CN102697593B - Device for treating meibomian glands - Google Patents

Abstract

In an implementation scheme conforming to the invention, a method for treating meibomian glands (10) of a mammal comprises the steps: adjusted heat (104) is applied to eyelids including the meibomian glands so as to clear gland bodies, wherein the heat can enable blockages in the meibomian glands to be melted and enable the temperature of blockages to be in a fluid or suspension (melted) state, and the heat is maintained for a period of time so as to enable the blockages to be melted sufficiently; mechanical treatment of the gland bodies can be performed to enable fluid to be extruded out of the gland bodies (108), wherein the treatment is performed during the period of time or after the period of time when the blockages are still in a fluid state; and follow-up drug treatment can be performed to the gland bodies by using a drug (for local use or whole-body use) (112) to assist and maintain lipid to flow out of the gland bodies appropriately. The abstract is not be deemed to be limited because that other implementation schemes can deviate from characteristics described in the abstract.

Description

The therapy equipment of tarsal glands

The treatment of the application's to be the applying date be tarsal glands, application number be 200780039253.8, the divisional application of application for a patent for invention that denomination of invention is identical with the present invention.

The RELATED APPLICATION of pertinent literature

The application is that Korb etc. submitted on May 15th, 2006, be entitled as the U.S. Patent Application No. 11/434 of " method and apparatus for the treatment of meibomian gland dysfunction ", the part continuation application of 054, the U.S. Provisional Application submitted in last application requirement on July 18th, 2005 number 60/700, the priority of 233, the application or Grenon etc. submitted on May 15th, 2006, be entitled as the U.S. Patent Application No. 11/434 of " method and apparatus using the medium treatment gland dysfunction of heating ", the part continuation application of 033, and be that Korb etc. submitted on May 15th, 2006, be entitled as the U.S. Patent Application No. 11/434 of " method and apparatus for the treatment of gland dysfunction ", the continuation-in-part application of 446, wherein each section of full text is incorporated into herein by reference.

Copyright statement

The disclosed part of this patent document comprises material protected by copyright.The imitate true copy (facsimile reproduction) of copyright owner to patent document or patent disclosure is had no objection, because seem in patent and Trademark Office patent file or record, but other all rights outside All rights are reserved.

Invention field

The present invention relates generally to the treatment of mammal eye.More specifically, the present invention relates to by use heating with melt some obturator (or melted join forms material of solids of obturator), mechanism with clear up obturator and once obturator the cleaned multiple combination of Drug therapy that uses obstruction of tarsal glands is treated.

Background of invention

Human body contains many bodies of gland, comprises the mammary gland in the lachrymal gland of eye and tarsal glands, the sebaceous gland of face and oxter or hair-sebum hair gland and breast.Due to the age, stimulation, environmental aspect, cell debris, inflammation, hormone imbalances and other, can dysfunction be there is in these bodies of gland.It is limited or interrupt that a common disease state of eyelid body of gland is that the fluid caused due to obturator flows out body of gland naturally.

In the eye of people, the tear film covering eye table forms by three layers.The rete malpighii that the innermost layer contacted with eye table is made up of many mucin.The composition most intermediate layer of tear film is water layer, and thin (being less than 250nm) layer that outermost layer is made up of many lipids being known as " eyelid fat (meibum) " or " sebum ".Sebum, by specialized sebaceous-type body of gland (therefore, use " sebum " describe this secretion) Meibomian gland secretion of expansion being arranged in upper palpebra inferior, by the hole specially making lipid secretions flow to margo palpebrae, thus forms the lipid layer of tear film.Typical upper eyelid has about 25 tarsal glandss, and palpebra inferior has about 20 tarsal glandss slightly larger than the tarsal glands being positioned at upper eyelid.Tarsal glands comprises the multiple capsule sample acinus of main central canal secretions being flowed into body of gland.Then make secretions pass through by presumption discharge in sebum the smooth muscle tissue that helps out and Li Ao Lang Shi (Riolan) flesh around hole.Meibomian gland orifices open in the eyelid being called mucocutaneous connection of margo palpebrae the junction of mucosa and external skin and around.

Particularly, as set forth in above patent application, each tarsal glands has straight long central canal, its on the inner surface of pipeline by four layers of epithelial layer lining.Along the length of central canal, there is multiple laterally projecting cystic structures being called acinus, produce glandular secretion thing herein.The liner of each acinus is different from main central canal, and wherein these special cells provide the secretions of tarsal glands.Secretions flow to pipeline from each acinus.Determine although still indefinite, seem to there is valve system between each acinus and central canal to be detained secretions until when needing, now secretions is drained into central canal.Then meibomian secretion be stored in central canal and discharged by the hole on each body of gland in margo palpebrae.Nictation and be considered to the main mechanism that open hole discharges from tarsal glands to make secretions around the squeezing action of Lang Shi (Riolan) flesh difficult to understand in tarsal glands.

Upwards stage of nictation causes upper eyelid to be pulled upwardly a slice by the lipid of Meibomian gland secretion and to cross other of tear film two-layer, thus forms the protective coating of a class restriction lower floor evaporation rate.Thus, should see, the incorrect amount of defective lipid layer or such lipid can cause the acceleration of water layer to be evaporated, then causes the symptom being collectively referred to as " xerophthalmia ", such as itch, calcination, stimulation and drying.

Dry eye states has a lot of cause of disease.The common cause of common dry eye states is that wherein body of gland gets clogged or the obstacle of obturation, is commonly referred to " meibomian gland dysfunction " (MGD).As used in this article, term " obturation " and " obstruction ", when they refer to meibomian gland dysfunction, be defined as partially or completely obstruction or the blocking of tarsal glands or its any ingredient, there is solid, the secretions of half-solid or stiff condensation and/or stopper, cause secreting limited or more particularly reduce or stop.Also along with reducing or limited secretion, because situation tarsal glands that is inaccessible or that block can sustain damage, because micro-yellow indicates possible Infection Status, damaged by other, the lipid protective film of the protectiveness of generation is like this insufficient.

Meibomitis, tarsal glands cause its handicapped inflammation, usually along with blepharitis (inflammation of eyelid).With meibomitis, maybe can there is meibomian gland dysfunction, and there is no obvious lid inflammation in meibomian gland dysfunction.Meibomian gland dysfunction is usually the result of keratotic obstructions, it partially or completely blocks the central canal (conduit) of meibomian gland orifices and/or body of gland, or possibly, the connection of acinus or acini valves (assuming that their necessary beings) or acinus and central canal.Such obturator makes the secretory function sustain damage of single tarsal glands.More specifically, these keratotic obstructions can comprise the combination of antibacterial, sebaceous ground substance, death and/or Exfoliative cells, see Korb etc., meibomian gland dysfunction and contact lenses do not tolerate (Meibomian Gland Dysfunction and Contact Lens Intolerance), ophthalmology association magazine (Journal of the Optometric Association) the 51st volume, 3rd phase, (1980), 243-251 page.When by inspecting outer eyelid and obviously finding meibomitis, meibomian gland dysfunction can be not obvious, even be also like this when checking with the slit lamp biomicroscope of enlargement ratio, because can not have Exterior Sign, or Exterior Sign can be small in not being noted.Do not have the Exterior Sign of the meibomian gland dysfunction of obvious lid inflammation can be limited to the slight change of meibomian gland orifices, epithelial cell on aperture undue growth and to make the aperture of body of gland diminish (pouting) as the condensed material of obturator.In the serious meibomian gland dysfunction not having obvious lid inflammation, change can be significant, comprises the margo palpebrae of jagged or waveform, orifice recession and more significantly the undue growth of epithelial cell on aperture and aperture diminish.

Betiding the Hormone change in menopause, and the change of particularly estrogen level, can cause being thickened by the oiliness secretions of Meibomian gland secretion due to the obstruction of gland orifice.Further, the reduction of estrogen level also can make the fertile condition of staphylococcus strengthen.This can cause antibacterial to travel to body of gland, thus causes secreting rate to decline.

When making secretions when the existence due to obturator from the restricted in flow of tarsal glands, the cell observed on margo palpebrae covers with gland orifice and therefore also limits sebum flow and dry eye condition is worsened.Can cause that meibomian gland dysfunction or other factor that meibomian gland dysfunction is worsened comprise the age, obstacle of twinkling, activity use computer, contact lens wear and health with such as injuring normal blink, make to apply some make up, or Other diseases, particularly diabetes.

The state of single tarsal glands can be change, from the optimum state producing the meibomian fluid clarified; To light or moderate meibomian gland dysfunction, wherein produce milky fluid or dense or creamy secretions; To total blockage, wherein not can be observed the secretions of any kind (see Korb etc., " treatment meibomian gland dysfunction after increase Tear Film Lipid Layer Thickness (Increase in Tear Film Lipid Layer Thickness Following Treatment of Meibomian Gland Dysfunction ", lachrymal gland body of gland, tear film and dry eye syndrome (Lacrimal Gland, Tear Film, and Dry Eye Syndromes), 293-298 page, D.A.Sullivan writes, Plenum publishing house, New York (1994)).The significant chemical change of meibomian gland secretions produces together with meibomian gland dysfunction, thus the tear film component of natural generation changes, and ophthalmic diseases being usually known as " xerophthalmia " occurs successively for it.

When tear film being used as single entities and its all each layer is all important, there is from the lipid layer of Meibomian gland secretion the meaning of particular importance because its function be slow down lower floor evaporation and blink time lubrication eyelid to prevent xerophthalmia.

Thus, in order to summarize, the anti-arresting lacrimation film evaporation of Meibomian gland secretion of mammal (e.g., people) eyelid and the oil of lubrication eye and eyelid.These bodies of gland can become blocking or inaccessible by causing so-called " dry eye syndrome " number of mechanisms.Although be not only reason, meibomian gland dysfunction (MGD) is known is the main cause of dry eye syndrome.This obstacle for feature, forms the lipid layer of tear film to prevent normal lipid secretions from tarsal glands flowing with certain obstruction among tarsal glands or its surface.

Such secretions plays a part the evaporation of anti-arresting lacrimation film and lubricates eye and eyelid, and therefore, their shortage can cause dry eye syndrome.In the main thoroughfare of body of gland that can form stenosis or occlusion, or may comprise the path from acinus to main pipe in other position, the obturator of tarsal glands or obturator can be present in or cover the aperture of body of gland.

Set up such theory, namely the acinus of body of gland can have valve in the junction with body of gland main thoroughfare.The present inventor's reasoning, if the work that these valves exist, they are causing also can becoming obstruction in some cases from the flowing minimizing of acinus or locking.These obturators or obturator can have Multiple components.

As the reaction to foregoing teachings, develop multiple therapeutic modality to treat dry eye condition, comprised the eye drop being intended to copy and substitute natural tear film, the medicine being intended to stimulation tear producing cells and be designed to the multiple heater that obstruction of tarsal glands is removed in help.Other technology relates to manual squeezing body of gland.

Eye drop, such as with board eye drop is designed to the healthy tear film pressing close to copy natural generation.But, their application and administration only symptomatic treatment instead of for the potential cause of disease.Further, the use of eye drop is generally used for uncertain time span, thus long-term use can become trouble and costliness.

Also suggestion is had to use medicament forms, such as tetracycline treatment meibomian gland dysfunction, and such treatment Pflugfelder etc. the U.S. Patent Publication US2003/011426 being entitled as " method for the treatment of meibomian gland disease ", be entitled as the U.S. Patent number 6 of " method for the treatment of meibomian gland disease ", 455,583 and be entitled as the application of meibomian gland disease " tetracycline treatment " PCT publication No. WO 99/58131 in open.But this treatment is not proved to be clinical general effective, and it can be unnecessary in without the meibomian gland dysfunction situation caused by body of gland obturator when infecting.As the U.S. Patent number 6 being entitled as " corticosteroid of local preservative free is used for the treatment that xerophthalmia, filamentary keratitis and delay tear remove (or circulation) " at Pflugfelder etc., disclosed in 153607, the use of corticosteroid is also proposed to treat meibomian gland dysfunction.In addition, this treatment proposed seems to treat the symptom of xerophthalmia, and does not treat the potential cause of disease.Have again, as being entitled as the U.S. Patent number 5 of " androgens that application local uses in keratoconjunctivitis or the ophtalmic treatments of TGF-β ", 958,912 and U.S. Patent number 6,107, disclosed in 289, the androgens that application local uses or androgen analog have also been used to treat acute dry eye signs and symptom in keratoconjunctivitis, and these two sections of patents are all issued to Sullivan.

Most of knowledgeable doctor agrees to, it is useful for heating in treatment MGD.According to the characteristic of obturator, heating make actually clogged material melt or loosen, allow body of gland more freely start produce and excretion lipid and other fluid in, thus can be useful.

A kind of form for the thermal therapeutical of meibomian gland dysfunction is disclosed in the european patent application sequence number PCT/GB2003/004782 being entitled as " for the thermoregulator eyelid comprising chemical method ".Disclosed in this patent application, provide a kind of wiper, wherein before use, activate the chemical reagent that will described wiper made to be heated to about 32 DEG C of-Yue 40 DEG C.Then the wiper of heat is applied on eyelid, manual squeezing then can be used to remove the obturator of pipeline.The method does not have its shortcoming, and wherein nonspecific temperature can increase the weight of in eyelid stimulation.

Another method of eyelid and tarsal glands heating is made to be use near infrared ray (NIR).More particularly, two pieces of hard eye sticker sheets are attached on eyeshield by the interpupillary distance according to curee.By elasticity headband, eyeshield is fixed to go up in position.Each paster uses 19 to launch 850nm-1050nm, and peak value is the light emitting diode of the near infrared ray of 940nm.This device produces 10mW/cm after powered up ²energy.Goto, E. etc., by infrared hot compress (Infrared Warm Compression) device to the treatment of non-inflammation obstructive meibomian gland dysfunction, Britain's ophthalmology magazine (British Journal of Ophthalmology), 86th volume (2002), 1403-1407 page.This device is designed to the untouchable infrared heating mask using IR light emitting diode.But, use IR heating mechanism to there is many potential problems.Such as, IR heat can penetrate eyelid and enter cornea, and this is undesirable, and finally can cause cataract or other damage.Further, determined that blocking useful IR mask heater to eliminating does not apply any pressure (although being described to pressue device) to eyelid.In addition, disclose the test that this eyeshield sample is implemented, although be potentially dangerous, this eyeshield produces actual temperature hardly.

The U.S. Patent Publication US2004/0237969 being entitled as " Therapeutic Eye and eyelid cover " covers and is suitable for for a pair to eyelid particularly to tarsal glands releasing heat saturated air, then the protective eye lens that body of gland is heated.The thermal therapeutical of eye is also being published in by Mitra etc. ophthalmology, discuss in the article of being entitled as in (2004) 1-4 pages " normal subjects via the latent heat of new device to the Tear Film Lipid Layer Thickness after tarsus treatment and ocular comfort degree ".

The U.S. Patent Publication US2003/0233135 being entitled as " method and apparatus for prevention and therapy eyelid disease " of Yee attempts to adopt electricity irritation the present invention supposition to clear up inaccessible tarsal glands to the method accelerating helpful inner Lang Shi difficult to understand (Riolan) flesh of Meibomian gland secretion.

The summary of some embodiment

An object of some embodiment conformed to the present invention is, provides the method for the treatment of mammalian eyelids.

Another object of some embodiment conformed to the present invention is, Therapeutic Method is provided, first described method causes lipid from the tarsal glands flowing of eyelid above and/or under simple eye or eyes, to help the obturator removing some type that can be present in tarsal glands or around it, assist maintain the flowing of lipid or otherwise assist to promote the lubrication of eye by Drug therapy subsequently.

In the embodiment conformed to the present invention, the method for the treatment of mammalian meibomian glands comprises the temperature extremely enough being melted the obturator in tarsal glands by the temperature applied the eyelid comprising tarsal glands through regulating, thus make obturator be in fluid or suspension (fusing) state, and maintain this temperature a period of time enough to make melt obstructions and to make obturator be in fluid or suspension (fusing) state, to clear up body of gland.Then can carry out mechanical treatment with by liquid extruding body of gland to body of gland, wherein said process is during the described time period or after the described time period, but now obturator carries out under being still in fluid or suspension state.In most cases, this should carry out in about 90 seconds after the described time period terminates.Then can adopting by using medicine (local uses or whole body is used) the follow-up Drug therapy to body of gland, assisting to maintain lipid and suitably flow from body of gland or otherwise assist the lubrication of promotion eye.

According to some embodiment, the described time can be about 10-60 minute, and about 15 minutes generally for slight to moderate MGD case be suitable.In more serious case, it is required that the treatment of 30-45 minute can be, and for very serious case, is up to and thermal therapeutical more than 60 minutes can be needs.These time hypothetical target temperature be 44-47 degree and preferably 45 degree Celsius, and perhaps higher temperature can be shortened a little or be extended a little for lower temperature.Temperature range can 37 degrees Celsius and more than.

In certain embodiments, described mechanical treatment is undertaken by least one applied to eyelid in constant voltage, vibrational energy, mechanical energy, pulse machine stimulation, extruding eyelid, when applying heat to eyelid at the same time, or when applying vibratility stimulation to eyelid, apply heat, sample of being milked by fluid picture from one or more body of gland is extruded simultaneously.

In another embodiment, the method for the treatment of mammalian meibomian glands dysfunction (wherein occlusion blocks is at least partially from the secretions of the natural generation of gland channel orifice outflow) comprises with the selected persistent period with the selected temperature enough making obturator at least partially soften or liquefy, and is applying the thermal source through regulating from gland channel orifice the most nearby; In obturator being still in softening or liquefaction at least partially time, mechanical treatment is carried out to gland channel orifice, to remove in obturator at least partially; Subsequently, with promoting that lipid is from tarsal glands free-flow or the Drug therapy mammal of otherwise assisting the lubrication promoting eye.

In another embodiment, the method for the treatment of mammalian meibomian glands dysfunction (wherein occlusion blocks flow out from gland channel orifice at least partially the secretions of natural generation) comprise with the selected persistent period and selected enough making obturator at least partially loosen, decompose, the temperature of broken, softening or liquefaction, applying the thermal source through regulating the most nearby from gland channel orifice; Using before the effect of thermal source through regulating is reversed, mechanical treatment is carried out to gland channel orifice, to remove in obturator at least partially; Subsequently, with promoting that lipid is from tarsal glands free-flow or the Drug therapy mammal of otherwise assisting the lubrication promoting eye.

Above general introduction is intended to the embodiment set forth illustratively, and it will obtain best understanding in conjunction with following detailed description, and is not intended to limit scope or the implication of appending claims.

The summary of figure

Set forth the exemplary of the organization and method implemented with some together with advantage of target, by with reference to the following detailed description be combined with accompanying drawing by and obtain best understanding, wherein:

Fig. 1 describes the upper and lower eyelid of people of display tarsal glands.

Fig. 2 is the sectional view of illustrative tarsal glands 20.

Fig. 3 is the sectional view of the tarsal glands 20 that several congested areas is described.

Fig. 4 is the figure of the surfaces externally and internally temperature of patient's eyelid when eyelid outer surface is heated to about 45 degrees Celsius.

Fig. 5 is the flow chart describing the therapeutic process conformed to certain embodiments of the invention.

Fig. 6 is the flow chart describing another therapeutic process conformed to certain embodiments of the invention.

Detailed Description Of The Invention

Although the present invention allows that embodiment exists in many different forms, but to scheme to show and by herein, with detailed specific embodiments, present invention is described, it should be understood that, such embodiment the example being considered to principle is disclosed, and be not intended to limit the invention to specific embodiments that is shown and that describe.In the following description, same reference number for several view described figure in identical, similar or corresponding part.

Term as used herein " one " or " one, be defined as one or more.Term as used herein " plural number ", is defined as two or more.Term " another " as used herein, being defined as is at least two or more.Term as used herein " comprises " and/or " having ", is defined as and comprises (i.e. open language).Term as used herein " connection ", is defined as and is associated, although be not directly necessary and be not that mechanism is upper necessary.Term as used herein " program " or " computer program ", be defined as the job sequence being designed for computer system and performing." program " or " computer program " can comprise subprogram, function, program, goal approach in executable application program, target enforcement, applet (applet), servlet (servlet), source code, object code, shared library/loading dynamic base and/or be designed for other job sequence performed in computer system.

Run through " embodiment ", " some embodiment ", " embodiment " or the similar term mentioned in presents, refer to be included at least one embodiment of the present invention in conjunction with concrete feature, structure or the feature described by described embodiment.Thus, the appearance of such phrase or be present in that this description multiple places are in the whole text unnecessary all refers to same embodiment.And concrete feature, structure or feature can unrestrictedly combine in any suitable manner in one or more embodiment.

Term "or" as used herein, is interpreted as comprising or mean any one or any combination.Therefore, " A, B or C " means " following any one: A; B; C; A and B; A and C; B and C; A, B and C ".The exception of this definition will only occur when constitutionally repels mutually in some way when the combination of key element, function, step or action.

As above indication, the Etiological that known meibomian gland dysfunction (MGD) is dry eye syndrome.This disorder is blocked with certain in tarsal glands, and overslaugh normal lipid secretions is feature from flowing through hole and flowing out body of gland to tear film.The obturator of tarsal glands or obturator can be present in the hole of body of gland, and the main thoroughfare of body of gland maybe may be present in other position, comprises the main thoroughfare of the body of gland that can be stenosis or occlusion.Existing theory is thought, the acinus of body of gland can have valve in the junction, main thoroughfare of they and body of gland, and these valves get clogged in some cases and cause reducing from the flowing of acinus or blocking.These obturators or obturator can have Multiple components.

Now, with reference to figure 1, the position of tarsal glands 10 is presented on upper eyelid 12 and palpebra inferior 14 respectively.As in above concise and to the point statement, upper eyelid containing have an appointment 25 tarsal glandss and palpebra inferior containing having an appointment 20 tarsal glandss, significant difference.As shown in the cross-sectional view of the body of gland of in fig. 2 10, each body of gland comprises central canal or passage 18, and secretions flows into the hole 20 wherein also flowing to and open to margo palpebrae from acinus 19, by flowing like this secretions is added to tear film when blinking.Should see, according to the position of present eyelid, varying in size of body of gland, and hole 20 is narrower than central canal 18.

Obstruction composition is different and different by the cause of disease that produces because of it.But, observe in present most of case, obturator by with dead cell, antibacterial, exfoliative cyte and be gathered in exfoliative cyte in keratinization clump, milky fluid, dense combination that is thick or creamy secretions exist, or aforesaid any combination exists with the form of solid, semisolid and stiff.With reference to figure 3, describe the simplification view of the obstruction to body of gland 10 as an example.In this example, the Typical Representative of its necessity of all obstruction of tarsal glands things anything but, as explained above, describe the stopper 24 of solid or half-solid or stiff, it makes the hole 20 of body of gland 10 entirely shut.Another obturator 26 is shown in the junction of an acinus and central canal.As indicated above, this can be the location point of the valve in gland structure, but the embodiment conformed to the present invention should not limit to by the theory of the meibomian gland structure of reality.

Make these bodies of gland return to normal function although proposed some treatment technologies, most of doctor approves that heat is useful in treatment MGD.According to the character of obturator, heat actual make clogged material or in conjunction with solids to form the material melts or useful in loosening of obturator, this makes body of gland start more freely to produce and drain lipid and other fluid.Although have been found that the thermal treatment method described in Background section hereof has many shortcomings, have been found that the heat treatment technics described in copending application cited above is effective and useful.In general, these devices produce temperature (as detected at its outer surface) through regulating by directly contacting with eyelid to eyelid, reaching higher than 37 degrees Celsius, is more preferably about 44-47 degree Celsius, and target temperature is the treatment temperature of 45 degrees Celsius.But, other device be placed near eyelid place can be used with to tarsal glands heat supply.

Observe the external skin surface about 1-2 degree Celsius lower than body temperature of people's eyelid, and have some differences.Temperature is increased at least 37 degree can start to provide response to treatment to more slight MGD case.Have been found that the preferred scope be used for the treatment of is 44-47 degree Celsius, target temperature is 45 degrees Celsius is effective and comfortable for patient.In certain embodiments, at this moment during section or after this time period terminates immediately preferred heating instrument carry out Mechanical energy treatment, to maintain obturator having more fluid state.Any machinery causing mechanical pressure can be adopted to carry out Mechanical energy treatment, include but not limited to vibrate, extrude, mechanical pulsing pressure, extruding and other operation make fluid extrude from body of gland and/or make pipeline or the bore expansion of tarsal glands.Mechanical energy can take any form, applies mechanical pressure by during thermal softening, locking thing or obturator are released body of gland to aid in obturator to tarsal glands.Both made to use much higher temperature (e.g., 50-55 degree Celsius) (or pulsed for short periods), and if particularly eyelid is anaesthetized, in the case, can the treatment of higher temperature used the short time and permanent damage not caused to patient.Usually, higher temperature can be used to be used for shorter time.In addition, temperature and time used should be personalized, its order of severity based on disease and patient tolerance.Have been found that the patient that the shallow patient of the colour of skin is generally dark than the colour of skin can tolerate lower temperature, and the dark patient of the colour of skin tends to show fewer as the inflammation by thermal result.Adjustable treatment time and/or temperature are to solve these difference.Each temperature refers to the temperature in the measurement of eyelid appearance above.

Further, in certain embodiments, when treat to start with lower temperature and along with the time in the past temperature increase time, patient feels more comfortable.Therefore, should temperature be regulated, this adjustment should be explained be intended to eyelid appearance the actual temperature used control in a repeatable fashion and regulate.For heat application, its Temperature Distribution can be constant temperature, maybe can have to tiltedly upper soaring, to gradually falling under tiltedly, peak, paddy, can be pulse, or available various features adjustment etc., but should carry out adjustment to such distribution makes it as repeatably.Also have been found that and regulate temperature can cause the mean temperature higher than constant temperature, and can be useful in some applications.

This temperature can be maintained the treatment cycle (even if it is safe and useful for not yet finding for some patient) of in treatment temperature about 10-60 minute.Have been found that, or at the treatments period or after this of such temperature with controlling, from tarsal glands mechanical presses lipid and other fluid to clear up obturator that is that substantially melted or that be in suspension state (material melts due to together with solid bond).More than application disclose usual to eyelid apply to extrude action with extrude fluid or suspension or other mechanical stimulus from the device-fluid so at present of the motion of the fluid of body of gland comprise cause block or obturation fusing or the material of suspendible.In some cases, only apply the gentle power continued to eyelid and will help extrusion fluid and suspension, and in other cases, simultaneously or mode of vibration can be used immediately after the heating.Be suitable for the object of presents, term " fusing " is interpreted as comprising the state that wherein solids keep being suspended in fluid liquid.

In certain embodiments, the device applying the temperature through regulating to eyelid like this Korb etc. on May 15th, 2006 to submit to, the U.S. Patent Application No. 11/434 that is entitled as the method and apparatus being used for the treatment of meibomian gland dysfunction, 054 and Steve Grenon etc. submits on May 15th, 2006, the U.S. Patent Application No. 11/434 that is entitled as " fusing obstruction of tarsal glands thing ", open in 033, these two sections of documents are incorporated into herein by reference.In certain embodiments, this device utilizes the unit heater of the heating element heater with the heat production when applying the signal of telecommunication.In order to realize by heating element heats to specific temperature range, thermoregulator applies the signal of telecommunication to heating element heater.Unit heater is connected to eyelid to realize applying the temperature through regulating to eyelid in specific temperature range by eyelid interfacing mechanism.

Such device provide through regulate temperature to treating temperature.The hot compress (hot compresses) of the routine described in above background of invention and IR heating mechanism do not provide the heating of regulable control at the temperature for the treatment of, and poorer than being used in the temperature effect through regulating that the device that describes in patent application that is cited above, that be incorporated into herein uses.

In another embodiment disclosed in present patent application, at least one eyelid to patient provides the apparatus of in check heat to have unit heater, and this unit heater has: the heating element heater on the first and second surfaces of heat production when applying the signal of telecommunication; Be connected to the first surface of heating element heater heat to be passed to the fin of eyelid from heating element heater; Be connected to the second surface of heating element heater to reduce the insulator of heat from second surface loss; With the backboard being connected to insulator.In order to realize by heating element heats to specific temperature range, thermoregulator applies the signal of telecommunication to heating element heater.There is provided the protective eye lens being suitable for tying up on patient's head and hiding patient's eyelid with eyeglass, eyeglass place has tapped bore.Thread spindle passes through threaded lenspiece and is connected with the unit heater on backboard, so that by contacting being moved into by unit heater in axle precession hole with eyelid, until realize contacting with eyelid.

Many variations in these embodiments may include, but are not limited to the sensor providing sense temperature and provide temperature information to thermoregulator.In certain embodiments, eyelid interfacing mechanism comprises in order to traveling heater unit is to realize the protective eye lens being connected to unit heater adjustably contacted with eyelid.By threaded connection, protective eye lens is connected to unit heater adjustably, action spiral can be adopted like this to adjust the position of unit heater.In certain embodiments, unit heater has in order to heat is passed to eyelid from heating element heater and is connected to the fin on the surface of heating element heater.Fin can be, such as, and heat conducting rubber parts, conduction of heat silicon cell, containing at least one in the element of encapsulated fluid and solid conductive member.Conduction of heat gel, cream or liquid can be placed between fin and eyelid to strengthen the conduction of heat from fin to eyelid.

In certain embodiments, in order to reduce from heating unit to not being heat loss towards eyelid direction, unit heater can have the insulator being connected to heater element surface.Heat insulator can be the one in non-conduction of heat foam element, non-conduction of heat rubber element and the non-conduction of heat solid-state components in some embodiment.In order to regulate the heat production of heating element heater, thermoregulator can apply the pulsewidth modulation signal of telecommunication to heating element heater, and the pulsewidth modulation signal of telecommunication can produce under the control of control processor.

In certain embodiments, in order to regulate the heat production of heating element heater, thermoregulator can be formed integrated with the switch applying the signal of telecommunication to heating element heater selectivity.The selectivity that the signal of telecommunication can be under control processor controls puts on the electric current of heating element heater and at least one of voltage.In order to match with eyelid, the flexible portion that unit heater can have contact eyelid maybe can have the rigid element contacting eyelid, and wherein rigid element is formed as the shape adapting to eyelid, or their combination.Unit heater can have gluing for directly being sticked to by unit heater on eyelid or by using adhesive tape to tie up at eyelid.

In certain embodiments, user interface permission user sets up at least one in the time and temperature be used for the treatment of.In certain embodiments, there is vibration to stimulate the secretion from tarsal glands to eyelid in vibration machine, wherein vibration machine can have the mechanical energy of amplitude and frequency to eyelid transmission.

The device of other heat production and/or generation pressure is open in patent application cited above, and described patent application is incorporated into herein by reference.

Therefore, in view of the above circumstances, or after thermal therapeutical immediately or during such thermal therapeutical, mechanical treatment can be applied to eyelid, such as, adopt constant force, extruding (e.g., by manual expression or alternate manner), extrude action or vibration, to stimulate from tarsal glands cleaning fluid or suspension.If carry out mechanical treatment after thermal therapeutical, should carry out immediately when the clogged material of tarsal glands is thereafter in molten state.

With reference now to Fig. 4, the eyelid inner surface of secondary description when the constant-heat source of about 45 degrees Celsius being applied to tested patients as an example and a figure for eyelid outer surface.Should indicate, blood circulation attempts to regulate the temperature of eyelid, and increases due to the application blood flow of heat.For this patient, spend and within about 4 minutes, make the outer surface of eyelid reach about 45 degrees Celsius, and eyelid inner surface never reached that this temperature-the chances are because the heat regulatory mechanisms of health in action.Therefore, if use 45 degree of constant-heat sources, can spend and made stabilize eyelid temperature at least about 4 minutes and reach treatment temperature.From this figure also it is noted that, when removing thermal source from eyelid, temperature very rapidly drops to body temperature.In fact in all cases, this temperature will decline in 2-3 minute, and more commonly, the eyelid temperature of patient was declined and only needs about 30 seconds to 90 seconds.In this example, in removal heating back 30 seconds, temperature declines very fast.Within this short time, the obturator melted of some or all can solidify again.Therefore, if manual expression techniques must be carried out after applying heat, then manual expression should be caught up with immediately, or carried out in about 90 seconds-and shorter interval is preferred, as, in 30 seconds, in any case or, carried out before the effect using the thermal source through regulating is reversed, the removal at least partially in such obturator.Can understand from this figure, if manual expression does not carry out within the extremely short time, then use hot compress can be substantially invalid in first technology.In addition, if dressing cooling is lower than treatment level before manual expression, then they only may provide few benefit to the patient suffering from firm obturator misery.

Have been found that great majority for the problem of the medical treatment regime of dry eye syndrome are, when disease relates to body of gland obstruction, medicine can not have an impact to MGD.That is, known at present Drug therapy can not remove the obstruction of tarsal glands simply to allow the flowing of lipid.And antibiotic therapy, steroid therapy or other medicines therapy can be used for the xerophthalmia caused by other reason, have been found that they are invalid (or providing temporary remission at the most) when relating to body of gland and blocking.Although many medicines produce at the lipid of promotion tarsal glands and can be useful in flowing, it is invalid that such lipid produces, and if secretions can not discharge body of gland, can resist it and produce.In fact, promote that lipid produces more meibomian difficulties and the inflammation that can cause body of gland.

Other medicines can help lend some impetus to the lubricating function that tear produces or otherwise contributes to eye by promoting to improve tear film.If be used alone, such treatment can be invalid or only partly effective, but use after cleaning tarsal glands, and the generation of tear film all the components can be made to recover normal or normally close.Therefore, many medicines can be suitable for increasing further tear film, and recover more normal function once tarsal glands, can be to be highly profitable.

Therefore, made the flowing of tarsal glands recover once pass through heat with manual process (e.g., treatments period or compressing afterwards, vibration, pulse, manual expression etc.), can be useful to maintain lipid from body of gland outflow with the treatment of multi-medicament.Therefore, with reference to figure 5, describe therapeutic scheme, the program starts from 100, after this, uses the temperature of control in 104 to eyelid, such as quotes from above and is incorporated into the temperature that the multiple apparatus that describes in patent application herein produces by reference.Preferred temperature is higher than 37 degrees Celsius, and preferred heating range is about 44-47 degree Celsius, and target is 45 degrees Celsius.But the higher Celsius temperature of shorter time will provide treatment benefit, possible side effect will be the slight skin burn not causing lasting damage.Lower than this temperature range, treatment trends towards less effect or invalid.Temperature higher than this scope can cause the serious discomfort of patient, injures eyelid and may injure eyes.During higher temperature within the scope of this, patient can feel this temperature, and some is uncomfortable, but treatment time can reduce, and available anesthetis alleviates described discomfort.Lower temperature within the scope of this is effective, but the heating cycle that general cost is longer.

By rule of thumb, for many slightly to patient's starting point of moderate MGD, in relative constant temperature, 45 degree of 15 minutes patients generally do not have unsuitable discomfort.According to the tolerance degree of the order of severity of MGD disease, temperature, anesthetis used and patient, spendable time range is about 10-60 minute or even more.In an experiment, use the time more than 1 hour and there is no obvious untoward reaction.

Once thermal therapeutical completes (and/or during thermal therapeutical), can apply with the mechanical force of any mode of the mechanical system of above-mentioned discussion in 108, to extrude fluid or suspension when obturator is in molten state from tarsal glands.When use extrudes body of gland, preferably to any apparatus heating used in extrusion process, so that apply to body of gland when extruding simultaneously or assist to maintain temperature.

Although manual expression body of gland can be painful, and due to the variation of hand control and/or operation, invasive inconsistent with result when being used alone, although with because need doctor to extrude body of gland, the method of this treatment MGD also can be very uncomfortable to patient, but this technology provable is useful as the step in the method for choice for use in Complex cases.Have an appointment between upper and lower eyelid 45-50 body of gland, therefore, it is very time-consuming for extruding each body of gland, and therefore, is inefficient and be uncomfortable be difficult to tolerance to patient for doctor.But as indicated, associating automatic extrusion device is crossed aperture with the body of gland of assisting to clear up further Severe blockage with enhanced flow and is flowed out body of gland to the lipid proper flow of tear film, can be useful.After thermal therapeutical, if compared to being used alone, normally remarkably more effectively and less causing patient uncomfortable from the body of gland extruding secretions blocked and obtaining better result.As front indicated, when applying extruding body of gland method, be preferred heating any apparatus used in extrusion process, so that when extruding, temperature applied to body of gland simultaneously or assist to maintain temperature.

In 104 and 108, once flow from tarsal glands cleaning obturator and other foreign substance with recovery lipid, in order to make, glandular inflammation is minimum, cleaning is infected, prevent further locking, lipid is thinned out, promote tear generation, increase the composition of tear film or promote lipid free-flow or strengthen other pharmacological modality any of eyes lubrication, in 112, any one treatment tarsal glands of available multi-medicament (or local is used or whole body is used).Drug therapy can be carried out or short time (e.g., to clear up infection or inflammatory disorders) or continue to carry out to treat (e.g., as with making lipid thin out, reduce inflammation or treat the medicine of other form of dry eye syndrome).This process terminates 116.

Many medicines have been proposed for treatment dry eye syndrome, and wherein any medicament obturator can be effective or more effective in cleaning tarsal glands.More spendable medicines include, but are not limited to: antibiotic such as local with or oral tetracycline and the tetracycline modified through chemical method, testosterone, local with or oral corticosteroids, topical androgens or androgen analog, Ω 3 fatty acid cpds such as fish oil, Placenta extract (laennec), the enzyme promoting lipid to produce, stimulate promote the medicine of the generation of the enzyme that lipid produces and as increase sercretogogue that Meibomian gland secretion or other tear component secrete any medicine.Existing report, androgen and androgen analog and TGF-β with increasing Meibomian gland secretion, substituting or promote the generation medicine of any tear component, and may have other medicines many as sercretogogue.These compounds are the illustrative of suitable medicine, but professional and technical personnel in the field should be realized that, based on considering what the present invention instructed, can apply the compound that other has pharmacological action.Also it is noted that, can multiple form be comprised in the reason causing dry eye syndrome, but only a kind of mode is treated and can not be caused full resolution.Therefore, make to recover normal or close to normally can be the part of only solution-make tear film recover normally with the alternate manner of medicine disease therapy or various ways from the flowing of the lipid of tarsal glands.But when involving significant MG dysfunction, the treatment of alone alternate manner is perhaps less satisfactory.

Composition graphs 6 describes the mutation of above treatment, in 130, thereafter in 104, as in first Therapeutic Method, the temperature through regulation and control is used, such as by quoting and be incorporated into by reference in patent application herein the temperature describing multiple apparatus and produce above to eyelid.The preferred scope of such temperature is about 44-47 degree Celsius again, and target is 45 degrees Celsius.Further, spendable time range is about 10-60 minute and more, this depends on the order of severity of disease, treatment temperature and patient tolerance.

In this embodiment, during thermal therapeutical, in 138, can any mechanical system of above-mentioned discussion, comprise those quote and be incorporated into mechanical system herein by reference, when obturator is in liquid or suspension state during applying temperature, apply mechanical pressure, to extrude fluid or suspension from tarsal glands.

In 138, according to patient, temperature is combined to the reaction of mechanical pressure, after removal temperature, in 142, other power can be applied immediately simultaneously.In the case, in extruding or in the applied force time as described, temperature being maintained, is also preferred.That is, during extruding, being in liquid or suspension state to any probe used or the heating of other utensil to help maintaining obturator, is preferred.Can manually apply such power, by In the view of suitable obturator residual position extruding eyelid, if or available words can adopt automation method.

Once in 104,138 and 142, from some or all of tarsal glandss cleaning obturator and other foreign substance, in order to make, glandular inflammation is minimum, cleaning is infected, prevents further locking, lipid is thinned out, as front, in 112, available multi-medicament (local with or whole body with), or promote lipid free-flow or or alternate manner promote that tear film improves other pharmacological modality any.As specified, Drug therapy can be carried out or short time (e.g., to clear up infection or inflammatory disorders) or continue to carry out to treat (e.g., as with making lipid thin out, improving the medicine of tear component or minimizing inflammation).This process terminates 150.

Above method, no matter the method whether comprising Fig. 5 or Fig. 6, when causing or maintains the suitable flowing from tarsal glands as needed, can repeat at interval or exchange use.For some patients, in order to keep lipid from the flowing of tarsal glands, such treatment or its part periodically can be repeated.

Thus, according to some embodiment conformed to the present invention, the method for the treatment of mammalian meibomian glands comprises by applying temperature through regulating to the eyelid comprising tarsal glands clear up body of gland, and described temperature reaches the temperature of the obturator in enough fusing tarsal glandss and maintains this temperature a period of time enough to make melt obstructions and make obturator be in fluid or suspension (fusing) state.Then can carry out mechanical treatment so that fluid or suspension are extruded body of gland to body of gland, wherein said mechanical treatment between the described time or after the described time but now obturator carries out under being still in molten state.This process is strengthened with the therapy equipment of holding temperature and obstructive material molten state for applying power by heating.Then can adopting the Subsequent pharmacological treatment to body of gland by using medicine (local uses or whole body is used), suitably flowing from body of gland to assist maintaining lipid.

According to some embodiment, the described time can be about 10-60 minute, and about 15 minutes generally for slight be suitable to moderate cases.Temperature should higher than 37 degrees Celsius and the preferred scope of eyelid hull-skin temperature is about 44-47 degree Celsius, and target is 45 degrees Celsius, has been found that to patient it is effective and comfortable.In certain embodiments, after the heating as quickly as possible, preferably within about 30-90 second, carry out mechanical treatment, so in extrusion process, obturator will be held in molten state.In other embodiment, apply temperature at the same time, or when applying vibratility stimulation to eyelid, when applying temperature simultaneously, by application constant voltage, extruding, at least one extruded from one or more body of gland as sample of milking fluid or suspension, carry out mechanical treatment.Based on considering that the present invention instructs, professional and technical personnel in the field by remember many variations and alternate embodiment.

Although described some illustrative embodiment, be apparent that, many alternative, revise, change and variation, for professional and technical personnel in the field, will become clear according to description before.

Claims (2)

1. providing the temperature through regulating to be used for the treatment of a device for mammalian eyelids, comprising:

Unit heater, this unit has the heating element heater of heat production when applying the signal of telecommunication to it;

Thermoregulator, described thermoregulator applies the signal of telecommunication to realize heating element heats to specific temperature range to heating element heater; With

Eyelid interfacing mechanism, this eyelid interfacing mechanism makes unit heater contact to realize to make in specific temperature range eyelid to reach temperature through regulating with eyelid.

2. the device of claim 1, wherein said heating element heater is stratie.

3. the device of claim 1, its sensor also comprising sense temperature and temperature information is provided to thermoregulator.

4. the device of claim 1, wherein said eyelid interfacing mechanism comprises protective eye lens, and described protective eye lens is connected to unit heater adjustably so that traveling heater unit is to realize the contact of itself and eyelid.

5. the device of claim 1, wherein said unit heater also comprises in order to heat is passed to eyelid from heating element heater and is connected to the fin on the surface of heating element heater.

6. the device of claim 1, wherein said unit heater also comprises the insulator that is connected to heater element surface to reduce from heating unit to the non-heat loss towards eyelid direction.

7. the device of claim 1, wherein said thermoregulator can also comprise to the heating element heater selectivity applying signal of telecommunication to regulate the switch of its heat production.

8. the device of claim 1, wherein said unit heater has the flexible portion of contact eyelid to match with eyelid.

9. the device of claim 1, wherein said unit heater has the rigid element of contact eyelid, and wherein rigid element is formed as the shape adapting to eyelid.

10. the device of claim 1, wherein said unit heater also comprises gluing for unit heater is directly sticked to eyelid.

The device of 11. claim 1, at least one wherein setting in unit heater and thermoregulator applies through the heat one section of the adjustment selected time the tarsal glands in eyelid in selected temperature, enough to make the obturator at least partially in tarsal glands soften or liquefaction.

The device of 12. claim 11, it also comprises mechanical energy generator, and this generator is positioned at the hole of obturator by the tarsal glands at tarsal glands top of eyelid meibomian gland channel with extruding to eyelid generation power.

The device of 13. claim 12, wherein while device applies heat to eyelid, mechanical energy generator produces power on eyelid.

The device of 14. claim 12, wherein said mechanical energy generator produces power and applies to milk work in order to extrude secretions from tarsal glands to eyelid.

The device of 15. claim 12, wherein said mechanical energy generator produces power and applies effect of vibration to extrude secretions from tarsal glands to eyelid.

The device of 16. claim 12, wherein said mechanical energy generator produces power and applies squeezing action to extrude secretions from tarsal glands to eyelid.

The device of 17. claim 12, wherein said mechanical energy generator produces power and applies fluctuation pressure to extrude secretions from tarsal glands to eyelid.

The device of 18. claim 12, wherein said mechanical energy generator produces power and applies constant voltage to extrude secretions from tarsal glands to eyelid.

The device of 19. claim 12, wherein mechanical energy generator produces power to extrude the hole of obturator by tarsal glands of the softening or liquefaction in the meibomian gland channel of tarsal glands.

The device of 20. claim 1, wherein selected temperature range is greater than the temperature range of 37 degrees Celsius.

The device of 21. claim 1, wherein selected temperature range is the temperature range between 44-47 degree Celsius.

The device of 22. claim 1, wherein selected temperature range is the temperature range near about 45 degrees Celsius.

The device of 23. claim 1, it closes the timer of the signal of telecommunication to heating element heater after being also included in the selected processing time.

The device of 24. claim 22, the wherein selected processing time is greater than 10 minutes.

The device of 25. claim 1, it also comprises pressure transducer, and described pressure transducer detects pressure unit heater being applied to eyelid.

The device of 26. claim 1, wherein a part for eyelid interfacing mechanism is disposable.

The device of 27. claim 1, it also comprises regulating measure for setting amount of pressure unit heater being applied to eyelid.

The device of 28. claim 1, wherein eyelid interfacing mechanism is also arranged to be connected to contact eyelid with unit heater, with realize make in specific temperature range eyelid reach through regulate temperature, the obturator of meibomian gland channel is positioned at fusing, and wherein eyelid interfacing mechanism is also arranged to be connected to contact eyelid with unit heater, to apply the power of obturator by the hole of tarsal glands of the fusing being enough to extrude in meibomian gland channel to eyelid.