Patent Description:
Pain is a major limiting factor in many common procedures performed in the inpatient and ambulatory care settings. A very abbreviated list includes skin biopsy, fine needle aspiration biopsy, IV insertion, vaccination, injections (including injection of anesthetics), blood draws, central line placements, and finger and heal pricks for blood analysis (glucose measurement). Pharmacologic anesthesia is a primary method of pain reduction, but the delivery of local pharmacologic anesthesia usually requires a painful injection. Other methods of providing anesthesia include the application of cold temperatures through ice, liquid evaporation, or a low temperature substances. These methods of anesthesia are limited in part by the lack of temperature control and the inability to tightly focus the tissue area receiving anesthesia. The present device improves patient comfort by providing tightly controlled, focal cooling to the tissue needing anesthesia or analgesia. <CIT> uses a cooling applicator for cooling corneal tissue.

The ocular surface is a tissue surface to which the present device can be applied, but is not limited to. The ability to deliver medication directly into the eye via intravitreal injection therapy (IVT) has transformed the treatment landscape of a number of previously blinding diseases, including macular degeneration and diabetic retinopathy. The success of these therapies in preventing blindness has resulted in a dramatic increase in the number of intravitreal injections performed, with an estimated <NUM> million injections given in the United States alone in <NUM>. The number of indications for IVT continues to expand, increasing utilization of this therapy significantly every year. The primary limitations of IVT are patient discomfort, ocular surface bleeding, and the time constraints of treating the vast number of patients requiring this therapy. These drawbacks relate to the difficulty of delivering ocular anesthesia to the highly vascularized ocular surface.

To give an ocular injection, the physician first provides ocular surface anesthesia by one of a number of methods, including the following: topical application of anesthetic drops; a subconjunctival injection of lidocaine; placement of cotton tipped applicators soaked in lidocaine above the planned injection site, placement of topical anesthetic gel, or some combination of these. Following ocular anesthesia, the physician or an assistant sterilizes the periocular region by coating it in betadine or a similar antiseptic. An eyelid speculum is then placed, and the physician marks the location of the injection using calipers that guide placement of the needle. The ocular surface is again sterilized, and the physician gives the injection.

Current methods of local anesthesia have unique drawbacks and patients often experience discomfort during and after intraocular injections. The number of indications for IVT continues to expand, increasing utilization of this therapy significantly every year. In light of this need, we have designed a device to deliver rapid anesthesia and vasoconstriction through the cooling of the surface of the tissue at the injection site, which will be discussed in greater detail herein.

Most patients receiving IVT receive multiple injections per year. In <NUM>, Friedman and colleagues applied age, ethnicity, and gender specific rates of AMD to the <NUM> census and estimated that <NUM> million Americans had exudate macular degeneration. Population based estimates suggest that this number will increase to <NUM> million or more by the year <NUM>. Using these same principles, Western Europe was estimated to have over <NUM> million patients with exudative macular degeneration in <NUM>. These numbers are likely underestimates of the true prevalence of disease. The majority of these patients are receiving IVT multiple times per year in one or both eyes. Recent studies have demonstrated that IVT is at least as successful as laser therapy to treat vision threatening retinal disease in patients with diabetic retinopathy and retinal vein occlusions, and this has resulted in wider adoption of IVT in these patients. The number of patients with treatable retinal diseases has increased steadily and will continue to grow over the next several decades. This has led to severe strain on clinic work flow, as IVT is a time-consuming procedure. Vitreoretinal surgeons perform these injections in busy clinics, frequently treating <NUM> to <NUM> patients per day. These injections are painful, and ophthalmologists typically choose one of two anesthesia options for IVT. The most common is to provide maximal anesthesia by one of two methods, which increases the time for patient preparation by several fold. The second option is to provide minimal anesthesia via topical drops, which is more time efficient, but results in significant patient pain. Both methods require a technician to prepare each patient. Developing a device to provide rapid anesthesia of the ocular surface will improve patient comfort and physician efficiency.

A recent case report and our own clinical experience show that excellent anesthesia is possible with the application of ice to the ocular surface. This therapy has been used for patients with allergies to lidocaine, but has much broader implications for all patients receiving IVT. Additionally, histopathologic safety data from historic studies of cryotherapy for the treatment of retinal tumors have shown that the operable temperature of the present device will not result in ocular tissue damage. Thus, the present device can improve patient comfort while simultaneously increasing physician efficiency delivering IVT.

Thermoelectric cooling provides reliable refrigeration as well as precise temperature control by direct electric feedback, which is hard to achieve with other available cooling techniques such as liquid evaporation, Joule-Thomson cooling, a thermodynamic cycle (e.g., a Stirling cooler or vapor compression refrigeration cycle), an endothermic reaction, or a low-temperature substance (e.g., liquid nitrogen). However, current thermoelectric (Peltier) modules have a low coefficient of performance (COP) and do not provide sufficient cooling power flux to maintain tissue at a temperature relevant for anesthesia (e.g., -<NUM>) if a single unit is placed with its cooling surface in contact with tissue. As specified in the present teachings, the present device adopts a novel cooling power concentrator that collects the cooling power of multiple (or single) Peltier modules and concentrates this cooling over a small area, producing a sufficient cooling power flux required for rapid and sustainable low temperature cooling of tissue. In addition, the cooling power concentrator allows multiple Peltier modules to be distributed over a large area, minimizing the heat flux rejected from Peltier modules to the heat sink and hence relaxing the heat dissipation requirements of the heat sink.

According to the principles of the present teachings, a cryoanesthesia or analgesia device and method of use in ocular treatments is provided that allows for rapid administration of anesthesia to the eye, for example, for administration of intravitreal injections, for example. In some embodiments, by providing cooling of the conjunctiva and sclera at the injection site, patient discomfort is minimized.

In some embodiments, the cryoanesthesia device of the present teachings is designed to achieve a cold temperature quickly by means of a thermoelectric (Peltier) device, liquid evaporation, Joule-Thomson cooling, a thermodynamic cycle (e.g., a Stirling cooler or vapor compression refrigeration cycle), an endothermic reaction, and a low-temperature substance (e.g., liquid nitrogen). The cryoanesthesia device may be sufficiently sized to be handheld or be part of a larger unit, and may include safety mechanisms to limit cooling to a defined temperature, maximum heat flux, or time period in order to prevent damage to ocular or other biological tissue. In some embodiments, the cryoanesthesia device of the present teachings can comprise an applicator attached to a larger cooling unit. The cryoanesthesia device may be a stand-alone, hand-held unit. Use of the cryoanesthesia device of the present teachings improves anesthesia and reduces pre-injection prep time for patients and physicians.

It should be understood, however, that the cryoanesthesia device of the present teachings can be used to decrease pain in any part of the body, including, but not limited to, the cutaneous membranes, mucous membranes, and tissue of the mucocutaneous zone.

The present invention is disclosed in independent claim <NUM>.

Spatially relative terms may be intended to encompass different orientations of the cryoanesthesia device in use or operation in addition to the orientation depicted in the figures. For example, if the cryoanesthesia device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. The cryoanesthesia device may be otherwise oriented (rotated <NUM> degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

It should be understood that the present teachings will be described in connection with an eye. However, the principles of the present teachings are equally applicable for use with other biological tissue, including skin, organs, membranes, nasal mucosa, and the like. Accordingly, the disclosure should not be regarded as being limited to eyes, unless otherwise limited in the claims, but may include all biological tissue.

According to the principles of the present teachings a cryoanesthesia device is provided having advantageous construction and method of use. In some embodiments, the cryoanesthesia device is configured to provide rapid anesthesia to the ocular surface to aid in the administration of intravitreal injections or other medical procedures. Generally, the ocular surface is regarded as that portion of an eye that is exposed to the external environment. However, in some embodiments, the ocular surface can include the cornea and its major support tissue, the conjunctiva. In a wider anatomical, embryological, and also functional sense, the ocular mucosal adnexa (i.e. the lacrimal gland and the lacrimal drainage system) can be part of the ocular surface. The cryoanesthesia device of the present teachings rapidly achieves cold temperatures, such as through thermoelectric cooling, utilizing a thermodynamic cycle, utilizing an endothermic reaction, or the use of a cold substance such as liquid nitrogen to impart localized cooling to produce regional anesthesia. Such cryoanesthesia slows conduction of pain fibers in the conjunctiva (outermost layer of the eye) and the sclera (white of the eye).

The present teachings may have application in rapid, complete ocular anesthesia that can be given immediately prior to intravitreal injections, fine-needle aspiration biopsies, lacrimal and nasolacrimal system biopsies, and a wide variety of peri-ocular procedures including, but limited to, eyelid biopsies, peri-orbital injections of pharmacologic anesthetics, and eyelid lesion excisions. Accordingly, the present teachings provide numerous advantages, including but not limited to decreased time to achieve ocular anesthesia compared to current methods, more complete ocular anesthesia resulting in decreased pain from intravitreal injections, decreased ocular surface bleeding, and avoidance of the side effects of topical and injectable anesthetic medications.

The present teachings have application in rapid anesthesia of cutaneous membranes, mucous membranes, and tissue of the mucocutaneous zone. The cooling of nerve conduction can facilitate decreased pain prior to injections, IV placement, incisional and excisional biopsies, fine-needle aspiration biopsies, and a variety of other procedures including but not limited to finger sticks prior to glucose measurement.

With reference to the figures, a device <NUM> is provided having an advantageous construction and method of use for cryoanesthesia and/or analgesia (however, for brevity, device <NUM> will be referred to as cryoanesthesia device <NUM>, but will have utility in both cryoanesthesia and analgesia applications). Specifically, in some embodiments as illustrated in <FIG>, cryoanesthesia device <NUM> can comprise an elongated body <NUM> having a proximal end <NUM> and a distal end <NUM>. As will be appreciated from the foregoing description, cryoanesthesia device <NUM> can be sized and shaped to be a handheld portable device conducive to use in a wide variety of medical procedures in both in-patient and out-patient facilities. Elongated body <NUM> can be shaped to include a gripping portion <NUM> generally disposed at a balanced midpoint location and/or a location generally adjacent proximal end <NUM> or distal end <NUM>. In the illustrated embodiment, gripping portion <NUM> is disposed generally between a midpoint location and distal end <NUM>.

With continued reference to <FIG>, in some embodiments, elongated body <NUM> can comprise a neck portion <NUM> providing a transition between a proximal portion <NUM> and gripping portion <NUM>. In some embodiments, gripping portion <NUM> can define a different cross-sectional shape relative to proximal portion <NUM> (e.g. a narrower shape), thereby resulting in neck portion <NUM> providing a transitional profile there between. It should be understood, however, that in some embodiments gripping portion <NUM> and/or proximal portion <NUM> can serve as a gripping portion to facilitate manipulation by a user. Therefore, the chosen nomenclature for proximal portion <NUM> and gripping portion <NUM> should not be regarded as limiting the invention, unless otherwise claimed. In some embodiments, cryoanesthesia device <NUM> is a handheld instrument measuring approximately <NUM> to <NUM> inches (<NUM> - <NUM>) in length and <NUM> to <NUM> inches (<NUM> - <NUM>) in diameter. However, alternative sizes are envisioned.

Generally, in some embodiments, cryoanesthesia device <NUM> cools a target area on the ocular surface to a predetermined temperature (e.g. in the range of about <NUM> to about -<NUM>) within a predetermined amount of time (e.g. in the range of about <NUM> second to about <NUM> seconds, in the range of about <NUM> second to about <NUM> seconds, or longer), thereby inducing cryoanesthesia required for ocular procedures, such as intravitreal drug injection. It should be understood that other temperatures ranges are included in the present teachings, including predetermined temperatures in the range of about <NUM> to about -<NUM> and in the range of about <NUM> to about -<NUM>. In some embodiments, cryoanesthesia device <NUM> comprises a thermoelectric (Peltier) cooling system <NUM> disposed within at least a portion of elongated body <NUM> for providing low temperature cooling of a cooling tip <NUM> disposed on distal end <NUM> of elongated body <NUM> to induce cryoanesthesia in the ocular surface. It should be understood that in some embodiments, a cooling system can comprise one or a combination of thermoelectric (Peltier) devices, liquid evaporation, Joule-Thomson cooling, a thermodynamic cycle (e.g., a Stirling cooler or vapor compression refrigeration cycle), an endothermic reaction, or a low-temperature substance (e.g., liquid nitrogen), which may or may not undergo a phase change.

In some embodiments, thermoelectric cooling system <NUM> comprises a cold tip <NUM>, a power source <NUM>, a controller <NUM>, a cooling power concentrator <NUM>, one or more Peltier unit modules <NUM>, and a heat sink <NUM>. It should be understood that, in some embodiments, thermoelectric cooling system <NUM> may include a heating element (not shown) that operates in conjunction with the cooling elements to precisely maintain a desired temperature and/or heat flux.

With particular reference to <FIG>, in some embodiments, cold tip <NUM> can be made of a thermally conductive material, such as a metal, and can be sized to be generally equal to or smaller than the target area of the ocular or other biologic surface. In some embodiments, the target area on the eye is a region that begins at the corneal limbus and extends anywhere from <NUM> to over <NUM> posterior to the limbus. In some embodiments, the end of the cold tip <NUM> is circular, approximately <NUM> in diameter including thermally insulating outer ring member <NUM>, which would correspond to the target area to be cooled. The thermally insulating outer ring member <NUM> restricts the area being cooled within the target area, which is touched by the thermally conductive cold tip <NUM>, preventing damage to adjacent cells outside the target area. In some embodiments, the thermally insulating outer ring member <NUM> visually guides the target area but does not touch the ocular or other biologic surface to prevent heat exchange with the thermally insulating outer ring member <NUM>. In some embodiments, a larger (or smaller) size of the cold tip can be used to provide anesthesia to cutaneous membranes, mucous membranes, or tissue of the mucocutaneous zone. In the illustrated embodiment, cold tip <NUM> is cylindrical in shape; however, it should be understood that alternative shapes are envisioned, including polygonal, oval, crescent, or any other conducive shape.

In some embodiments, power source <NUM> comprises a portable power source, such as a battery, capacitor, or similar device. In some embodiments, power source <NUM> can comprise a rechargeable lithium ion battery pack (<NUM> Wh), which provides sufficient energy on a single charge to operate cryoanesthesia device <NUM> at -<NUM> for approximately one hour. However, in some embodiments, power source <NUM> can comprise a non-portable power source.

Controller <NUM> can comprise a temperature regulating feedback loop to maintain highly accurate temperature control and/or a timed lockout mechanism to prevent excessive cooling. More particularly, in some embodiments, controller <NUM> can comprise a temperature sensor <NUM> operably coupled with at least one member of a thermal circuit comprising cold tip <NUM>, cooling power concentrator <NUM>, Peltier unit modules <NUM>, heat sink <NUM>, surrounding environment, and the ocular surface of the patient to output a temperature signal in response to a detected temperature. In this way, controller <NUM> receives the temperature signal and is operable to control an operating temperature of Peltier unit modules <NUM> via controlled current flow, controlled voltage, and/or pulse width modulation (PWM) of the DC battery source, thereby precisely regulating an operating temperature of cryoanesthesia device <NUM>. In some embodiments, temperature sensor <NUM> is arranged to directly measure the temperature of the ocular surface of the eye or any portion of the thermal circuit using any one or a number of thermal sensors, such as but not limited to thermistors, thermocouples, and resistance or optical thermometers. Controller <NUM> can then compute temperature and/or heat flux. Controller <NUM> can maintain a predetermined temperature or temperature range using a constant value, a pulse of certain magnitude and duration, or a more complex prescribed pattern. In some embodiments, cryoanesthesia device <NUM> can automatically power off if the tip temperature falls below a certain temperature (e.g., -<NUM>) to ensure a safe operating temperature range, and/or if a battery temperature exceeds <NUM> or the heat sink temperature exceeds <NUM>. In some embodiments, controller <NUM> can operate on the basis of applied, measured, or desired heat fluxes rather than applied, measured, or desired temperatures.

As described, controller <NUM> may further comprise a timed lockout mechanism that monitors and controls, via an integrated timer, the duration of cooling. In this way, controller <NUM> is capable of monitoring and achieving sufficient cooling of the target area on the ocular surface and prohibit excessive cooling thereof. In some embodiments, this timed cooling lockout is set to a predetermined time of approximately <NUM> seconds to approximately <NUM> seconds; however, additional durations are anticipated by the present teachings. It should be understood that the timed lockout mechanism may be used in combination with the temperature regulating feedback loop to both actively monitor and control both a measured temperature and a measured time.

In some embodiments, cooling power concentrator <NUM> is a generally, but not limited to, elongated concentrator made of a thermally-conductive material, such as but not limited to metal. Cooling power concentrator <NUM> can be disposed along a central longitudinal axis of elongated body <NUM>, and collects cooling powers of multiple Peltier units or that of a single Peltier unit. In some embodiments, cooling power concentrator <NUM> can be polyhedron in shape, and the cooling power collected from the surface(s) in contact with Peltier unit(s) is concentrated to one or more surfaces whose aggregate area is less than that of the Peltier unit cooling surface(s) at which collection occurs. However, it should be understood that cooling power concentrator <NUM> can have other shapes, including cylinder, cone, conical cylinder, sphere, hemisphere, or any other shapes that provide collecting and concentrating of cooling power. In such embodiments, Peltier unit modules <NUM> can be shaped to define a complementary surface to enhance surface area contact between Peltier unit modules <NUM> and cooling power concentrator <NUM> to facilitate thermoelectric cooling.

In some embodiments, cooling power concentrator <NUM> can be shaped to terminate at a compressible tip <NUM> that can be used to replace cold tip <NUM> prior to use and maintain its sterility. Compressible tip <NUM> can comprise a plurality of tapered flange members <NUM> extending radially from a main body portion <NUM> of cooling power concentrator <NUM>. The plurality of tapered flange members <NUM> collectively form a central bore sized to receive cold tip <NUM> therein to provide a mechanical and thermal coupling there between. The plurality of tapered flange members <NUM> are sized and shaped to provide independent flexibility to provide the mechanical coupling of cold tip <NUM> in response to compression exerted via a compression ring <NUM> threadedly engaging corresponding threads disposed on an exterior surface of the plurality of tapered flange members <NUM>. In this way, threaded engagement of compression ring <NUM> about the plurality of tapered flange members <NUM> results in the plurality of tapered flange members <NUM> being urged into a tighter, narrower nested relationship thereby exerting a compressive, retaining force upon cold tip <NUM>. Accordingly, threaded manipulation of compression ring <NUM> about the plurality of tapered flange members <NUM> can provide selective coupling and decoupling of cold tip <NUM> with cooling power concentrator <NUM>. It should be understood, however, that other fixture mechanisms such as a mechanical latch, magnetic coupling, bolt, or adhesive can be used to fix the cold tip. This is conductive to permitting cold tip <NUM> to be selectively replaced due to sterility and/or operational concerns. It should be understood that cold tip <NUM> is thus a replaceable tip that defines the contact cooling region of cryoanesthesia device <NUM> and provides a sterile surface for tissue contact. A replaceable or sterilizable tip coating <NUM> may also be integrated with cold tip <NUM> to provide a sterile surface for tissue contact.

In some embodiments, one or more Peltier unit modules <NUM> are disposed along, such as in an array, at least a portion of cooling power concentrator <NUM> to provide thermoelectric cooling of cooling power concentrator <NUM> and, thus, cold tip <NUM>. It should be understood that Peltier unit module <NUM> can be configured as a single cooling element or a plurality of cooling elements. However, it should be understood that there are particular benefits to employing a plurality of Peltier unit modules <NUM>, such as but not limited to redundancy of operation and the potential to source readily-available units from established industry. In some embodiments, the hot surface of Peltier unit module <NUM> is configured to be vertical with respect to central cooling portion <NUM> of cold tip <NUM>. However, it should be understood that the hot surface of Peltier unit module <NUM> can be parallel or in any angle with respect to central cooling portion <NUM> of cold tip <NUM> depending on the desired direction of heat rejection from Peltier unit modules <NUM>. In some embodiments, the plurality of Peltier unit modules <NUM> are operably coupled to power source <NUM> and controller <NUM> in such a way as to permit electrically parallel operation, thereby permitting cryoanesthesia device <NUM> to continue operation despite failure of one or more Peltier unit modules <NUM>. In such a case, controller <NUM>, and its associated feedback loop control system, can increase cooling output of the operable Peltier unit modules <NUM> to achieve desired cooling and/or duration performance.

While thermoelectric cooling has the advantages of being lightweight, small, solid-state (thus no fluids or moving parts), and electrically driven (thus allowing straightforward control of temperature), it rejects a large amount of heat that must be carefully managed. Cryoanesthesia device <NUM> provides a unique design for efficient heat spreading and dissipation. As described herein, cooling power concentrator <NUM> is thermally conductive and is cooled by one or more Peltier unit modules <NUM> to quickly and reliably maintain a predetermined temperature of cold tip <NUM>. The Peltier unit modules <NUM> are distributed to efficiently spread the heat rejected from Peltier unit modules <NUM> to heat sink <NUM> and therefore promote efficient cooling, which reduces the size of heat sink <NUM> and may enhance visual clearance between cold tip <NUM> and a user's eye. Heat sink <NUM> is made of a thermally conductive material to efficiently spread the heat rejected from Peltier unit modules <NUM>. In some embodiments, heat sink <NUM> is radially disposed about cooling power concentrator <NUM> and Peltier unit modules <NUM>. In other words, heat sink <NUM> radiates outwardly from a central longitudinal axis of cryoanesthesia device <NUM>. However, it should be understood that heat sink <NUM> can radiate heat in other directions depending on the relative angle of the hot surface of Peltier unit module <NUM> with respect to central cooling portion <NUM> of cold tip <NUM>. In some embodiments, heat sink <NUM> is disposed generally within gripping portion <NUM> and/or neck portion <NUM> of elongated body <NUM>, thereby providing localized heat sinking directly near Peltier unit modules <NUM> and cold tip <NUM>, while maintaining a narrow shape of gripping portion <NUM> for improved visual clearance during use and handheld capability.

To facilitate heat dissipation from heat sink <NUM>, an air circulation system <NUM> is provided for circulating air across fins or other features of heat sink <NUM>. In some embodiments, a fan <NUM> (see <FIG>) powered by power source <NUM> is actuated to draw air in from one or more inlet openings <NUM>. In some embodiments, inlet openings <NUM> comprise a plurality of fin channels <NUM> formed in heat sink <NUM> that are used to increase the surface area of heat sink <NUM> to facilitate heat transfer. In some embodiments, the surface roughness of heat sink <NUM> can be large to further increase the surface area of heat sink <NUM> in contact with air. Air passes along the plurality of fin channels <NUM> formed in heat sink <NUM> and generally surrounded by gripping portion <NUM> of elongated body <NUM>, along a direction generally, but not limited to, parallel to the central longitudinal axis of cryoanesthesia device <NUM>, and exits from one or more outlet openings <NUM> at a location far from cold tip <NUM>. It should be understood that the direction of air circulation can be perpendicular or in another angle to the central longitudinal axis of cryoanesthesia device <NUM> depending on the relative angle of the hot surface of Peltier unit modules <NUM> with respect to the surface of cold tip <NUM>. Locating outlet openings <NUM> far from cold tip <NUM> not only reduces convection loss at the tip surface of cold tip <NUM>, but also minimizes dryness of the patient's tissues due to airflow. Alternatively, air may be forced in the opposite direction and exit near the cold tip.

In some embodiments, cold tip <NUM> comprises a central cooling portion <NUM> being thermally coupled to cooling power concentrator <NUM>, and a thermally-insulating ring member <NUM> surrounding a peripheral side of central cooling portion <NUM>. Thermally-insulating ring member <NUM> is disposed to permit central cooling portion <NUM> to maintain an exposed contact tip configured to physically contact and thermally couple to a target area of the ocular surface, while simultaneously providing visual guidance regarding the position of the area to be cooled that is touched by the central cooling portion <NUM> with respect to the positions of nearby objects such as corneal stem cells and thereby prevent excessive cooling of these objects. In some embodiments, thermally-insulating ring member <NUM> includes an active heating element that controls the temperature adjacent to the cooled region in order to limit damage to surrounding tissue caused by cooling spread. In some embodiments, central cooling portion <NUM> of cold tip <NUM> defines an area of approximately <NUM><NUM> to approximately <NUM><NUM> (e.g. <NUM> × <NUM> to <NUM> × <NUM><NUM>).

With continued reference to <FIG>, in some embodiments, central cooling portion <NUM> of cold tip <NUM> can comprise targeting indicia <NUM> formed thereon configured to contact the target area of the ocular surface and provide a temporary marking for locating an anesthetized region. For example, in some embodiments, targeting indicia <NUM> can comprise a pair of protruding or indented features formed on cold tip <NUM> that temporarily results in markings on the ocular surface following removal of cryoanesthesia device <NUM>. These markings can be then used to properly locate an anesthetized region for placement of the IVT needle (e.g., placement of the intravitreal injection needle <NUM> or <NUM> from the corneal limbus). It should be understood that different targeting indicia <NUM> are envisioned, including but not limited to a circular or ring-shaped protrusion, multiple protrusions, or any other shapes that provide temporary markings.

In some embodiments, cryoanesthesia device <NUM> can comprise a replaceable/disposable tip coating <NUM> to provide a sterile surface for ocular contact and to mitigate formation of an ice adhesion between cryoanesthesia device <NUM> and the patient's eye. In some embodiments, tip coating <NUM> can comprise a hydrophobic polymer layer to mitigate ice adhesion between the cryoanesthesia device and tissue.

In some embodiments, a first switch member <NUM> is provided for actuation of cryoanesthesia device <NUM>. In some embodiments, switch member <NUM> can be used to set the cold tip temperature and timer duration, as well as power the Peltier modules. In some embodiments, operation of first switch member <NUM> comprises: <NUM>) clockwise rotation to increase the cold tip set temperature, <NUM>) counter-clockwise rotation to decrease the cold tip set temperature, <NUM>) clockwise rotation while the first switch member <NUM> is pushed, to increase the timer duration, <NUM>) counter-clockwise rotation while the first switch member <NUM> is pushed, to decrease the timer duration, and <NUM>) double-pressing to activate the Peltier modules.

A second switch member <NUM> located near gripping portion <NUM> can be used to activate (or deactivate) the timer. When the timer is activated, cryoanesthesia device <NUM> can produce audible indicia, such as two consecutive beeping sounds at low and high frequencies followed by beeping sounds every <NUM> seconds during the timer duration, and finally two long consecutive beeping sounds at high and low frequencies when the timer duration has expired. In some embodiments, first switch member <NUM> can be pushed before the set time is reached to terminate the timer function. It should be understood that cryoanesthesia device <NUM> can comprise any one of a number of control inputs, indicia, and techniques; accordingly, the presently described inputs, indicia, and techniques should not be regarded as limiting the invention.

During use, in some embodiments, cryoanesthesia device <NUM> is positioned in contact with the patient's eye such that cold tip <NUM> (or tip coating) is in physical direct contact with the target area of the ocular surface. Cryoanesthesia device <NUM> can be actuated "ON" via switch <NUM> either before or after being placed in contact with the patient's eye. Actuation of cryoanesthesia device <NUM> thereby initiates rapid cooling of cold tip <NUM> by controller <NUM>, cooling power concentrator <NUM>, Peltier unit modules <NUM>, heat sink <NUM>, and air circulation system <NUM>, while simultaneously marking the eye and anesthetizing the target area of the ocular surface. Following anesthetizing of the target area, a physician or care provider can then perform additional procedures, such as administering IVT. In some embodiments, a user may set a desired cold tip temperature and timer duration and then double-press first switch member <NUM> to activate Peltier modules <NUM> to bring cold tip <NUM> to a set temperature point (e.g. - <NUM>). Cold tip <NUM> can then be brought into contact with the patient's eye and the timer actuated. Cryoanesthesia device <NUM> then maintains the set temperature point for a set predetermined duration (e.g. <NUM> seconds) and then produces indicia such as, but not limited to, beep sounds or vibration. After the timer duration, cryoanesthesia device <NUM> can automatically adjust the tip temperature to a higher temperature (e.g., -<NUM>) to minimize ice adhesion between tissues and cold tip <NUM>, and then return to ambient temperature. As illustrated in <FIG>, tip temperature, along with power and voltage data, are illustrated along a time axis during operation.

In some embodiments, as illustrated in <FIG>, the cryoanesthesia device performs both anesthesia and injection (e.g., intravitreal injection). In some embodiments, a cooling power concentrator <NUM> is sterilized and replaceable. In some embodiments, cooling power concentrator <NUM> first induces cryoanesthesia at a tip <NUM>, after which the cryoanesthesia device performs injection (e.g., intravitreal injection). In some embodiments, a drug container <NUM> is placed inside the cooling power concentrator <NUM>, as illustrated in <FIG>. In some embodiments, a solenoid <NUM> or similar feature pushes the drug container <NUM>, compresses a spring <NUM> or similar feature, and inserts needle <NUM> within tissue (e.g., eye tissue). In some embodiments, solenoid <NUM> or similar feature controls the depth of needle insertion within tissue. In some embodiments, solenoid <NUM> or similar feature squeezes drug container <NUM>, causing drug to be injected, as illustrated in <FIG>. In some embodiments, needle <NUM> is placed outside of cooling power concentrator <NUM>, as illustrated in <FIG>. It should be understood, however, that the description above is provided for the purposes of illustration and does not limit the present teachings.

Claim 1:
A device (<NUM>) for cooling a target area of ocular tissue, the device (<NUM>) comprising:
an elongated body (<NUM>) having a gripping portion (<NUM>) to facilitate handheld manipulation by a user, the elongated body (<NUM>) having a proximal end (<NUM>) and a distal end (<NUM>):
a thermoelectric cooling system (<NUM>) disposed within at least a portion of the elongated body (<NUM>), the thermoelectric cooling system (<NUM>) configured to physically contact and thermally couple the target area to induce cryoanesthesia or analgesia, the thermoelectric cooling system (<NUM>) having:
a thermally-conductive cold tip (<NUM>) adapted to thermally contact the target area, the cold tip (<NUM>) being disposed on the distal end (<NUM>) of the elongated body (<NUM>);
a thermally-conductive cooling power concentrator (<NUM>) thermally coupled to the cold tip;
a plurality of Peltier unit modules (<NUM>) thermally coupled to the cooling power concentrator (<NUM>), the Peltier unit modules (<NUM>) operable to induce cooling of the cooling power concentrator (<NUM>);
a power source (<NUM>);
a thermal sensor detecting a temperature or heat flux of at least one of the cold tip (<NUM>), the cooling power concentrator (<NUM>), the Peltier unit modules (<NUM>), a surrounding environment, and the target area, the thermal sensor outputting a temperature or heat flux signal;
a controller (<NUM>) operably outputting a control signal to the Peltier unit modules (<NUM>) in response to the temperature or heat flux signal and a predetermined temperature or heat flux; and
a heat sink (<NUM>) thermally coupled to the Peltier unit modules (<NUM>).