EP2101697A1 - Traitement des glandes de meibomius - Google Patents

Traitement des glandes de meibomius

Info

Publication number
EP2101697A1
EP2101697A1 EP07716448A EP07716448A EP2101697A1 EP 2101697 A1 EP2101697 A1 EP 2101697A1 EP 07716448 A EP07716448 A EP 07716448A EP 07716448 A EP07716448 A EP 07716448A EP 2101697 A1 EP2101697 A1 EP 2101697A1
Authority
EP
European Patent Office
Prior art keywords
glands
pharmacological agent
treating
meibomian
eyelid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07716448A
Other languages
German (de)
English (en)
Other versions
EP2101697A4 (fr
Inventor
Donald R. Korb
Timothy R. Willis
Stephen M. Grenon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TearScience Inc
Original Assignee
TearScience Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by TearScience Inc filed Critical TearScience Inc
Publication of EP2101697A1 publication Critical patent/EP2101697A1/fr
Publication of EP2101697A4 publication Critical patent/EP2101697A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/02—Compresses or poultices for effecting heating or cooling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F2007/0001—Body part
    • A61F2007/0002—Head or parts thereof
    • A61F2007/0004—Eyes or part of the face surrounding the eyes

Definitions

  • This invention relates generally to treatment of mammalian eyes. More particularly, this invention relates treatments of obstruction of meibomian glands by use of various combinations of heat to melt certain obstructions (or melt material binding solid particles forming an obstruction), mechanical action to clear the obstruction and pharmaceutical treatment once the obstruction has been cleared.
  • the human body contains a number of glands including the lacrimal and meibomian glands of the eye, the sebaceous or pilo-sebaceous hair glands on the face and underarms, and the mammary glands in the breasts. These glands may malfunction due to age, irritation, environmental conditions, cellular debris, inflammation, hormonal imbalance and other causes.
  • One common disease state of the eyelid glands is the restriction or stoppage of the natural flow of fluid out of the gland caused by an obstruction.
  • the tear film covering the ocular surfaces is composed of three layers.
  • the innermost layer in contact with the ocular surface is the mucus layer comprised of many mucins.
  • the middle layer comprising the bulk of the tear film is the aqueous layer, and the outermost layer is a thin (less than 250nm) layer comprised of many lipids known as "meibum” or "sebum".
  • the sebum is secreted by the meibomian glands, enlarged specialized sebaceous-type glands (hence, the use of "sebum” to describe the secretion) located within both the upper and lower eye lids, with orifices designed to discharge the lipid secretions onto the lid margins, thus forming the lipid layer of the tear film.
  • the typical upper eyelid has about 25 meibomian glands and the lower eyelid has about 20 meibomian glands, which are somewhat larger than those located in the upper Hd.
  • the meibomian gland comprises various sac-like acini which discharge the secretion into the main central duct of the gland.
  • the secretion then passes into the orifices which are surrounded by smooth muscle tissue and the muscle of Riolan which are presumed to aid in the expression of sebum.
  • the meibomian gland orifices open onto the lid margin at and around the junction of the inner mucous membrane and the outer skin of the eyelids termed the mucocutaneous junction.
  • each meibomian gland has a straight long central duct lined with four epithelial layers on the inner surface of the duct.
  • acini where the secretion of the gland is manufactured.
  • the inner lining of each acinus differs from the main central duct in that these specialized cells provide the secretions of the meibomian gland.
  • the secretions flow from each acinus to the duct. While it has not been established with certainty, there appears to be a valve system between each acinus and the central duct to retain the secretion until it is required, at which time it is discharged in to the central duct.
  • the meibomian secretion is then stored in the central duct and is released through the orifice of each gland onto the lid margin.
  • Blinking and the squeezing action of the muscle of Riolan surrounding the meibomian glands are thought to be the primary mechanism to open the orifice for the release of secretion from the meibomian gland.
  • the upward phase of blinking causes the upper lid to pull a sheet of the lipids secreted by the meibomian glands upward and over the other two layers of the tear film, thus forming a type of protective coating which limits the rate at which the underlying layers evaporate.
  • a defective lipid layer or an incorrect quantity of such lipids can result in accelerated evaporation of the aqueous layer which, in turn, causes symptoms such as itchiness, burning, irritation, and dryness, which are collectively referred to as "dry eye".
  • Dry eye states have many etiologies.
  • a common cause of common dry eye states is a disorder where the glands are obstructed or occluded, usually referred to as "meibomian gland dysfunction" (MGD).
  • MMD meibomian gland dysfunction
  • occluded and obstruction as they relate to meibomian gland dysfunction are defined as partially or completely blocked or plugged meibomian glands, or any component thereof, having a solid, semi-solid or thickened congealed secretion and/or plug, leading to a compromise, or more specifically, a decrease or cessation of secretion.
  • the meibomian gland may be compromised by the occluded or obstructive condition as evidenced by a yellowish color indicating a possible infection state, or may be otherwise compromised so that the resulting protective lipid protective film is not adequate.
  • Meibomitis an inflammation of the meibomian glands leading to their dysfunction, is usually accompanied by blepharitis (inflammation of the lids). Meibomian gland dysfunction may accompany meibomitis, or meibomian gland dysfunction may be present without obvious lid inflammation. Meibomian gland dysfunction is frequently the result of keratotic obstructions which partially or completely block the meibomian gland orifices and/or the central duct (canal) of the gland, or possibly the acini or acini valves (assuming they do in fact exist) or the acini's junction with the central duct. Such obstructions compromise the secretory functions of the individual meibomian glands.
  • these keratotic obstructions can comprise combination of bacteria, sebaceous ground substance, dead, and/or desquamated epithelial cells, see, Korb et al., Meibomian Gland Dysfunction and Contact Lens Intolerance, Journal of the Optonietric Association, Vol. 51, Number 3, (1980), pp. 243-251. While meibomitis is obvious by inspection of the external lids, meibomian gland dysfunction may not be obvious even when examined with the magnification of the slit-lamp biomicroscope, since there may not be external signs, or the external signs may be so minimal that they are overlooked.
  • the external signs of meibomian gland dysfunction without obvious lid inflammation may be limited to subtle alterations of the meibomian gland orifices, overgrowth of epithelium over the orifices, and pouting of the orifices of the glands with congealed material acting as obstructions.
  • the changes may be obvious, including serrated or undulated lid margins, orifice recession and more obvious overgrowth of epithelium over the orifices, and pouting of the orifices.
  • Hormonal changes which occur during menopause, and particularly changing estrogen levels, can result in thickening of the oils secreted by the meibomian glands which results in clogged gland orifices. Further, decreased estrogen levels may also enhance conditions under which staphylococcal bacteria can proliferate. This can cause migration of the bacteria into the glands, thus resulting in a decreased secretion rate.
  • meibomian gland dysfunction When the flow of secretions from the meibomian gland is restricted due to the existence of an obstruction, cells on the eyelid margin have been observed to grow over the gland orifice thus further restricting sebum flow and exacerbating the dry eye condition. Additional factors which may cause or exacerbate meibomian gland dysfunction include, age, disorders of blinking, activities such as computer use which compromise normal blinking, contact lens wear and hygiene, cosmetic use, or other illness, particularly diabetes.
  • the state of an individual meibomian gland can vary from optimal, where clear meibomian fluid is produced; to mild or moderate meibomian gland dysfunction where milky fluid or inspissated or creamy secretion is produced; to total blockage where no secretion of any sort can be obtained (see Korb, et al., "Increase in Tear Film Lipid Layer Thickness Following Treatment of Meibomian Gland Dysfunction", Lacrimal Gland, tear Film, and Dry Eye Syndromes, pp. 293-298, Edited by D.A. Sullivan, Plenum Press, New York (1994)).
  • Significant chemical changes of the meibomian gland secretions occur with meibomian gland dysfunction and consequently, the composition of the naturally occurring tear film is altered, which in turn, contributes to ocular disease which is generally known as "dry eye”.
  • the lipid layer which is secreted from the meibomian glands, is of particular significance as it functions to slow the evaporation of the underlying layers and to lubricate the eyelid during blinking which prevents dry eye.
  • the meibomian glands of mammalian (e.g., human) eyelids secrete oils that prevent evaporation of the tear film and provide lubrication to the eye and eyelids. These glands can become blocked or plugged by various mechanisms leading to so- called "dry eye syndrome". While not the only cause, meibomian gland dysfunction (MGD) is known to be a major cause of dry eye syndrome.
  • MMD meibomian gland dysfunction
  • the disorder is characterized by a blockage of some sort within the meibomian glands or at their surface preventing normal lipid secretions from flowing from the meibomian glands to form the lipid layer of the tear film.
  • Such secretions serve to prevent evaporation of the tear film and lubricate the eye and eyelids, hence their absence can cause dry eye syndrome.
  • Obstructions or occlusions of the meibomian glands may be present over or at the orifice of the gland, in the main channel of the gland which may be narrowed or blocked, or possibly in other locations including the passages from the acini to the main channel.
  • the acini of the glands may have valves at their junction with the main channel of the gland.
  • the inventors theorize that if these valves exist, they may also become obstructed in some instances leading to reduced or blocked flow from the acini. These obstructions or occlusions may have various compositions.
  • Eye drops such as Refresh ® , Soothe ® and Systane ® brand eye drops are designed to closely replicate the naturally occurring healthy tear film. However, their use and administration is merely a treatment of symptoms and not of the underlying cause. Further, the use of drops is generally for an indefinite length of time and consequently, extended use can become burdensome and costly.
  • corticosteroids have also been proposed to treat meibomian gland dysfunction as disclosed in United States Patent No. 6,153607 titled "Non-preserved Topical Corticosteroid for Treatment of Dry Eye, filamentary Keratitis, and Delayed Tear Clearance (or Turnover) to Pflugfelder et al. Again, this proposed treatment appears to treat the symptom of dry eye, as opposed to treatment of the underlying cause. Additionally, the use of topically applied androgens or androgen analogues have also been used to treat acute dry eye signs and symptoms in Keratoconjuctivitis Sicca as disclosed in United States Patent No. 5,958,912 and United States Patent No. 6,107,289 both titled "Ocular Therapy in Keratoconjunctivitis Sicca Using Topically Applied Androgens or TGF- ⁇ " and both issued to Sullivan.
  • heat is beneficial in treating MGD. Depending upon the nature of the obstruction, heat may be beneficial in actually melting or loosening the obstructing material, permitting the gland to begin production and excretion of lipids and other fluids more freely.
  • NIR near infrared
  • two hard eye patches were attached to an eye mask according to the pupillary distance of the subject.
  • the eye mask was held in place by an elastic headband.
  • Each patch employed 19 light emitting diodes, emitting near infrared radiation from 850 nm to 1050 nm, with a peak at 940 nm.
  • the device produced 10 mW/cra 2 of energy operating on electrical power. Goto, E., et al., Treatment of Non- Inflamed Obstructive Meibomian Gland dysfunction by an Infrared Warm Compression Device, British Journal of Ophthalmology, Vol. 86 (2002), pp. 1403-1407.
  • This device is designed as a non-contact infrared heating mask using IR light emitting diodes.
  • IR heating mechanism there are many potential problems with use of an IR heating mechanism.
  • the IR Heat can penetrate beyond the eyelid into the cornea which is undesirable, and could ultimately cause cataracts or other damage.
  • the IR mask heater places no pressure whatsoever on the eyelid (despite the description as a compression device) which we have determined is useful to expel the blockage.
  • tests conducted on a sample of this mask revealed that in spite of the potential dangers, the mask produced very little actual heat.
  • United States Patent Publication US2004/0237969 titled “Therapeutic Eye and Eye Lid Cover” comprises a pair of goggles that are adapted to deliver heated saturated air to the eyelids and particularly to the meibomian glands, again to heat the gland. Heat treatment of the eyes is also discussed in the article titled “Tear Film Lipid Layer Thickness and Ocular Comfort after Meibomian Therapy via Latent Heat with a Novel Device in Normal Subjects by Mitra et al, published in Eye, (2004) at pages 1 -4.
  • a method of treating mammalian meibomian glands involves clearing the glands by applying a regulated heat to an eyelid containing the meibomian glands to a temperature adequate to melt obstructions in the meibomian glands, thereby placing the obstruction in a fluid or suspension (melted) state, and maintaining the heat for a time period adequate to melt the obstructions and place the obstructions in the fluid or suspension (melted) state.
  • the glands can then be mechanically treated to express fluid from the glands, wherein the treating is carried out either during the time period or after the time period but while the obstruction remains in the fluid or suspension state. In most instances, this should be carried out within about 90 seconds of the end of the time period.
  • Subsequent pharmacological treatment of the glands by use a pharmacological agent topical or systemic
  • the time period can be approximately 10 to 60 minutes, and approximately 15 minutes is generally suitable for mild to moderate cases of MGD. In more severe cases, treatments of 30-45 minutes may be required, and for very severe cases, up to and beyond 60 minutes of heat treatment may be needed. These times assume a target temperature of 44-47 degrees with 45 degrees C being preferred, and may possibly be reduced somewhat for higher temperatures or extended somewhat for lower temperatures. Temperatures can range from 37 degrees Celsius and up.
  • the mechanical treatment is carried out by at least one of application of constant pressure, vibratory energy, mechanical energy, pulsating mechanical stimulation, squeezing, milkingly expressing the fluid from one or more of the glands while simultaneously applying heat, or applying vibratory stimulation to the eyelid while simultaneously applying heat.
  • a method of treating meibomian gland dysfunction in a mammal wherein an occlusion blocks at least a portion of the flow of naturally occurring secretions out of a gland channel orifice involves applying a regulated heat source proximate to the gland channel orifice for a selected time and at a selected temperature adequate to soften or liquefy at least a portion of the occlusion; mechanically treating the gland channel orifice while the at least a portion of the occlusion remains softened or liquefied such that at least a portion of the occlusion is removed; subsequently treating the mammal with a pharmacological agent which promotes the free flow of lipids from the meibomian gland or otherwise assist in the promoting lubrication of the eyes.
  • a method of treating meibomian gland dysfunction in a mammal wherein an occlusion blocks at least a portion of the flow of naturally occurring secretions out of a gland channel orifice involves applying a regulated heat source proximate to the gland channel orifice for a selected time and at a selected temperature adequate to loosen, breakup, fracture, soften or liquefy at least a portion of the occlusion; mechanically treating the gland channel orifice prior to reversal of the effects of the application of the regulated heat source such that at least a portion of the occlusion is removed; subsequently treating the mammal with a pharmacological agent which promotes the free flow of lipids from the meibomian gland or otherwise assist in the promoting lubrication of the eyes.
  • FIGURE 1 depicts upper and lower human eyelids showing the meibomian glands.
  • FIGURE 2 is a cutaway view of an illustrative meibomian gland 20.
  • FIGURE 3 is a cutaway view meibomian gland 20 illustrating several obstructed areas.
  • FIGURE 4 is a graph of inner and outer surface temperatures of a patient's eyelid while the outer surface of the eyelid is heated to about 45 degrees C.
  • FIGURE 5 is a flow chart depicting a treatment process consistent with certain embodiments of the present invention.
  • FIGURE 6 is a flow chart depicting another treatment process consistent with certain embodiments of the present invention.
  • the terms “a” or “an”, as used herein, are defined as one or more than one.
  • the term “plurality”, as used herein, is defined as two or more than two.
  • the term “another”, as used herein, is defined as at least a second or more.
  • the terms “including” and/or “having”, as used herein, are defined as comprising (i.e., open language).
  • the term “coupled”, as used herein, is defined as connected, although not necessarily directly, and not necessarily mechanically.
  • program or “computer program” or similar terms, as used herein, is defined as a sequence of instructions designed for execution on a computer system.
  • a "program”, or “computer program” may include a subroutine, a function, a procedure, an object method, an object implementation, in an executable application, an applet, a servlet, a source code, an object code, a shared library / dynamic load library and/or other sequence of instructions designed for execution on a computer system.
  • MMD meibomian gland dysfunction
  • Obstructions or occlusions of the meibomian glands may be present at the orifice of the gland, the main channel of the gland, or possibly in other locations including the main channel of the gland which may be narrowed or blocked. It has been theorized that the acini of the glands may have valves at their junction with the main channel of the gland, and that these valves may be obstructed in some instances leading to reduced or blocked flow from the acini. These obstructions or occlusions may have various compositions.
  • each gland includes a central duct or channel 18 into which the secretion flows from acini 19 and an orifice 20 which opens on to the eyelid margin and through which the secretion flows in order to be added to the tear film upon blinking. It will be seen that the glands are of different size, depending upon the location in the eyelid and that the orifice 20 is narrower than the central duct IS.
  • Obstruction composition will vary with the etiology which produced it.
  • the obstruction will, in most cases observed to the present, be a combination of, dead cells, bacteria, desquamated cells, and desquamated cells aggregating in keratotic clusters, milky fluid, inspissated or creamy secretions, or any combination of the foregoing in solid, semisolid and thickened forms.
  • FIGURE 3 a simplified view of exemplary obstructions to gland 10 are depicted. In this example, which is by no means necessarily representative of all meibomian gland obstructions, as explained above, a solid or semi-solid or thickened plug 24 is depicted which is fully occluding the orifice 20 of gland 10.
  • Another obstruction 26 is shown at a junction from one of the acini with the central duct. As previously noted, this may be the site of a valve in the gland structure, but embodiments consistent with the present invention should not be limited by theories of the actual meibomian gland structure. A number of treatment techniques have been proposed to restore these glands to normal functionality, but most doctors agree that heat is beneficial in treating MGD. Depending upon the nature of the obstruction, heat may be beneficial in actually melting or loosening the obstructing material or material binding solid particles to form the obstruction, permitting the gland to begin production and excretion of lipids and other fluids more freely.
  • the outside skin surface of the human eyelid has been observed to be approximately 1-2 degrees Celsius cooler than body temperature, with some variation. Increasing the temperature to at least 37 can begin to provide therapeutic effect for milder cases of MGD.
  • One preferred range for treatment is 44 to 47 degrees Celsius, with a target of 45 degrees Celsius has been found effective and comfortable to the patient.
  • the mechanical energy treating is carried out during or immediately after the end of the time period, and preferably with a heated instrument so as to maintain the more fluid state of the obstruction.
  • Mechanical energy treatment can be carried out by any mechanism that induces mechanical pressures, including but not limited to vibratory, milking, mechanical pulsing pressure, squeezing and other actions to express fluids from the glands and/or dilate the duct or orifice of the meibomian gland.
  • the mechanical energy can take any form that applies mechanical pressure on the meibomian glands to assist in pushing the blockage or obstruction out of the gland while the obstruction is softened by heat.
  • Even higher temperatures e.g., 50-55 degrees Celsius
  • higher temperatures can be used for shorter periods of time.
  • the temperature and time used should be individualized based on the severity of the condition and the tolerance of the patient. It has been found that lighter skinned patients can generally tolerate less heat than darker skinned patients, and darker skinned patients tend to exhibit less inflammation as a result of exposure to the heat. Treatment times and/or temperature can be adjusted to account for these differences. Each of the above temperatures refers to the temperature as measured at the outer surface of the eyelid.
  • the patient is more comfortable when the treatment begins at a lower temperature and the temperature is raised over time.
  • the temperature should be regulated, where regulation should be interpreted to mean that the actual temperature applied at the outer surface of the eyelid is controlled or regulated in a manner that is repeatable.
  • the temperature profile for heat application may be a constant temperature, or may have ramp-ups, ramp-downs, peaks, valleys, can be pulsed, or can be modulated with various characteristics, etc., but such profile should be regulated so as to be repeatable. It has also been found that modulating the temperature can result in a higher average temperature than a constant temperature, and may be useful in some applications.
  • This temperature can be maintained at a therapeutic temperature for a treatment period of approximately 10-60 minutes (or even beyond have been found safe and useful for some patients). Either during or after such treatment by controlled heat, mechanical expression of lipids and other fluids from the meibomian glands has been found to clear obstructions which have essentially melted or been placed in a suspension state (by virtue of melting materials binding solids together).
  • such devices that apply regulated heating of the eyelids are disclosed in U.S patent application number 11/434,054, filed May 15, 2006 and entitled Method and Apparatus for Treating Meibomian Gland Dysfunction to Korb, et al and U.S. patent application number 11/434,033, filed May 15, 2006 entitled “Melting Meibomian Gland Obstructions", to Steve Grenon, et at, which are hereby incorporated by reference.
  • that device utilizes a heater unit having a heating element that produces heat when an electrical signal is applied thereto.
  • a temperature regulator applies the electrical signal to the heating element in order to achieve heating of the heating element to a specified temperature range.
  • An eyelid interfacing mechanism couples the heater unit to the eyelid to achieve regulated heating of the eyelid within the specified temperature range.
  • Such a device provides regulated heating to a therapeutic temperature.
  • Conventional hot compresses and the IR heating mechanisms described above background do not provide regulated controlled heating at a therapeutic temperature and are less effective than the regulated heat applied using the devices described in the above-referenced patent applications that are incorporated herein.
  • an apparatus that provides controlled heat to at least one of a patient's eyelids has a heater unit, and the heater unit having: a heating element having first and second surfaces that produces heat when an electrical signal is applied thereto; a thermal heat sink, coupled to the first surface of the heating element in order to transfer heat from the heating element to the eyelid; an insulator coupled to the second surface of the heating element in order to reduce heat loss from the second surface; and a back plate that couples to the insulator.
  • a temperature regulator applies the electrical signal to the heating element in order to achieve heating of the heating elements to a specified temperature range.
  • Goggles suitable for attaching to the patient's head and covering the eyelid of the patient with a lenspiece are provided with the lenspiece having a threaded aperture therein.
  • a threaded shaft passes through the threaded lenspiece and coupled to the heater unit at the back plate so that the heater unit can be moved into contact with the eyelid by screwing the shaft into the aperture until contact with the eyelid is achieved.
  • the eyelid interfacing mechanism comprises goggles that are adjustably coupled to the heater unit in order to move the heater unit to achieve contact with the eyelid.
  • the goggles may be adjustably coupled to the heater unit by a threaded connection so that a position of the heater unit can be adjusted by a threading action.
  • the heater unit has a thermal heat sink, coupled to a surface of the heating element in order to transfer heat from the heating element to the eyelid.
  • the thermal heat sink may be, for example, at least one of a thermally conductive rubber member, a thermally conductive silicon member, an encapsulated fluid containing member, and a solid conductive member.
  • a thermally conductive gel, cream or liquid can be placed between the heat sink and the eyelid to enhance thermal conduction from the thermal heat sink to the eyelid.
  • the heater unit may have an insulator coupled to a surface of the heating element in order to reduce heat loss from the heating unit in a direction other than a direction toward the eyelid.
  • the thermal insulator may be one of a non-thermally conductive foam element, a non-thermally conductive rubber element, and a non-thermally conductive solid element in certain embodiments.
  • the temperature regulator may apply a pulse width modulated electrical signal to the heating element in order to regulate the heat produced thereby, and the pulse width modulated electrical signal may be produced under control of the control processor.
  • the temperature regulator may incorporate a switch that selectively applies the electrical signal to the heating element in order to regulate the heat produced thereby.
  • the electrical signal may be at least one of a current and a voltage that is selectively applied to the heating element under control of a control processor.
  • the heater unit may have a flexible portion that contacts the eyelid in order to conform to the eyelid or may have a rigid portion that contacts the eyelid, and wherein the rigid portion is shaped to conform to the shape of the eyelid, or a combination thereof.
  • the heater unit may have an adhesive for attaching the heater unit directly to the eyelid or may be attached to the eyelid by use of adhesive tape.
  • a user interface permits a user to establish at least one of a time and a temperature for the treatment.
  • a vibration generator generates vibration of the eyelid to stimulate secretion from the meibomian glands, wherein the vibration generator may imparts mechanical energy to the eyelid having both an amplitude and frequency.
  • FIGURE 4 a graph depicts the inner surface of an eyelid and an outer surface of an eyelid when a source of constant heat at about 45 degrees C was applied to an example subject patient.
  • the circulatory system attempts to regulate the temperature of the eyelid, and blood flow increases with the application of heat.
  • a 45 degree constant heat source it may take at least about 4 minutes to stabilize eyelid temperature and reach a therapeutic temperature.
  • the heat source is removed from the eyelid, the temperature drops very quickly to body temperature.
  • this temperature will drop within 2-3 minutes, but more commonly, only about 30 seconds to 90 seconds are required for the patient's eyelid temperature to drop. In this example, the temperature dropped in temperature very quickly over the first thirty seconds after removal of the heat. During this short time period, some or all of the melted obstruction may re-solidify.
  • the manual expression should follow immediately, or within about 90 seconds — with shorter intervals being preferred, e.g., within 30 seconds, or in any event, prior to reversal of the effects of the application of the regulated heat source such that at least a portion of the occlusion is removed.
  • pharmacological agents may assist in promoting tear production or otherwise assisting in the lubricating function of the eye by promoting an improvement in the tear film. Used alone, such treatments may be ineffective or only partially effective, whereas, used after clearing of the meibomian glands may restore normal or near normal production of all components of the tear film. Hence, many pharmacological agents may be appropriate for further enhancement of the tear film and may be extremely beneficial once the meibomian glands are returned to more normal function.
  • treatment with various pharmacological agents can be beneficial to maintaining the flow of lipids from the glands.
  • a treatment regimen is described starting at 100, after which a controlled heat such as produced by the various apparatus described in the above-referenced and incorporated by reference patent applications is applied to the eyelids at 104.
  • the preferred heat is greater than 37 degrees Celsius, with a preferred range of heat between approximately 44-47 degrees Celsius, with a target of 45 degrees Celsius.
  • mechanical force can be applied at 108 in any of the above mechanical modalities discussed to express the fluids or suspensions from the meibomian glands while the obstructions are in the melted state.
  • any instrument used in the expression process be heated so as to simultaneously apply or assist in maintaining heat to the glands at the time of expression.
  • any instrument used in the expression process be heated so as to simultaneously apply heat or assist in maintaining heat to the glands at the time of expression.
  • the meibomian glands can be treated with any of a variety of pharmacological agents, either topical or systemic) in order to minimize inflammation of the glands, clear infections, prevent further blockages, thin the lipids, promote production of tears, enhance the composition of the tear film, or any other pharmacological modality that promotes the free flow of the lipids or enhanced lubrication of the eye at 112.
  • pharmacological agents either topical or systemic
  • Pharmacological treatment may be carried out either for a short duration (e.g., to clear an infection or inflammatory condition), or for ongoing therapy (e.g., as in pharmacological agents that thin the lipids, reduce inflammation or treat other modalities of dry eye syndrome). This process ends at 116.
  • pharmacological agents have been proposed for treatment of dry eye syndrome, any of which may be effective or more effective upon clearing of obstructions within the meibomian glands.
  • Some of the pharmacological agents that may be utilized include, but are not limited to: antibiotics such as topical or oral tetracycline and chemically modified tetracycline, testosterone, topical or oral corticosteroids, topical androgens or androgen analogues, omega 3 fatty acid compounds such as fish oils, laennec, enzymes that promote lipid production, agents that stimulate production of enzymes that promote lipid production, and any agent which acts as a secretagogue to enhance meibomian gland secretion or secretion of other tear components.
  • Androgen and androgen analogues and TGF- ⁇ have been reported to act as a secretagogue to enhance meibomian gland secretion, agents that replace or promote production of any tear component, and there are likely many others. These compounds are illustrative examples of appropriate pharmacological agents, but those skilled in the art will appreciate that other pharmacological compounds may be utilized upon consideration of the present teachings. It is further noted that multiple modalities may be involved in causing dry eye syndrome, but treatment of only one modality may not result in full resolution.
  • the restoration of normal or near normal lipid flow from the meibomian glands may be only a part of the solution — with pharmacological treatment of the other modality or modalities of the disease restoring a normal tear film.
  • treatment of the other modalities alone is likely to be less than satisfactory.
  • FIGURE 6 A variation of the above treatment is described in connection with FIGURE 6 starting at 130, after which a controlled heat such as produced by the various apparatus described in the above-referenced and incorporated by reference patent applications is applied to the eyelids at 104 as in the prior treatment method.
  • the preferred range of such heat is again between approximately 44-47 degrees Celsius, with a target of 45 degrees Celsius.
  • time ranges from about 10 to 60 minutes and beyond may be used, depending upon severity of the condition, the treatment temperature and patient tolerance.
  • mechanical force can be applied at 138 in any of the above mechanical modalities discussed, including those referenced and incorporated by reference, to express the fluids or suspensions from the meibomian glands while the obstructions are in a liquid or suspension state during application of the heat.
  • additional force can be applied immediately subsequent to removal of the heat at 142.
  • heat be maintained during the time of expression or force being applied as described. That is, it is preferred that any probe or other instrument used during the expression be heated to help maintain the obstruction in a liquid or suspension state.
  • Such force can be manually applied by squeezing the eyelids at appropriate locations where obstructions appear to remain, or automated mechanical means may be employed if available.
  • the meibomian glands can be treated with any of a variety of pharmacological agents, either topical or systemic) in order to minimize inflammation of the glands, clear infections, prevent further blockages, thin the lipids or any other pharmacological modality that promotes the free flow of the lipids or otherwise promote an improved tear film at 112 as before.
  • pharmacological treatment may be carried out either for a short duration (e.g., to clear an infection or inflammatory condition), or for ongoing therapy (e.g., as in pharmacological agents that thin the lipids, improve the tear composition, or reduce inflammation). This process ends at 150.
  • a method of treating mammalian meibomian glands involves clearing the glands by applying a regulated heat to an eyelid containing the meibomian glands to reach a temperature adequate to melt obstructions in the meibomian glands and maintaining the heat for a time period adequate to melt the obstructions and place the obstructions in a fluid or suspension (melted) state.
  • the glands can then be mechanically treated to express fluid or suspension from the glands, wherein the mechanical treatment is carried out either during the time period or after the time period but while the obstruction remains in the melted state.
  • the process may be enhanced by a heated treatment device for applying the force to maintain the temperature and the melted state of the obstructive material.
  • Subsequent pharmacological treatment of the glands by use a pharmacological agent (topical or systemic) can then be used to assist in maintaining proper flow of lipids from the glands.
  • the time period can be approximately 10 to 60 minutes, and approximately 15 minutes is 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 with a target of 45 degrees Celsius at the eyelid's outer surface has been found effective and comfortable to the patient.
  • the mechanical treating is carried out as soon as possible after the heating, and preferably within about 30-90 seconds, so that the obstruction will remain in a melted state during the expression process.
  • the mechanical treatment is carried out by at least one of application of constant pressure, squeezing, milkingly expressing the fluid or suspension from one or more of the glands while simultaneously applying heat, or applying vibratory stimulation to the eyelid while simultaneously applying heat.

Abstract

L'invention concerne un traitement de Meibomius. Dans un mode de réalisation selon la présente invention, un procédé de traitement des glandes de Meibomius de mammifère (10) met en jeu le dégagement des glandes par l'application d'une chaleur régulée (104) à une paupière contenant les glandes de Meibomius à une température suffisante pour faire fondre les obstructions dans les glandes de Meibomius pour mettre les obstructions dans un état de fluide ou de suspension (fondu), et le maintien de la chaleur pendant une période de temps suffisante pour faire fondre les obstructions. Les glandes peuvent alors être traitées mécaniquement pour exprimer un fluide à partir des glandes (108), le traitement étant réalisé soit pendant la période de temps, soit après la période de temps, mais pendant que l'obstruction reste dans un état fluide. Un traitement pharmacologique ultérieur des glandes par l'utilisation d'un agent pharmacologique (topique systémique) (112) peut alors être utilisé pour aider à conserver un écoulement correct de lipides à partir des glandes. Cet abrégé ne doit pas être considéré comme limitatif de la portée de l'invention, car d'autres modes de réalisation peuvent s'écarter des caractéristiques décrites dans cet abrégé.
EP07716448A 2007-01-09 2007-01-09 Traitement des glandes de meibomius Withdrawn EP2101697A4 (fr)

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CN101553195A (zh) 2009-10-07
WO2008085162A1 (fr) 2008-07-17

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