Controlled heat is applied to the eyelid. Preferred heating is greater than 37 degrees Celsius, a thermal range between about 44 and 47 degrees Celsius is preferred and targets 45 degrees Celsius. However, higher degrees Celsius over a shorter period of time provide therapeutic efficacy but can also have the side effect of mild skin burns that do not cause persistent damage. Below this temperature range, the treatment tends to be less effective or ineffective. Temperatures above this range can cause significant patient discomfort, eyelids and possibly eye damage. At higher temperatures in the range, the patient may feel the heat somewhat uncomfortable, but the treatment time can be shortened and the discomfort can be relieved by anesthesia. Lower temperatures within the range are effective, but generally require longer heating times.

  As a starting point by rule of thumb, a relatively constant 45 degrees and 15 minutes generally works well for many patients with mild to moderate MGD without undue discomfort to the patient. Depending on the severity of the MGD, temperature, anesthesia used, and patient tolerance, a time range of about 10 to 60 minutes or even more may be used. During the experiment, more than 1 hour was used without any apparent adverse effects.

  After the heat treatment is complete (and / or during heat treatment), at 108, the mechanical modality described above is used to exude fluid or suspension from the meibomian gland while the occlusion is in a dissolved state. In either of these cases, a mechanical force can be applied. When using gland squeezing, it is desirable to heat any equipment used in the squeezing process to help heat or maintain the gland heat at the same time as squeezing.

  Hand squeezing of glands, when used alone, can be painful, invasive and inconsistent due to variations in hand control and / or manipulation, and this MGD The method of treatment can be very uncomfortable for the patient because the doctor needs to squeeze the gland, but this technique proves useful as a step in the process of selective use in difficult cases . There are about 45 to 50 glands between the upper and lower eyelids, so it is very time consuming to squeeze each gland, so it is inefficient for the doctor and patient for the patient It is pain. However, as mentioned above, when combined with an automatic squeezing device that helps further clean the heavily occluded gland to improve the normal flow of lipids that flow from the gland through the opening to the tear film Can be beneficial. After heat treatment, in general, the effect of squeezing the secretions from the obstructed gland is dramatically improved compared to when used alone, with less patient discomfort and better results. As mentioned above, when using gland squeezing, heating any equipment used in the squeezing process to help heat or maintain the gland heat at the same time as squeezing Is desirable.

  After closure and other foreign bodies are removed from the meibomian gland at 104 and 108 and lipid flow is restored, 112 minimizes gland inflammation, removes infection, prevents further blockage, and dilutes the lipid. Any of a variety of drugs (local or systemic) to promote tear production and improve tear film composition, or promote improved free flow of lipids or eye lubrication Any other pharmacological modality can be used to treat the meibomian glands. Pharmacological treatment may be performed over a short period of time (such as to remove an infection or inflammatory condition), a drug that dilutes lipids, reduces inflammation, or treats other modalities of dry eye syndrome (Such as in the case of) and may be performed for ongoing treatment. The process ends at 116.

  Many drugs have been proposed for the treatment of dry eye syndrome, any of which can be effective or more effective once the obstruction in the meibomian glands is removed. Among the drugs that can be utilized are, but are not limited to, antibiotics such as topical or oral tetracyclines and chemically modified tetracyclines, testosterone, topical or oral corticosteroids, topical androgens or androgen analogs, omega-3 fatty acids such as fish oil Compounds, raennecks, enzymes that promote lipogenesis, drugs that stimulate the production of enzymes that promote lipogenesis, and any drugs that act as secretagogues that improve the secretion of meibomian gland secretion or other tear components. Androgens and androgen analogs and TGF-β have been reported to act as secretagogues that improve meibomian gland secretion, and there are drugs that replace or promote the production of any tear component There are promising drugs. Those skilled in the art will appreciate that these ingredients are illustrative examples of suitable drugs and that other pharmacological ingredients may be utilized in view of the teachings of the present invention. Furthermore, it can be seen that multiple modalities may be involved in the development of dry eye syndrome, but treating only one modality may not provide sufficient resolution. Thus, restoration of normal or near normal flow of lipids from the meibomian glands is only part of the solution, and pharmacological treatment of one or more other modalities of the disease that restore normal tear film. Can be accompanied. However, when accompanied by severe MG dysfunction, other modalities alone are likely not satisfactory.

  With reference to FIG. 6, the various described in the above referenced patent application, which is incorporated herein by reference, at 104, as in the case of the above-described therapies, is then started. One variation of the above treatment is described in which controlled heat as generated by the device is applied to the eyelid. The preferred range for such heating is again between about 44 and 47 degrees Celsius, targeting 45 degrees Celsius. Again, depending on the severity of the condition, treatment temperature and patient tolerance, a time range from about 10 minutes to 60 minutes and beyond may be used.

  In this embodiment, during heat treatment, including those referred to above and incorporated by reference to squeeze fluid or suspension from the meibomian gland while the occlusion is in liquid or suspension during heating. Thus, in any of the aforementioned mechanical modalities, mechanical force can be applied at 138.

  Depending on the combination of the patient's response to heat and the simultaneously applied mechanical force at 138, at 142, additional force can be applied immediately after removal of heat. Again, it is preferred that the heat be maintained during squeezing or during application of force as described above. That is, any probe or other instrument used during squeezing is preferably heated to help maintain the occlusion in a liquid or suspended state. Such a force can also be applied by squeezing the eyelid by hand at the appropriate location where the occlusion appears to remain, and automated mechanical means may be used if available.

  104, 138 and 142, after closure and foreign bodies have been removed from some or all of the meibomian glands, as above 112 at 112 minimizes gland inflammation, removes infection, prevents further blockade, Any other pharmacology that uses various drugs to dilute (local or systemic) or promote free flow of lipids or otherwise improve tear film improvement Modal modalities can be used to treat meibomian glands. As mentioned above, pharmacological treatments may be performed over a short period of time (such as to remove an infection or inflammatory condition) and (of a drug that dilutes lipids, improves tear components and reduces inflammation). May be performed for ongoing treatment (as in some cases). The process ends at 150.

  The above process, whether with the process of FIG. 5 or with the process of FIG. 6, is repeated at time intervals as necessary to produce and maintain the proper flow from the meibomian gland. Or may be interchanged. In some patients, such treatment, or portions of treatment, may need to be repeated periodically so that lipids continue to flow from the meibomian glands.

  Thus, according to some embodiments consistent with the present invention, a method of treating a mammalian meibomian gland regulates an eyelid containing a meibomian gland to reach a temperature sufficient to dissolve an obstruction in the meibomian gland With the applied heat and cleansing the gland by dissolving the occlusion and maintaining the heat for a period of time sufficient to place the occlusion in a fluid or (dissolved) suspension. The gland can then be mechanically treated to squeeze fluid or suspension out of the gland, the mechanical treatment being performed while the occlusion is still dissolved during or after the period Is done. The process can be improved by heating the applied therapeutic device to maintain the temperature and dissolved state of the occlusive material. Pharmacological treatment of the gland with subsequent (local or systemic) drugs can then be used to help maintain the proper flow of lipids from the gland.

  According to some embodiments, the duration can be about 10 to 60 minutes, with about 15 minutes being generally suitable for mild to moderate cases. The temperature should be greater than 37 degrees Celsius, and the preferred range is approximately 44 to 47 degrees Celsius targeting 45 degrees Celsius on the outer surface of the eyelid, and this range should be effective and comfortable for the patient. I know it. In some embodiments, the mechanical treatment is performed as soon as possible after heating, preferably within 30 to 90 seconds, so that the occlusion remains dissolved during the expression process. In some embodiments, the mechanical treatment may include applying a constant pressure, squeezing, exuding fluids or suspensions from one or more of the glands while simultaneously heating, or eyelids while simultaneously heating Performed by at least one of applying a vibration stimulus to the. Many variations and alternative embodiments will occur to those skilled in the art in view of the teachings of the present invention.

  While several embodiments have been described above, many alternatives, modifications, substitutions and variations will become apparent to those skilled in the art in light of the above description.

Claims (42)

A method for treating a mammalian meibomian gland comprising:
Applying a controlled heat to the eyelid containing the meibomian gland that dissolves the obstruction in the meibomian gland and reaches a temperature sufficient to place the obstruction in a dissolved state;
Maintaining heat for a period of time sufficient to dissolve the occlusion and place the occlusion in a dissolved state;
Meibomian gland by mechanically treating the gland by exuding the dissolved occlusion from the gland, followed by drug use, during or after the period, while the occlusion is still dissolved Treating.   The method of claim 1, wherein the period is from about 10 minutes to 60 minutes.   The method of claim 1, wherein the mechanical treatment is performed using a heated instrument.   The method of claim 1, wherein the temperature reaches about 45 degrees Celsius.   The method of claim 1, wherein the temperature reaches about 44 to 47 degrees Celsius.   The method of claim 1, wherein the temperature is at least 37 degrees Celsius.   The method of claim 1, wherein the mechanical treatment is performed within 3 minutes after the end of the period.   The mechanical treatment includes exuding so as to squeeze the dissolved occlusion from one or more of the glands, applying mechanical energy stimulation to the eyelid, squeezing the eyelid, applying a certain pressure to the eyelid The method of claim 1, wherein the method is performed by at least one.   The method of claim 1, wherein the drug is a topical drug.   The method of claim 1, wherein the drug is a systemic drug.   Drugs include antibiotics, topical tetracyclines, oral tetracyclines, topical corticosteroids, oral corticosteroids, topical androgens, topical androgen analogs, TGF-β, omega-3 compounds, enzymes that promote lipogenesis, enzymes that promote lipogenesis 2. The drug selected from the group consisting of a drug that stimulates production, a drug that acts as a secretagogue that improves meibomian gland secretion, and a drug that replaces or promotes the production of any tear component. The method described.   12. The method of claim 11, wherein a plurality of the drugs are selected.   The method of claim 1, further comprising applying and maintaining heat adjusted at time intervals to maintain fluid flow from the meibomian glands.   14. The method of claim 13, further comprising repeating the mechanical treatment at time intervals to maintain fluid flow from the meibomian glands. A method for treating a mammalian meibomian gland comprising:
Applying a regulated heat of at least about 37 degrees Celsius to the eyelid containing the meibomian gland to a temperature sufficient to dissolve the obstruction in the meibomian gland and place such obstruction in a dissolved state;
Maintaining the heat for a period of time sufficient to dissolve the occlusion and place the occlusion in a dissolved state from about 10 to 60 minutes;
By mechanically treating the gland by exuding the dissolved occlusion from the gland, and subsequent use of the drug, which is performed while the occlusion is still dissolved, prior to 90 seconds after the expiration of the period Pharmacological treatment of the gland.   The method of claim 15, wherein the temperature reaches about 44 to 47 degrees Celsius.   The method of claim 15, wherein the temperature reaches about 45 degrees Celsius.   The mechanical treatment exudes so as to squeeze the dissolved occlusion from one or more of the glands, applies a vibration stimulus to the eyelid, squeezes the eyelid, or applies a constant pressure to the eyelid or The method of claim 15, wherein the method is performed by at least one of applying intermittent pressure.   16. A method according to claim 15, wherein the drug is a topical drug.   16. The method of claim 15, wherein the drug is a systemic drug.   The method of claim 15, wherein the mechanical treatment is performed using a heated instrument.   Drugs include antibiotics, topical tetracyclines, oral tetracyclines, topical corticosteroids, oral corticosteroids, topical androgens, topical androgen analogs, TGF-β, omega-3 compounds, enzymes that promote lipogenesis, enzymes that promote lipogenesis 16. A drug selected from the group consisting of a drug that stimulates production, a drug that acts as a secretagogue that improves meibomian gland secretion, and a drug that replaces or promotes the production of any tear component. The method described.   24. The method of claim 22, wherein a plurality of the drugs are selected. A method for treating a mammalian meibomian gland comprising:
Applying a controlled heat in the range of about 44 degrees Celsius to 47 degrees Celsius to the eyelid containing the meibomian gland to a temperature sufficient to dissolve the obstruction in the meibomian gland and place the obstruction in a dissolved state;
Maintaining the heat for a period of time sufficient to dissolve the occlusion and place the occlusion in a dissolved state from about 10 to 60 minutes;
During the period or within 90 seconds after the end of the period, while the occlusion is still dissolved, performed using a heated instrument, the gland is removed by leaching fluid or suspension from the gland A method comprising mechanically treating and subsequently pharmacologically treating the gland by use of a drug.   A mechanical treatment exuding fluid or suspension from one or more of the glands, applying mechanical energy stimulation to the eyelid, applying vibrational energy to the eyelid, squeezing the eyelid, or 25. The method of claim 24, performed by at least one of applying a constant pressure or intermittent pressure to the eyelid.   25. The method of claim 24, wherein the drug is a topical drug.   25. The method of claim 24, wherein the drug is a systemic drug.   Drugs include antibiotics, topical tetracyclines, oral tetracyclines, topical corticosteroids, oral corticosteroids, topical androgens, topical androgen analogs, TGF-β, omega-3 compounds, enzymes that promote lipogenesis, enzymes that promote lipogenesis 25. Selected from the group consisting of a drug that stimulates production, a drug that acts as a secretagogue that improves meibomian gland secretion, and a drug that replaces or promotes the production of any tear component. The method described.   28. The method of claim 27, wherein a plurality of the drugs are selected.   25. The method of claim 24, further comprising repeating applying and maintaining controlled heat at time intervals.   32. The method of claim 30, further comprising repeating mechanical treatment at time intervals to maintain fluid flow from the meibomian glands. A method of treating meibomian gland dysfunction in a mammal in which at least a portion of the naturally occurring secretion stream from the duct opening is blocked by closure, comprising:
a) applying a conditioned heat source at a selected temperature proximate to the duct opening and for a selected time sufficient to soften or liquefy at least a portion of the obstruction;
b) mechanically treating the ductal opening while at least part of the closure is still softened or liquefied so that at least part of the closure is removed, and c) Treating with a drug that promotes free flow of lipids from the meibomian glands.   35. The method of claim 32, wherein the time selected is from about 10 minutes to 60 minutes.   35. The method of claim 32, wherein the selected temperature reaches approximately 44 to 47 degrees Celsius.   The method of claim 32, wherein the temperature is at least 37 degrees Celsius.   34. The method of claim 32, wherein the drug is a topical drug.   35. The method of claim 32, wherein the drug is a systemic drug. A method of treating meibomian gland dysfunction in a mammal in which at least a portion of the naturally occurring secretion stream from the duct opening is blocked by closure, comprising:
a) Select a controlled heat source for a selected time sufficient to loosen, subdivide, break, soften or liquefy at least a portion of the closure in proximity to the ductal opening Applying at a temperature,
b) mechanically treating the gland duct opening so that at least a portion of the closure is removed before the effect of applying a regulated heat source is regressed; and c) subsequently the mammal is treated with the meibomian gland Treating with a drug that promotes free flow of lipids from the body.   40. The method of claim 38, wherein the period is from about 10 minutes to 60 minutes.   40. The method of claim 38, wherein the temperature reaches about 44 to 47 degrees Celsius.   40. The method of claim 38, wherein the drug is a topical drug.   40. The method of claim 38, wherein the drug is a systemic drug.

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