Ocular cooling devices and associated methods

Abstract

The present technology comprises ocular cooling devices for reducing and / or controlling an eye temperature level. The ocular cooling devices may be useful in methods including, but not limited to, treating or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control. In some embodiments, the ocular cooling devices are portable.

Description

OCULAR COOLING DEVICES AND ASSOCIATED METHODSCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 602,298 filed November 22, 2023, the entire contents of which are incorporated herein by reference in their entireties.BACKGROUND

[0002] Retinal ischemia, characterized by insufficient blood perfusion of retinal tissue leading to progressive cell death, is a common cause of visual impairment and blindness. Current approaches for treating retinal ischemia through cooling methods have notable limitations. Such approaches typically involve applying ice packs to the face or performing corneal irrigation using cold saline, which present several drawbacks including challenges with proper storage, temperature regulation difficulties, limited cooling duration, and highly invasive procedures.

[0003] Various medical devices have been developed to address temperature control in ophthalmic applications, ranging from fluid circulation cooling devices to sophisticated systems incorporating temperature measurement and thermoelectric cooling components. However, existing technologies have not fully addressed the challenges of providing precise, controlled cooling specifically for treating retinal ischemia, indicating a need for improved solutions that offer more effective temperature regulation and targeted therapeutic delivery.SUMMARY

[0004] The present technology comprises ocular cooling devices and uses thereof for reducing and / or controlling an eye temperature level.

[0005] In some embodiments, the present technology comprises ocular cooling devices having: (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one ormore power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0006] In some embodiments, the present technology comprises ocular cooling devices having: (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: (a) a first side that contacts the subject’s eye; and (b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m*K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye; and(ii) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

[0007] In some embodiments, the present technology comprises ocular cooling devices having (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: (a) a first side that contacts the subject’s eye; and (b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m*K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube; and (iv) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

[0008] In some embodiments, the present technology comprises methods of reducing an eye temperature level in a subject in need thereof relative to a control, the method comprising positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce the eye temperature level in the subject.

[0009] In some embodiments, the present technology comprises methods of reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject.

[0010] In some embodiments, the methods reduce or prevent the ocular pain, the ocular inflammation, or the intraocular pressure during or after an ocular procedure.

[0011] In some embodiments, the ocular procedure comprises an intraocular injection.

[0012] In some embodiments, the control comprises the subject at baseline.

[0013] In some embodiments, the present technology comprises methods of treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject.

[0014] In some embodiments, the optic nerve injury comprises a traumatic optic nerve injury.

[0015] In some embodiments, the retinal ischemia is a retinal ischemia from central retinal artery occlusion (CRAO), non-arteritic ischemic optic neuropathy (NAION), retinal detachment, or ocular trauma.

[0016] In some embodiments, the method is performed in vivo.

[0017] In some embodiments, the ocular cooling device is a portable ocular cooling device.

[0018] In some embodiments, the contact ring is coupled by p-type and n-type semiconductor pillars to the thermoelectric cooler.

[0019] In some embodiments, the thermoelectric cooler is coupled to the chamber.

[0020] In some embodiments, the thermoelectric cooler is coupled to the contact ring or to the chamber with a thermally conductive adhesive, a locking mechanism, or a magnetic force.

[0021] In some embodiments, the magneticforce comprises a ferrous material.

[0022] In some embodiments, the ferrous material comprises a magnet.

[0023] In some embodiments, the cold side and the hot side of the thermoelectric cooler are coupled by p-type and n-type semiconductor pillars.

[0024] In some embodiments, the chamber is a heat exchanger.

[0025] In some embodiments, the chamber further comprises a fluid or a gas.

[0026] In some embodiments, the inlet tube allows for inlet of a cold fluid or a cold gas into the chamber.

[0027] In some embodiments, the outlet tube allows for outlet fluid or a gas from the chamber that is warmer than a fluid or a gas entering the chamber.

[0028] In some embodiments, the one or more power supply lines supply power to the thermoelectric cooler.

[0029] In some embodiments, at least a portion of an extraocular tissue of the subject’s eye positions over a flange of the contact ring.

[0030] In some embodiments, the extraocular tissue is an eyelid.

[0031] In some embodiments, at least a portion of the eyelid closes over the second side of the contact ring.

[0032] In some embodiments, the contact ring comprises a radius of curvature of at least about 2.0 mm to at least about 15.0 mm.

[0033] In some embodiments, one or more of the contact ring, the thermoelectric cooler, or the chamber comprises a central void.

[0034] In some embodiments, the central void comprises a diameter of at least about 5 mm to at least about 12 mm.

[0035] In some embodiments, the central void comprises a light penetrable window.

[0036] In some embodiments, the light penetrable window is a transparent window or a translucent window.

[0037] In some embodiments, the light penetrable window comprises a glass, an acrylic, a polycarbonate, or a transparent ceramic.

[0038] In some embodiments, the second side of the contact ring comprises a material having a thermal conductivity level that is less than 0.5W / (m»K).

[0039] In some embodiments, at least a portion of an anterior sclera, a cornea, a pupil, or a retina of the subject’s eye is visible through the central void.

[0040] In some embodiments, the contact ring comprises a non-transparent or an opaque material.

[0041] In some embodiments, the contact ring comprises a metal.

[0042] In some embodiments, the contact ring is comprised of a solid or homogeneous material.

[0043] In some embodiments, a contact area between the contact ring and the subject’s eye is anterior to a bulbus oculi equator of the subject’s eye.

[0044] In some embodiments, the material having a thermal conductivity level that is less than 0.5W / (m»K) is a silicone.

[0045] In some embodiments, the first side of the contact ring comprises a material having a thermal conductivity level that is at least 0.5W / (m»K).

[0046] In some embodiments, the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a material selected from the group consisting of glass, ceramic, metal, acrylic, and glass-ceramic.

[0047] In some embodiments, the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a thermally conductive additive.

[0048] In some embodiments, the thermally conductive additive is selected from the group consisting of carbon nanotubes, graphite, and aluminum powder.

[0049] In some embodiments, the first side of the contact ring decreases a heat level drawn from the portion of the extraocular tissue positioned over the flange of the contact ring, relative to a control.

[0050] In some embodiments, the contact ring is an eye cooling ring. In some embodiments, the contact ring further comprises one or more sensors or one or more electrodes.

[0051] In some embodiments, the one or more sensors comprise a pressure sensor, a temperature sensor, or an optical sensor.

[0052] In some embodiments, the temperature sensor comprises a thermistor.

[0053] In some embodiments, the one or more electrodes sense one or more biopotentials from a surface of the subject’s eye.

[0054] In some embodiments, the one or more sensors or the one or more electrodes contact at least a portion of the subject’s eye.

[0055] In some embodiments, the one or more sensors or the one or more electrodes are used as an input to a control circuit or a computational model.

[0056] In some embodiments, the ocular cooling devices further comprise a heat sink.

[0057] In some embodiments, the chamber comprises the heat sink.

[0058] In some embodiments, the heat sink is thermally coupled to the contact ring or to the hot side of the thermoelectric cooler.

[0059] In some embodiments, the heat sink is a finned heat sink.

[0060] In some embodiments, the inlet tube, the outlet tube, or the one or more power supply lines connect the ocular cooling device to a housing.

[0061] In some embodiments, the housing comprises one or more of a pump, a power supply, a heat dissipating component, or a rectifier.

[0062] In some embodiments, the housing is distally located to a limbus of the subject’s eye.

[0063] In some embodiments, the rectifier converts an alternating current (AC) to a direct current (DC).

[0064] In some embodiments, the rectifier powers the pump or the thermoelectric cooler.

[0065] In some embodiments, the heat dissipating component comprises a chemical cold pack, an ice bath, or a heat pump.

[0066] In some embodiments, the heat pump is a second thermoelectric cooler.

[0067] In some embodiments, the pump comprises a fluid or a gas.

[0068] In some embodiments, the fluid or the gas is transported by the inlet tube or the outlet tube of the ocular cooling device.

[0069] In some embodiments, the housing is a chest pack.

[0070] In some embodiments, the methods of the present technology or the ocular cooling devices or uses thereof reduce a temperature level in one or more of a retina, a vitreous, a posterior pole, or a proximal optic nerve of the subject’s eye.

[0071] In some embodiments, the methods of the present technology or the ocular cooling devices or uses thereof cool at least a portion of the subject’s eye to greater than about 5°C to less than 32°C.

[0072] In some embodiments, the subject is a human subject.BRIEF DESCRIPTION OF THE DRAWINGS

[0073] FIGS 1 A-11 illustrate planar views of an ocular cooling device configured in accordance with the embodiments of the present technology.

[0074] FIGS. 2A-2F illustrate features of a thermoelectric cooler of the ocular cooling device of FIGS. 1 A-11.

[0075] FIG. 3 illustrates features of a chamber of the ocular cooling device of FIGS. 1A-1 I.

[0076] FIGS. 4A-4D illustrate a heat sink configured with the ocular cooling device of FIGS. 1A-1 I.

[0077] FIGS. 5A and 5B illustrate certain features of a contact ring of the ocular cooling device of FIGS. 1 A-11.

[0078] FIGS. 6A-6C illustrate certain features of magnets for coupling the thermoelectric cooler and the contact ring of the ocular cooling device of FIGS. 1 A-11.

[0079] FIGS. 7A and 7B illustrate a locking mechanism of the contact ring of the ocular cooling device of FIGS. 1 A-11.

[0080] FIG. 8 illustrates certain features of an electrode of the ocular cooling device of FIGS. 1 A-11.

[0081] FIGS. 9A-9D illustrate certain features of sensors in the contact ring of the ocular cooling device of FIGS. 1 A-11.

[0082] FIG. 10 illustrates certain features of an insulating layer of the ocular cooling device of FIGS. 1 A-11.

[0083] FIGS. 11A and 11 B illustrate planar views of a wearable housing connected to the ocular cooling device of FIGS. 1A-1 I, configured in accordance with the embodiments of the present technology.

[0084] FIGS. 12A and 12B illustrate planar views of a housing comprising a pump connected to the ocular cooling device of FIGS. 1A-1 I, configured in accordance with the embodiments of the present technology.

[0085] FIG. 13 illustrates a computational model for controlling an eye temperature level using the ocular cooling device of FIGS. 1A-1 I.

[0086] FIGS. 14A and 14B illustrates temperature readings observed at three thermistor positions on a porcine eye using an ocular cooling device of the present technology (n=5).

[0087] FIG. 15 illustrates temperature readings observed at five thermistor positions on a porcine eye and one thermistor in an eye cooling ring using an ocular cooling device of the present technology.

[0088] FIG. 16A illustrates temperature readings from thermistors placed in contact rings. FIGS. 16B-16F illustrate temperature readings at different thermistor positions in porcine eye replicates (n=5).

[0089] FIG. 17 illustrates the average temperature observed at each of the six thermistor positions of FIG. 15.

[0090] FIGS. 18A-18D illustrate an ocular finite element thermal model. FIG. 1A illustrates a magnetic resonance imaging (MRI) image of an excised pig eye mounted in acrylic support ring, surrounded by canola oil. FIG. 18B illustrates a preliminary porcine eye model comprising manual segmentation of the image of FIG. 18A. FIG. 18C illustrates preliminary micro-computed tomography (CT) scan of a porcine eye with two implanted thermistors (arrows). FIG. 18D illustrates a preliminary human eye finite element model comprising a cross section of three-dimension model with mesh.

[0091] FIG. 19 illustrates the thermistor positions of FIGS 15-17.

[0092] FIGS. 20A and 20B illustrate imaging of a porcine eye. FIG. 20A illustrates an MRI slice through the porcine eye and thermistor positions ((1) anterior sclera; (2) equatorial sclera; (3) posterior sclera; (4) vitreous; and (5) optic nerve). FIG. 20B illustrates a slice from a three-dimensional CT images showing a position of the vitreous thermistor in one porcine eye.DETAILED DESCRIPTION

[0093] The present technology comprises ocular cooling devices for reducing and / or controlling an eye temperature level. The ocular cooling devices may be useful in methods including, but not limited to, treating or preventing hypoxic ocular damage, ischemic ocular damage, an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control. In some embodiments, the ocular cooling devices are portable.

[0094] While the present technology is capable of being embodied in various forms, the description below of several embodiments is made with the understanding that the present technology is to be considered as an exemplification of the present technology and is not intended to limit the present technology to the specific embodiments illustrated. Headings are provided for convenience only and are not to be construed to limit the present technology in any manner. Embodiments illustrated under any heading may be combined with embodiments illustrated under any other heading.Ocular Cooling Devices

[0095] The ocular cooling devices of the present technology comprise a contact ring that is sized and shaped to partially cover a subject’s eye. The contact ring may be coupled to a thermoelectric cooler, and the thermoelectric cooler may be coupled to a chamber. The ocular cooling devices may comprise tubes (e.g., an inlet tube or an outlet tube) or one or more power supply lines. The tubes may supply hot or cold gas or fluid that is exchanged in the chamber. The chamber may remove heat from a hot side of the thermoelectric cooler, which may assist in temperature control of the eye contact ring.Contact Rings

[0096] The ocular cooling devices of the present technology comprise contact rings that are sized and shaped to at least partially cover a subject’s eye. In some embodiments, the contact rings protect the subject’s eye from drying or from exposure to debris. The contact rings may comprise (i) a first side that contacts the subject’s eye and (ii) a second side opposite to the first side. In some embodiments, the contact ring is an eye cooling ring. The contact rings may distally extend past a coronal plane thatintersects with a limbus of the subject’s eye. A contact area between the contact ring and the subject’s eye may be anterior to a bulbus oculi equator of the subject’s eye.

[0097] The contact rings of the present technology may be coupled to a thermoelectric cooler. In some embodiments, the contact rings are coupled by p-type and n-type semiconductor pillars to the thermoelectric cooler. The p-type and n-type semiconductor pillars may be comprised within the thermoelectric cooler. In some embodiments, the p-type and / or n-type semiconductor pillars are in direct contact with at least a portion of the contact ring. The p-type and n-type semiconductor pillars may provide active temperature transfer within the ocular cooling devices.

[0098] In some embodiments, the contact rings comprise one or more flanges. At least a portion of an extraocular tissue of the subject’s eye may position over the flange of the contact ring (e.g., superior and inferior fornices beneath the eyelids). The extraocular tissue may be an eyelid, and at least a portion of the eyelid may close over the second side of the contact ring. The first side of the contact ring may increase a heat level drawn from the portion of the extraocular tissue positioned over the flange of the contact ring, relative to a control.

[0099] The contact rings may draw heat primarily from the surface in contact with the eye, and not from surfaces in contact with the eyelids or air. The surfaces not in contact with the eye may be insulated with a thin (e.g., about 75-500 pm) conformal coating of medical grade silicone (e.g., NuSil MED-6020, thermal conductivity 0.2 W / (m K)) or Parylene C (0.08 (W / (m K)). These thin coatings may reduce heat flow across non-target surfaces without significantly altering an outside dimension of the contact ring.

[0100] Radius of Curvature

[0101] The contact ring may comprise a radius of curvature selected for a size or shape of at least a portion of the subject’s eye. In some embodiments, the radius of curvature is at least about 2 mm to at least about 15 mm.

[0102] In some embodiments, the radius of curvature is at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, at least 10 mm, at least 11 mm, at least 12 mm, at least 13 mm, at least 14 mm, or at least 15 mm.

[0103] In some embodiments, the radius of curvature is about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, or about 15 mm.

[0104] In some embodiments, the radius of curvature is at least about 2 mm, at least about 3 mm, at least about 4 mm, at least about 5 mm, at least about 6 mm, at least about 7 mm, at least about 8 mm, at least about 9 mm, at least about 10 mm, at least about 11 mm, at least about 12 mm, at least about 13 mm, at least about 14 mm, or at least about 15 mm.

[0105] Thermal Conductivity & Materials

[0106] The contact ring may comprise or consist of one or more materials having a thermal conductivity level that is at least about 0.5W / (m*K) to at least about 2,000 W / (m»K). In some embodiments, the first side of the contact ring comprises or consists of one or more materials having a thermal conductivity level that is at least about 0.5W / (m*K) to at least about 2,000 W / (m*K). In some embodiments, the one or more materials having a thermal conductivity level that is at least about 0.5W / (m*K) to at least about 2,000 W / (m*K) is selected from the group consisting of a glass, a ceramic, a metal, an acrylic, a glass-ceramic, a copper, and a diamond. In some embodiments, the one or more materials having a thermal conductivity level that is at least about 0.5W / (m*K) to at least about 2,000 W / (m*K) comprises a thermally conductive additive (e.g., carbon nanotubes, graphite, aluminum powder, copper powder, aluminum oxide particles, silicon carbide particles). Such materials may comprise a thermal conductivity of at least about 25-30 W / (m K).

[0107] The contact ring may comprise or consist of one or more materials having a thermal conductivity level that is about 0.5W / (m»K) to about 2,000 W / (m»K). In some embodiments, the first side of the contact ring comprises or consists of one or more materials having a thermal conductivity level that is about 0.5W / (m*K) to about 2,000 W / (m»K).

[0108] The contact ring may comprise or consist of one or more materials having a thermal conductivity level that is at least 0.5W / (m»K) to at least 2,000 W / (m*K). In some embodiments, the first side of the contact ring comprises or consists of one or more materials having a thermal conductivity level that is at least 0.5W / (m*K) to at least 2,000 W / (m*K).

[0109] The contact ring may comprise one or more materials having a thermal conductivity level that is less than 1.0 W / (m»K) or less than 0.5 W / (m*K). In some embodiments, the second side of the contact ring comprises or consists of one or more materials having a thermal conductivity level that is less than 1 .0 W / (m*K) or less than 0.5 W / (m*K). In some embodiments, the one or more materials is a silicone.

[0110] In some embodiments, the contact ring or the second side of the contact ring comprises or consist of one or more materials having a thermal conductivity level that is less than about 1.0 W / (m*K), less than about 0.9 W / (m*K), less than about 0.8 W / (m»K), less than about 0.7 W / (m*K), less than about 0.6 W / (m»K), less than about 0.5 W / (m»K), less than about 0.4 W / (m*K), less than about 0.3 W / (m»K), less than about 0.2 W / (m*K), or less than about 0.1 W / (m*K).

[0111] In some embodiments, the contact ring or the second side of the contact ring comprises or consist of one or more materials having a thermal conductivity level that is less than at least 1 .0 W / (m»K), less than at least 0.9 W / (m»K), less than at least 0.8 W / (m»K), less than at least 0.7 W / (m»K), less than at least 0.6 W / (m»K), less than at least 0.5 W / (m*K), less than at least 0.4 W / (m*K), less than at least 0.3 W / (m*K), less than at least 0.2 W / (m«K), or less than at least 0.1 W / (m*K).

[0112] In some embodiments, the contact ring or the second side of the contact ring comprises or consist of one or more materials having a thermal conductivity level that is less than at least about 1 .0 W / (m»K), less than at least about 0.9 W / (m*K), less than at least about 0.8 W / (m»K), less than at least about 0.7 W / (m»K), less than at least about 0.6 W / (m»K), less than at least about 0.5 W / (m»K), less than at least about 0.4 W / (m*K), less than at least about 0.3 W / (m«K), less than at least about 0.2 W / (m*K), or less than at least about 0.1 W / (m*K).

[0113] The contact rings may comprise or consist of a non-transparent or an opaque material. In some embodiments, the contact rings comprise a metal. The contact rings may comprise or consist of a solid or homogenous material.

[0114] In some embodiments, the contact rings comprise or consist of a transparent or translucent material. Nonlimiting examples of such materials include a glass, a transparent ceramic, a polycarbonate, and an acrylic.

[0115] Sensors, Electrodes, and Ocular Cooling Device Control

[0116] In some embodiments, the contact rings of the present technology further comprise one or more sensors or one or more electrodes. The one or more sensors may comprise a pressure sensor, a temperature sensor, or an optical sensor. The one or more sensors or one or more electrodes may sense one or more biomarkers or one or more biopotentials from a surface of the subject’s eye.

[0117] In some embodiments, the temperature sensor comprises a thermistor.

[0118] The one or more sensors or one or more electrodes may contact at least a portion of the subject’s eye and / or may be used as an input to a control circuit or computational model. A measurement, such as a temperature measurement, of at least a portion of the subject’s eye may be collected by the one or more sensors or the one or more electrodes. The measurement may be used as input for a model, lookup table, or equation relating to the measurement, thereby generating an output based on the portion of the subject’s eye. The output may be compared to a preferred measurement versus time profile. An error value or otherwise difference between the measurement and the preferred measurement may be calculated. A current through the optical cooling device or the thermoelectric cooler thereof may be adjusted to reduce the error value or the difference. In some embodiments, adjusting the error value or the difference is used to control the temperature, the pressure, or another optical parameter of at least a portion of the subject’s eye, for example, a retina temperature. In some embodiments, the ocular cooling device design and or a cooling protocol optimization thereof may be guided by the control circuit or the computational model, thereby modulating heat flow in the eye or from the eye.

[0119] The control circuit or the computational model may monitor a temperature of the contact ring via a temperature sensor (e.g., thermistor) comprised within the contact ring. In use, the temperature at this location may be related to temperature at different locations throughout the eye based on knowledge gained from in vitro and in vivo measurements and from the thermal models. A control algorithm may relate the inferred temperature at key locations in the eye to the target temperatures at these locations, and adjust the thermoelectric cooler current accordingly, where heat flow across the thermoelectric cooler is proportional to current. Current may be controlled via a controller (e.g., commercial H-bridge controller; Maxim MAX1968, provides + / - 3Awith 0.1 °C temperature control) that receives analog input from the control algorithm. The algorithm may be implemented to allow for optimal initial cooling profiles, and temperature maintenance feedback functions, to be derived.

[0120] A thermal time constant of the eye or the ocular cooling device may be evaluated during in vitro and / or in vivo testing, and a feedback control level may be damped accordingly. A performance of the ocular cooling device may also be evaluated in different ambient temperatures (0-100°C) using the in vitro testing system inside of walk-in environmental chambers. Optimized feedback control algorithms may ultimately be programmed into a dedicated microprocessor for direct / indirect control during use of the ocular cooling devices.

[0121] In some embodiments, initial eye temperature measurements are made with constant currents powering the thermoelectric coolers, and later measurements may test the feedback control algorithms. Temperature profiles with normal, and partial, central retinal artery perfusion may be obtained.

[0122] In vivo measurements of temperature vs. time may be performed in instrumented eyes. In some embodiments, temperature profiles are recorded with constant current thermoelectric cooler activation, which may be used to refine computational models to reflect desired conditions. Temperature profiles recorded with feedback control of the thermoelectric coolers may be used to drive refinement the feedback control algorithm.

[0123] Various current vs. time profiles and feedback strategies may be used and optimized to reach and / or maintain desired temperatures in target tissues, without overcooling tissues in direct contact with the contact ring.

[0124] Contact Ring Design

[0125] The contact rings of the present technology may be designed to maximize a heat flow level from a subject’s eye. The contact rings may be designed for one or more of: (i) maximizing a contact area with the subject’s eye, (ii), maximizing a contact area with the thermoelectric coolers, or (iii) maximizing a thermal conduction level between the eye and the thermoelectric coolers via the contact rings.

[0126] Maximizing thermal conduction between the eye and the thermoelectric cooler may be accomplished by maximizing a cross-sectional area of the contact ringin directions perpendicular to heat flow while minimizing bulk (e.g., weight) of the contact ring. A corresponding circular recess may be machined into an underside of the contact ring to allow a press-fit of a contact lens into the contact ring, which may be sealed with medical grade silicone or cyanoacrylate adhesive. This modular design approach may also allow for simple replacement of the contact lens between animals or patients, as well as trial of multiple lens shapes during development.Thermoelectric Coolers

[0127] The ocular cooling devices of the present technology may comprise one or more thermoelectric coolers. The one or more thermoelectric coolers may assist in temperature control of the contact ring and / or of a subject’s eye. The thermoelectric coolers may be coupled to the contact ring and / or to a chamber. In some embodiments, the thermoelectric coolers comprise a cold side coupled to the contact ring and a hot side opposite to the cold side. In some embodiments, the cold side is coupled to a second side of the contact ring.

[0128] The cold side of the thermoelectric coolers may be coupled to the hot side of the thermoelectric cooler. The cold side and the hot side may be coupled by p-type and n-type semiconductor pillars.

[0129] The thermoelectric coolers may be coupled to a contact ring or a chamber. The thermoelectric cooler may be coupled to the contact ring or to the chamber with a thermally conductive adhesive, a locking mechanism, or a ferrous material (e.g., a magnet). In some embodiments, the thermoelectric coolers are fabricated such that the contact rings form a cold side substrate, with the p-type and n-type semiconductor pillars fabricated directly on the contact ring.

[0130] In some embodiments, the ocular cooling devices of the present technology comprise a first thermoelectric cooler and a second thermoelectric cooler. A contact ring may be coupled by p-type and n-type semiconductor pillars to a cold side of the first thermoelectric cooler. The second thermoelectric cooler may comprise a cold side that is coupled to a hot side of the first thermoelectric cooler. When the ocular cooling device comprises more than one thermoelectric coolers, the thermoelectric coolers may be oriented thermally in series.

[0131] The thermoelectric coolers of the present technology may comprise one or more power supply lines. The one or more power supply lines may provide power to the thermoelectric cooler. In some embodiments, the one or more power supply lines comprise power wires and temperature sensing wires, which may be routed together to a housing containing a power supply or a control circuit located near the ocular cooling device (e.g., about 30-50 cm from the subject’s eye).

[0132] The thermoelectric cooler may comprise a maximum heat flow within acceptable size limits and power availability (e.g., < 5A to achieve sufficient heat flow).Chambers

[0133] The ocular cooling devices of the present technology may comprise chambers that assist in temperature control and or temperature exchange of one or more portions of the ocular cooling devices and / or of a subject’s eye. The chambers may be coupled to a thermoelectric cooler (e.g., coupled to a hot side of the thermoelectric cooler) or the contact ring. In some embodiments, the chambers comprise one or more tubes (e.g., an inlet tube or an outlet tube). The one or more tubes may provide entry or exit of fluid or gas in the chamber.

[0134] I n some embodiments, the cham ber is a heat exchanger. The chamber may allow for fluid or gas at two or more temperatures to enter or exit the ocular cooling device. Hot or cold fluid or gas may enter the chamber through the inlet tube and may exit the chamber through the outlet tube. In some embodiments, the inlet tube allows for inlet of a cold fluid or a cold gas into the chamber. In some embodiments, the outlet tube allows for outlet fluid or a gas from the chamber that is warmer than a fluid or a gas entering the chamber.

[0135] The ocular cooling devices may comprise a heat sink. In some embodiments, the chamber comprises or consists of a heat sink. In some embodiments, the heat sink is used in place of a chamber. The heat sink may be thermally coupled to the contact ring or to the hot side of the thermoelectric cooler. In some embodiments, the heat sink is a finned heat sink. The heat sink may provide passive temperature exchange from the ocular cooling device.Central Void

[0136] In some embodiments, one or more of the contact ring, the thermoelectric cooler, or the chamber comprises a central void. The central void may comprise or consist of an annular shape. At least a portion of the subject’s eye may be visible or viewed through the central void. In some embodiments, at least a portion of a sclera (e.g., an anterior sclera), a cornea, a pupil, or a retina of the subject’s eye is visible through the central void.

[0137] The central void may comprise a light penetrable window. The light penetrable window may comprise a transparent window or a translucent window. In some embodiments, the light penetrable window comprises a glass, an acrylic, a polycarbonate, or a transparent ceramic. In some embodiments, the light penetrable window comprises a lens. In some embodiments, the central void comprises a diameter of at least about 5 mm to at least about 15 mm.

[0138] In some embodiments, the light penetrable window provides thermal insulation between at least a portion of the eye and the environment surrounding the ocular device. The light penetrable window may be designed to vault over a cornea, trapping a relatively thick (about 200-400 microns) tear film. This may provide corneal protection even when corneal abrasions are present. The light penetrable window may comprise a scleral contact lens with corneal diameter and base curve high enough to accommodate eyes or various sizes, and with an outside diameter no more than 2mm larger than the corneal diameter, may be used in some embodiments.

[0139] In some embodiments, the central void comprises a diameter of at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, at least 10 mm, at least 11 mm, at least 12 mm, at least 13 mm, at least 14 mm, or at least 15 mm.

[0140] In some embodiments, the central void comprises a diameter of about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, or about 15 mm.

[0141] In some embodiments, the central void comprises a diameter of at least about 5 mm, at least about 6 mm, at least about 7 mm, at least about 8 mm, at least about 9 mm, at least about 10 mm, at least about 11 mm, at least about 12 mm, at least about 13 mm, at least about 14 mm, or at least about 15 mm.Housing

[0142] The ocular cooling devices of the present technology may be connected to a housing. In some embodiments, one or more of the inlet tube, the outlet tube, the one or more power supply lines, or one or more sensor data lines connect the ocular cooling device to a housing. The housing may comprise one or more of a pump, a power supply, a heat dissipating component, a signal processing circuit, a control circuit, a microprocessor, or a rectifier. The rectifier may convert an alternating current (AC) to a direct current (DC) and / or may power the pump or the thermoelectric cooler. The heat dissipating component may comprise a chemical cold pack, an ice bath, a heat sink (e.g., a finned heat sink), or a heat pump. The heat pump may comprise or consist of a second thermoelectric cooler. In some embodiments, the heat dissipating component is a convection-based heat dissipating component.

[0143] For each chamber, the thermoelectric cooler current required to maintain a target temperature within the surrogate eye may be determined, as can the time required to reach the target temperature. Each of these measures may reflect the heat transfer efficiency between the thermoelectric cooler and chamber. The temperature of the circulating fluid or gas entering and leaving the chamber may be monitored via one or more temperature sensors (e.g., thermistors). This may be carried out at a constant flow rate or at a constant temperature.

[0144] The pump may comprise a fluid or a gas. The fluid or the gas may be transported by an inlet tube or an outlet tube of the ocular cooling device.

[0145] The heat dissipating components may comprise a chamber channel. The chamber channel may comprise turbulence-creating dimples, comprising protrusions in the upper and lower surfaces of the chamber channel. The dimples may disrupt laminar flow patterns of liquid or gas to mix the boundary layer with the bulk fluid and enhance heat transfer, relative to a baseline (e.g., up to 84%). This may reduce the required bulk flow, so that inlet and outlet tubing diameter is minimized (to achieve a flexible, low-bulk system) and pump requirements are reduced (power and size). In some embodiments, the heat dissipating component reduces a heat of circulating fluid or gas. The circulating fluid may be deionized water, polyethylene glycol, or a mix of deionized water and polyethylene glycol in any relative proportion.

[0146] The warmed water from the chamber may be conveyed via flexible (e.g., Tygon) tubing to the heat dissipating component site: an ice bath ora standard chemicalcold pack within a housing. In each case, a heat exchanger may be used to ensure that the heat is effectively transferred to the cold pack or an ice bath, and that the fluid returning to the chamber has reached thermal equilibrium with the cold pack or ice bath. In some embodiments, the chambers are fabricated without dimples or protrusions or fins, or with two or more dimple or protrusion or fin patterns.

[0147] In some embodiments, the heat dissipating system comprises removing heat from a hot side of the thermoelectric coolers to maintain sufficient heat flow from the eye into a cold side of the thermos electric coolers via the contact ring. The heat dissipating system may comprise a compact fluid system that disposes of heat in cold packs.

[0148] The housing may be powered by standard rechargeable lithium ion batteries with 2 A hr capacity (0.50-0.75kg) or by any means sufficient to power the thermoelectric cooler, the pump, and / or a feedback control circuitry for a period of time required to carry out one or more methods of the present technology.

[0149] In some embodiments, the housing is portable. In some embodiments, the housing is positioned to be worn by the subject. The housing may comprise or consist of a chest pack.

[0150] The insulated pouch containing the cold pack may be located for attachment of a battery or a control circuit housing. This assembly may be affixed at any convenient location on the patient via a high-strength adhesive pad (peel and stick) or hook-and-loop strap, or the like. An entire binocular system, including battery, may weigh approximately 1 kg and occupy no more than a 15x20x8 cm volume (about the volume of three standard chemical cold packs).Optimization and Evaluation

[0151] The ocular cooling devices of the present technology may be optimized to achieve desired eye cooling profiles. Eye tissues may be evaluated after eye cooler application to healthy eyes for baseline evidence to establish parameters that avoid over-cooling of one or more portions of the eye (e.g., the sclera) in direct contact with the contact rings. For example, paraffin-stained histological sections of retina and anterior eye, TUNEL, GFAP, and retinal ganglion cell counts on cryosections, and Western blotting and real time PCR on retinal homogenates for inflammatory and celldeath mediators may also be used in establishing the baseline parameters. In some embodiments, the ocular cooling devices of the present technology are optimized or adjusted using a model disclosed in Gongal, D et al. “Thermal finite element analysis of localized hypothermia treatment of the human eye.” Medical engineering & physics vol. 111 (2023): 103928, the entire contents of which is incorporated herein by reference in its entirety.

[0152] The physiological effects of the ocular cooling devices in the presence of retinal ischemia due to central retinal artery occlusion (CRAO) may be evaluated. This may be accomplished by endovascular occlusion of the ophthalmic artery. Nonlimiting outcome measures include electroretinography (ERG), visual evoked potential (VEP), pupillometry, and evaluation of blood-retinal barrier permeability. In some embodiments, a new full-field pattern ERG system capable of probing discrete areas of the central and peripheral retina may be used to objectively monitor regional functional changes of the retinal ganglion cells over the entire anatomical retina.

[0153] The physiological effects of the ocular cooling devices may be assessed in the presence of traumatic optic nerve injury, such as nerve crush or the like. To this end, a surgical procedure may include a lateral approach that exposes the optic nerve, which is then subjected to controlled crush injury.

[0154] The physiological effects of the ocular cooling devices in the presence of traumatic blast injury may be evaluated. For example, a blast tube injury model may be developed to assess optical cooling immediately after injury.Methods

[0155] The present technology comprises methods of reducing an eye temperature level in a subject in need thereof relative to a control and reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control. The methods comprise positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject. In some embodiments, the method reduces or prevents the ocular pain, the ocular inflammation, or the intraocular pressure during or after an ocular procedure (e.g., an intraocular injection).

[0156] In some embodiments, the present technology comprises methods of treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof. The methods may reduce an eye temperature level of a subject to provide neuroprotection. The methods comprise positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject. In some embodiments, the optic nerve injury comprises a traumatic optic nerve injury (e.g., blast or blunt trauma). In some embodiments, the retinal ischemia comprises a retinal ischemia from central retinal artery occlusion (CRAO), non-arteritic ischemic optic neuropathy (NAION), retinal detachment, or ocular trauma.

[0157] In some embodiments, the present technology comprises methods of reducing or preventing a vision loss in a subject’s eye, relative to a control. In some embodiments, the vision loss comprises permanent vision loss. The methods comprise positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject.

[0158] In some embodiments, the methods comprise providing local hypothermia to delay the progression of an eye injury and or vision loss. The methods may be implemented during or after a hypoxic brain injury or head trauma.

[0159] In some embodiments, the period of time in the methods of the present technology is about 2 minutes to about 24 hours. In some embodiments, the period of time is about 2 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 16 hours, about 20 hours, or about 24 hours.

[0160] In some embodiments, the period of time in the methods of the present technology is at least 2 minutes to at least 24 hours. In some embodiments, the period of time is at least 2 minutes, at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 4 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours.

[0161] In some embodiments, the period of time in the methods of the present technology is at least about 2 minutes to at least about 24 hours. In some embodiments, the period of time is at least about 2 minutes, at least about 5 minutes, at least about 10 minutes, at least about 20 minutes, at least about 30 minutes, at least about 1 hour,at least about 2 hours, at least about 4 hours, at least about 8 hours, at least about 12 hours, at least about 16 hours, at least about 20 hours, or at least about 24 hours.

[0162] In some embodiments, the methods of the present technology are performed in vivo, in vitro, or ex vivo.

[0163] In some embodiments, the control comprises the subject at baseline.

[0164] In some embodiments, the subject of the methods of the present technology may comprise a mammalian subject or an eye or ocular tissue thereof. In some embodiments, the subject is human. In some embodiments, the subject is a porcine subject.

[0165] The ocular cooling devices or the methods of the present technology may reduce a temperature level in one or more of a retina, a vitreous, a posterior pole, or a proximal optic nerve of the subject’s eye. The temperature level in the subject’s eye may be reduced from anterior to posterior positions. In some embodiments, the ocular cooling device or the method cools at least a portion of the subject’s eye to greater than about 4°C to less than 35°C.

[0166] In some embodiments, the ocular cooling devices or the methods of the present technology cool at least a portion of the subject’s eye to about 35°C, about 34°C about 32°C, about 30°C, about 28°C, about 26°C, about 24°C, about 22°C, about 20°C, about 18°C, about 16°C, about 14°C, about 12°C, about 10°C, about 8°C, about 6°C, about 5°C, or about 4°C.

[0167] In some embodiments, the ocular cooling devices or the methods of the present technology cool at least a portion of the subject’s eye to at least 35°C, at least 34°C at least 32°C, at least 30°C, at least 28°C, at least 26°C, at least 24°C, at least 22°C, at least 20°C, at least 18°C, at least 16°C, at least 14°C, at least 12°C, at least 10°C, at least 8°C, at least 6°C, at least 5°C, or at least 4°C.

[0168] In some embodiments, the ocular cooling devices or the methods of the present technology cool at least about a portion of the subject’s eye to at least about 35°C, at least about 34°C at least about 32°C, at least about 30°C, at least about 28°C, at least about 26°C, at least about 24°C, at least about 22°C, at least about 20°C, at least about 18°C, at least about 16°C, at least about 14°C, at least about 12°C, at leastabout 10°C, at least about 8°C, at least about 6°C, at least about 5°C, or at least about 4°C.

[0169] In some embodiments, an ophthalmic ointment or sodium caboxymethylcellulose-containing ophthalmic solution is be applied to the eye prior to positioning the contact ring onto the subject’s eye.EXAMPLESExample 1 : Exemplary Ocular Cooling Device

[0170] An exemplary ocular cooling device configured in accordance with the embodiments of the present technology is illustrated in FIGS. 1A-1 I (“ocular cooling device 100”). More specifically, FIG. 1A is an angled planar view of ocular cooling device 100 comprising contact ring 101 positioned on an eye. FIGS. 1 B, 1C, 1 E, and 1 F illustrate side profile views of ocular cooling device 100. FIG. 1 D illustrates a planar view of ocular cooling device 100. As shown in FIGS. 1A-1 F, contact ring 101 is coupled to thermoelectric cooler 102. Thermoelectric cooler is coupled to chamber 105, which comprises inlet and outlet tubes 104 for the inlet of cold fluid or gas and the outlet of a fluid or gas that is warmer than a fluid or gas entering the chamber, and power supply lines 103 that power the thermoelectric cooler. Chamber 105 may comprise a convective heat exchanger containing flowing fluid. The ocular cooling device further comprises central void 106, which provides an open center for an unobstructed view of at least a portion of the eye, such as a cornea or a pupil. In FIG. 1 F, ocular cooling device 101 is in use by a subject, wherein contact ring 101 is positioned over the eye of the subject, and the subject’s eyelid closes over flange 118A and / or flange 118B of the contact ring.

[0171] FIG. 1 G and 1 H. illustrate contact ring 101 with central void 106 comprising window 107 and junction 108 between window 107 and contact ring 101. Window 107 may be a light penetrable window that permits light to enter the eye and allows observation of the eye (e.g., the pupil) when the contact ring is positioned on the eye. FIG. 11 illustrates a planar view of ocular cooling device 101 comprising window 107. I

[0172] FIG. 2A illustrates contact ring 101 coupled to thermoelectric cooler 102. Thermoelectric cooler 102 may be fabricated such that contact ring 101 forms a cold side substrate. Alternatively, thermoelectric cooler 102 may comprise a cold sidesubstrate that was coupled to contact ring 101 using, for example, a thermally conductive adhesive. A hot side of thermoelectric cooler may be exposed to the surrounding environment of ocular cooling device 100. FIG. 2B illustrates contact ring 101 coupled to the cold side of a first thermoelectric cooler 102B, and a second thermoelectric cooler 102A with its cold side coupled to a hot side of the first thermoelectric cooler 102B. When ocular cooling device 100 comprises more than one thermoelectric coolers, the more than one thermoelectric coolers may be placed thermally in series.

[0173] FIGS. 2C-2F illustrate thermoelectric cooler 102 comprising semiconductor pillars 120. Semiconductor pillars 120 are p-type and n-type semiconductor pillars deposited between contact ring 101 and an upper plate 119 (FIG. 2C and 2E). Alternatively, semiconductor pillars 120 may be deposited directly on contact ring 101 (FIG. 2D and 2F). Contact ring 101 may serve as a cold side substrate, and thermoelectric cooler 102 may comprise upper plate 119, which is a hot side substrate.

[0174] FIG. 3 illustrates ocular cooling device 100 comprising contact ring 101 coupled to chamber 105, through which cooled fluid or gas may flow. The fluid or gas may be exchanged or delivered through the inlet or outlet tubes 104. Chamber 105 may form a hollow ring that is coupled to contact ring 101. A bottom wall of chamber 105 may be formed by a top surface of contact ring 101. Ocular cooling device 100 may further comprise opening 109 in chamber 105, which is an opening within chamber 105 through which fluid or gas flows.

[0175] FIGS. 4A-4D illustrate ocular cooling device 100 further comprising heat sink 110. Heat sink 110 may be coupled to contact ring 101 (FIG. 4B) or to thermoelectric cooler 102 (FIGS. 4C and 4D). FIGS. 4A-4D depict heat sink 110 as a finned heat sink for heat dissipation to the surrounding air of ocular cooling device 100 or to a flow of cooled fluid or gas that is directed at heat sink 110. Heat sink 110 may be a feature of contact ring 101 or may be a separate component that is coupled to contact ring 101 , for example, using a thermally conductive adhesive.

[0176] FIGS. 5A and 5B illustrate contact ring 101 of ocular cooling device 100 further comprising temperature sensor 111. Contact ring 101 may comprise temperature sensors within voids of contact ring 101 (e.g., temperature sensor 1 11A-111 C). Temperature sensor 101 may be used to monitor the temperature of contact ring 101 and may be used as input to a control circuit or computational algorithm.

[0177] FIG. 6A illustrates ocular cooling device 100 comprising magnets 112A and 112E3 that join contact ring 101 to thermoelectric cooler 102. FIGS. I B and 1 C illustrate planar views of ocular cooling device 100 of FIG. 6A, comprising magnets 112A-112C. Magnets 112A-1 12C are attached to thermoelectric cooler 102 and contact ring 101. Magnets 112A-112C may be substituted for other ferrous material in corresponding locations, potentially within recesses of contact ring 101 or thermoelectric cooler 102. This configuration allowed contact ring 101 to be readily replaced between subjects or for a contact ring of an optimal size and shape to be selected for a given subject and attached to thermoelectric cooler 102 prior to use.

[0178] FIGS. 7A and 7B illustrate an additional locking mechanism for ocular cooling device 100, where contact ring 101 comprises recesses 1 13A and 113B which accept locking tabs 114A and 114B on thermoelectric cooler 102. This configuration allowed contact ring 101 to be readily replaced between subjects or for a contact ring of an optimal size and shape to be selected for a given subject and attached to thermoelectric cooler 102 prior to use.

[0179] FIG. 8 illustrates contact ring 101 of ocular cooling device 100, further comprising electrode 115. Electrode 115 may be used to sense biopotentials from the surface of an eye. Electrode 115 may be operatively connected to an external signal processing component. Electrode 115 may be a ring-shaped electrode contained within contact ring 101 and with at least a portion of electrode 115 exposed to make contact with an eye surface when contact ring 101 is positioned on a subject’s eye.

[0180] FIGS. 9A-9D illustrate contact ring 101 of ocular cooling device 100, further comprising sensors 116A-116E on contact ring 101. Sensors 1 16A-116E may be located in recesses formed in contact ring 101. Sensors 1 16A-116E may be pressure or optical sensors, or a combination thereof. Sensors 116A-116E may be positioned to contact ocular tissues or extraocular tissued when contact ring 101 is positioned on a subject’s eye. Sensors 116A-116E may be positioned on a proximal surface of contact ring 101 . In this position, sensors 116A-116E may contact an eye surface when contact ring 101 is placed on the subject’s eye.

[0181] FIG. 10 illustrates layer 117 on contact ring 101 of ocular cooling device 100. Layer 117 contacts an extraocular tissue (e.g., eyelid) when contact ring 101 is positioned on a subjects eye and coats a surface of contact ring 101 that does not contact the eye. Layer 117 may have a thermal conductivity level of less than 0.5W / (m- K). The portion of contact ring 101 beneath layer 117 may comprise or consist of a material having a thermal conductivity level of greater than or equal to 0.5W / (m K), where layer 117 is less thermally conductive. Layer 117 may be an insulative layer, which increases the heat drawn from the eye by decreasing the heat drawn from extraocular tissues that come into contact with contact ring 101 .

[0182] FIGS. 11A and 11 B illustrate ocular cooling device 100 connected to connector 200 when ocular cooling device is positioned on a subject’s eye. Connector 200 may comprise tubes and wires that connect ocular cooling device 100 to housing 300. FIGS. 1 1A and 11 B illustrate housing 300 as a chest pack, where ocular cooling device 100 and housing 300 are wearable. The chest pack may comprise a pump, a power supply, heat dump, signal processing circuit, control circuit, microprocessor, or a gas or fluid cooling component.

[0183] FIGS. 12A and 12B illustrate ocular cooling device 100 being used by a subject. Ocular cooling device is positioned on the subject’s eye and is joined to housing 300 by connector 200. Housing 300 is illustrated as a non-wearable device. Housing 300 may be stationary or mobile. Connector 200 powers ocular cooling device 100 and comprises tubes that carry fluid or gas to and from ocular cooling device 100 and data lines that carry information from sensors in ocular cooling device 100. Housing 300 contains a pump, heat dissipating components, signal processing circuit, control circuit, microprocessor and an AC to DC converter. The AC to DC converter may power the pump and thermoelectric cooler 102 of ocular cooling device 100. The AC to DC converter is powered by a main power source via outlet 400.

[0184] FIG. 13 illustrates a method for controlling a retinal temperature level when ocular cooling device 100 is positioned on a subject’s eye. A desired retina cooling profile may be achieved by continuous adjustment of a current through thermoelectric cooler 102 in response to one or more measurements made at contact ring 101 using temperature sensors 111A-111 C (FIGS. 5A and 5B), electrode 115 (FIG. 8), or sensors116A-116E (FIGS. 9A-9D). The method uses a relationship between contact ring 101 temperature and a retinal temperature.Example 2: In Vitro Assessment of Ocular Cooling Device in Porcine Eye

[0185] To assess cooling in an ocular model, ocular cooling devices in accordance with the embodiments of the present technology were assessed in vitro using an isolated porcine eye. Fresh porcine eyes were harvested with at least 13mm of optic nerve attached.

[0186] The ocular cooling devices comprised an aluminum cooling contact ring in contact with the sclera (390mm2contact area, cornea not contacted or obstructed through a 14mm diameter central void). Three embedded thermistors monitored the temperature in anterior, equatorial, and posterior locations within the scleral wall (FIG. 14A). With the portion of the eye that is surrounded by extraocular muscles and other tissues in situ immersed in a warm oil bath at 37°C to stimulate ocular tissues. The posterior sclera was cooled 6-10°C while the tissues in contact with the cooling ring remained above 0°C (FIG. 14B). Intraocular pressure was maintained at 15.2 mmHg using a 27Ga needle inserted through the cornea into the anterior chamber, connected to a bag of phosphate-buffered saline suspended 21 cm above the eye level.

[0187] The scleral contact ring transitioned from an initial holding temperature near 34.5°C (typical temperature of exposed anterior eye surface) to 4°C in approximately two minutes. The 4°C temperature was chosen as a minimum safe temperature that would both provide maximum cooling of deeper eye tissues and avoid risk of hypothermic damage, as it is commonly employed for preservation of donor tissues prior to transplant and has been used for deep hypothermic treatment of optic nerve. This demonstrated that the ocular cooling device is capable of cooling the eye from anterior to posterior tissues.

[0188] Ocular cooling device design and cooling protocol optimization may be guided by a computational model of heat flow in the eye. To this end, high-resolution magnetic resonance imaging (MRI) images of the porcine eyes and computed tomography (CT) images of eyes with thermistors were acquired to generate preliminary pig and human ocular models (FIGS. 18A-18D). Thermistors may create artifacts in MRI, thus MRI was used to determine the detailed morphology of each eye tested, while post-experiment CT was used to locate all thermistors. MRI and CT images weremerged, and thermistor locations were transferred to the model for comparison to empirical temperature versus time data.

[0189] Five target thermistor positions were assessed next using the porcine eye model of FIGS. 18A-18D (n=5). For each target thermistor position (Table 1 , columns in table), the (x,y,z) coordinates of that thermistor in all five eyes was determined from CT images. The average coordinates across the five eyes were determined. The distance from the average coordinates for each individual thermistor are shown in the table below. On average, thermistors were located within 1 .2 mm of the target position.

[0190] For each thermistor position (Table 2, columns in table), a difference measure, root mean square error, (RMSE) was calculated between the measurements made in one eye and the average of measurements made across all five eyes (FIG. 15, FIGS. 16A-16F, and FIGS. 17). For each thermistor position, the Min, Max and Average RMSE values were determined.Table 1 : Variation in thermistor location.Distance from Average Position (mm)Anterior Equatorial Posterior OpticVitreousSclera Sclera Sclera Nerve x 0.4 0.4 0.5 4.7 2.2Eye 1 y 1.0 1.5 2.7 0.1 0.5 z 1.7 0.5 0.3 0.5 0.2 x 0.4 0.3 0.6 4.5 1.2Eye 2 y 2.0 0.8 0.2 0.4 0.3 z 1.5 0.2 0.1 2.0 0.5 x 0.3 1.4 0.3 1.5 0.5Eye 3 y 3.2 0.9 2.1 2.3 2.5 z 0.9 0.1 0.6 2.3 0.3 x 0.2 0.3 0.2 3.9 1.2Eye 4 y 0.4 1.8 2.5 0.3 0.0 z 2.1 0.2 1.0 1.6 0.4 x 0.4 1.3 1.2 3.7 0.7Eye 5 y 0.2 0.2 1.8 2.2 2.8 z 1.0 0.6 1.9 1.4 0.20.3 0.7 0.6 3.7 1.2 x (0.1) (0.6) (0.4) (1.3) (0.7)Average 1.4 1.0 1.9 1.1 1.2(SD)y(1.2) (0.6) (1.0) (1.1) (1.3)1.4 0.3 0.8 1.6 0.3(0.5) (0.2) (0.7) (0.7) (0.1)Table 2: Repeatability of temperature measurements across eyes.RMSE of temperatureCONTACT Anterior Equatorial Posterior OpticVitreousRING Sclera Sclera Sclera NerveMin 0.19 0.46 0.36 0.96 1.13 0.59Max 0.38 6.41 4.25 3.07 4.36 2.00Average 0.31 2.76 1.84 1.63 2.78 1.03RMSE%* 1.09 11.29 19.39 16.58 23.87 28.85* Bottom row expresses the average RMSE value as a percentage of the maximum temperature difference observed at that thermistor position.

[0191] RMSE as a percentage of the mean change in temperature at each thermistor location was determined using the following calculation: 100Example 3: Assessing Heat Dissipating Components of the Ocular Cooling Devices

[0192] Efficacy of heat dissipating components were assessed in conjunction with the ocular cooling devices of the present technology. Early testing determined that passive heat dissipating components were not sufficient to achieve rapid and stable cooling of the eye, especially when ambient air temperatures were elevated above typical room temperature. A simple convection-based heat dissipating component was found to be effective. A compact chamber was designed, machined, and bonded (via thermal epoxy) to the thermoelectric cooler hot side. A compact pump (1 L / min) circulated water through the block, the outflow was directed to an insulated pouch containing a standard chemical cold pack. The circulating water picked up heat fromthe thermoelectric cooler and disposed of it in the cold pack. This system provided effective heat disposal for over one hour.Example 4: Optimization of a control algorithm to rapidly achieve and maintain therapeutic temperatures.

[0193] An exemplary eye cooler control algorithm is configured to control the thermoelectric cooler current, which in turn determines the rate of heat removal from the eye. The goal is to bring eye tissues to neuroprotective temperatures as rapidly as possible without overcooling, and to maintain those temperatures indefinitely. Cooling of the posterior pole of the eye is critical, to preserve cells of the macula and optic nerve proximal to the retina. Therefore, goal of the control algorithm is to minimize the difference between the actual and desired temperature at the posterior pole.

[0194] From the in vitro and in vivo experiments, and the computational models, the spatiotemporal relationship between contact ring temperature and temperature at the posterior pole will be well understood. A transfer function relating the contact ring sensor temperature to the temperature at any location within the eye will be obtained by fitting the results of a series of model simulations.

[0195] It is anticipated that for a step change in CONTACT RING temperature, the posterior pole temperature (Tpp) was described with an over-damped second-order function defined by a long thermal time constant ( T ) and nonlinear gain (kWhere k = f (Tpp-7^ , time) ,= damping factor (>1), and a>n= undamped natural frequency.

[0196] The long thermal time constant will limit the rate of temperature change at the posterior pole. The goal of the algorithm will be a step (ideal) (e.g., from normal body temperature to 30°C) in posterior pole temperature, followed by maintenance of the new temperature (+ / - 1 °C), with the constraint that the sclera in contact with the contact ring is always >4°C. This will be achieved via a simple feedback algorithm implemented in LabView, for example, where the analog voltage at the input pin of the current controller is a function of the temperature of the feedback sensor and time. Theinitial cooling phase of the control profile can require maximum safe currents. This will be followed by a transition phase determined by the thermal time constant of the eye, and finally a maintenance phase to hold the eye tissues at the desired temperature.

[0197] Once an optimal cooling profile and control algorithm have been determined using the model, it will be validated both in vitro and in vivo using instrumented eyes. Critical measurements will be at the sclera in contact with the contact ring (to monitor for over-cooling) and at the posterior pole (to monitor the temperature change profile) via implanted thermistors.Additional Embodiments

[0198] The present technology includes, but is not limited to, the following specific embodiments set forth herein below in paragraphs

[0199] -

[0271] :

[0199] 1. An ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0200] 2. A method of reducing an eye temperature level in a subject in need thereof relative to a control, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce the eye temperature level in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0201] 3. Use of an ocular cooling device for reducing an eye temperature level in a subject in need thereof relative to a control, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce the eyetemperature level in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0202] 4. A method of reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0203] 5. Use of an ocular cooling device for reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0204] 6. The method or the use of embodiment 4 or 5, wherein the method or the use reduces or prevents the ocular pain, the ocular inflammation, or the intraocular pressure during or after an ocular procedure.

[0205] 7. The method or the use of embodiment 6, wherein the ocular procedure comprises an intraocular injection.

[0206] 8. The method or the use of any one of embodiments 2-7, wherein the control comprises the subject at baseline.

[0207] 9. A method of treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0208] 10. Use of an ocular cooling device for treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

[0209] 11 . The method or the use of embodiment 9 or 10, wherein the optic nerve injury comprises a traumatic optic nerve injury.

[0210] 12. The method or the use of embodiment 9 or 10, wherein the retinal ischemia is a retinal ischemia from central retinal artery occlusion (CRAO), non-arteritic ischemic optic neuropathy (NAION), retinal detachment, or ocular trauma.

[0211] 13. The method or the use of any one of embodiments 2-12, wherein the method or the use is performed in vivo.

[0212] 14. The ocular cooling device, the method, or the use of any one of embodiments 1 to 13, wherein the ocular cooling device is a portable ocular cooling device.

[0213] 15. The ocular cooling device, the method, or the use of any one of embodiments 1 to 14, wherein the contact ring is coupled by p-type and n-type semiconductor pillars to the thermoelectric cooler.

[0214] 16. The ocular cooling device, the method, or the use of any one of embodiments 1 to 15, wherein the thermoelectric cooler is coupled to the chamber.

[0215] 17. The ocular cooling device, the method, or the use of embodiment15 or 16 wherein the thermoelectric cooler is coupled to the contact ring or to the chamber with a thermally conductive adhesive, a locking mechanism, or a magnetic force.

[0216] 18. The ocular cooling device, the method, or the use of embodiment17, wherein the magnetic force comprises a ferrous material.

[0217] 19. The ocular cooling device, the method, or the use of embodiment18, wherein the ferrous material comprises a magnet.

[0218] 20. The ocular cooling device, the method, or the use of any one of embodiments 1-19, wherein the cold side and the hot side of the thermoelectric cooler are coupled by p-type and n-type semiconductor pillars.

[0219] 21. The ocular cooling device, the method, or the use of any one of embodiments 1-20, wherein the chamber is a heat exchanger.

[0220] 22. The ocular cooling device, the method, or the use of any one of embodiments 1-21 , wherein the chamber further comprises a fluid or a gas.

[0221] 23. The ocular cooling device, the method, or the use of embodiment22, wherein the inlet tube allows for inlet of a cold fluid or a cold gas into the chamber.

[0222] 24. The ocular cooling device, the method, or the use of embodiment22 or 23, wherein the outlet tube allows for outlet fluid or a gas from the chamber that is warmer than a fluid or a gas entering the chamber.

[0223] 25. The ocular cooling device, the method, or the use of any one of embodiments 1-24, wherein the one or more power supply lines supply power to the thermoelectric cooler.

[0224] 26. The ocular cooling device, the method, or the use of any one of embodiments 1-25, wherein at least a portion of an extraocular tissue of the subject’s eye positions over a flange of the contact ring.

[0225] 27. The ocular cooling device, the method, or the use of embodiment26, wherein the extraocular tissue is an eyelid.

[0226] 28. The ocular cooling device, the method, or the use of embodiment27, wherein at least a portion of the eyelid closes over the second side of the contact ring.

[0227] 29. The ocular cooling device, the method, or the use of any one of embodiments 1 to 28, wherein the contact ring comprises a radius of curvature of at least about 2.0 mm to at least about 15.0 mm.

[0228] 30. The ocular cooling device, the method, or the use of any one of embodiments 1-29, wherein one or more of the contact ring, the thermoelectric cooler, or the chamber comprises a central void.

[0229] 31 . The ocular cooling device, the method, or the use of embodiment30, wherein the central void comprises a diameter of at least about 5 mm to at least about 12 mm.

[0230] 32. The ocular cooling device, the method, or the use of embodiment30 or 31 , wherein the central void comprises a light penetrable window.

[0231] 33. The ocular cooling device, the method, or the use of embodiment32, wherein the light penetrable window is a transparent window or a translucent window.

[0232] 34. The ocular cooling device, the method, or the use of embodiment32 or 33, wherein the light penetrable window comprises a glass, an acrylic, a polycarbonate, or a transparent ceramic.

[0233] 35. The ocular cooling device, the method, or the use of any one of embodiments 1-34, wherein the second side of the contact ring comprises a material having a thermal conductivity level that is less than 0.5W / (m»K).

[0234] 36. An ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: (a) a first side that contacts the subject’s eye; and (b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m*K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye; and (ii) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

[0235] 37. An ocular cooling device, comprising: (i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: (a) a first side that contacts the subject’s eye; and (b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m*K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye; (ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; (iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube; and (iv) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

[0236] 38. The ocular cooling device, the method, or the use of any one of embodiments 30-36, wherein at least a portion of an anterior sclera, a cornea, a pupil, or a retina of the subject’s eye is visible through the central void.

[0237] 39. The ocular cooling device, the method, or the use of any one of embodiments 1-38, wherein the contact ring comprises a non-transparent or an opaque material.

[0238] 40. The ocular cooling device, the method, or the use of embodiment39, wherein the contact ring comprises a metal.

[0239] 41 . The ocular cooling device, the method, or the use of embodiment40, wherein the contact ring is comprised of a solid or homogeneous material.

[0240] 42. The ocular cooling device, the method, or the use of any one of embodiments 1-41 , wherein a contact area between the contact ring and the subject’s eye is anterior to a bulbus oculi equator of the subject’s eye.

[0241] 43. The ocular cooling device, the method, or the use of any one of embodiments 35 to 42, wherein the material having a thermal conductivity level that is less than 0.5W / (m*K) is a silicone.

[0242] 44. The ocular cooling device, the method, or the use of any one of embodiments 26-35, wherein the first side of the contact ring comprises a material having a thermal conductivity level that is at least 0.5W / (m*K).

[0243] 45. The ocular cooling device, the method, or the use of embodiment44, wherein the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a material selected from the group consisting of glass, ceramic, metal, acrylic, and glass-ceramic.

[0244] 46. The ocular cooling device, the method, or the use of embodiment44 or 45, wherein the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a thermally conductive additive.

[0245] 47. The ocular cooling device, the method, or the use of embodiment46, wherein the thermally conductive additive is selected from the group consisting of carbon nanotubes, graphite, and aluminum powder.

[0246] 48. The ocular cooling device, the method, or the use of any one of embodiments 26-47, wherein the first side of the contact ring decreases a heat level drawn from the portion of the extraocular tissue positioned over the flange of the contact ring, relative to a control.

[0247] 49. The ocular cooling device, the method, or the use of any one of embodiments 1-48, wherein the contact ring is an eye cooling ring.

[0248] 50. The ocular cooling device, the method, or the use of any one of embodiments 1-49, wherein the contact ring further comprises one or more sensors or one or more electrodes.

[0249] 51 . The ocular cooling device, the method, or the use of embodiment50, wherein the one or more sensors comprise a pressure sensor, a temperature sensor, or an optical sensor.

[0250] 52. The ocular cooling device, the method, or the use of embodiment51 , wherein the temperature sensor comprises a thermistor.

[0251] 53. The ocular cooling device, the method, or the use of embodiment51 , wherein the one or more electrodes sense one or more biopotentials from a surface of the subject’s eye.

[0252] 54. The ocular cooling device, the method, or the use of any one of embodiments 50-53, wherein the one or more sensors or the one or more electrodes contact at least a portion of the subject’s eye.

[0253] 55. The ocular cooling device, the method, or the use of any one of embodiments 50-54, wherein the one or more sensors or the one or more electrodes are used as an input to a control circuit or a computational model.

[0254] 56. The ocular cooling device, the method, or the use of any one of embodiments 1-55, further comprising a heat sink.

[0255] 57. The ocular cooling device of embodiment 56, wherein the chamber comprises the heat sink.

[0256] 58. The ocular cooling device, the method, or the use of embodiment57, wherein the heat sink is thermally coupled to the contact ring or to the hot side of the thermoelectric cooler.

[0257] 59. The ocular cooling device, the method, or the use of any one of embodiments 56-58, wherein the heat sink is a finned heat sink.

[0258] 60. The ocular cooling device, the method, or the use of any one of embodiments 1-59, wherein the inlet tube, the outlet tube, or the one or more power supply lines connect the ocular cooling device to a housing.

[0259] 61 . The ocular cooling device, the method, or the use of embodiment60, wherein the housing comprises one or more of a pump, a power supply, a heat dissipating component, or a rectifier.

[0260] 62. The ocular cooling device, the method, or the use of embodiment61 , wherein the housing is distally located to a limbus of the subject’s eye.

[0261] 63. The ocular cooling device, the method, or the use of embodiment61 , wherein the rectifier converts an alternating current (AC) to a direct current (DC).

[0262] 64. The ocular cooling device, the method, or the use of embodiment61 or 63, wherein the rectifier powers the pump or the thermoelectric cooler.

[0263] 65. The ocular cooling device, the method, or the use of embodiment61 , wherein the heat dissipating component comprises a chemical cold pack, an ice bath, or a heat pump.

[0264] 66. The ocular cooling device, the method, or the use of embodiment65, wherein the heat pump is a second thermoelectric cooler.

[0265] 67. The ocular cooling device, the method, or the use of any one of embodiments 61 to 66, wherein the pump comprises a fluid or a gas.

[0266] 68. The ocular cooling device, the method, or the use of embodiment67, wherein the fluid or the gas is transported by the inlet tube or the outlet tube of the ocular cooling device.

[0267] 69. The ocular cooling device, the method, or the use of any one of embodiments 60-63, wherein the housing is positioned to be worn by the subject.

[0268] 70. The ocular cooling device, the method, or the use of any one of embodiments 60-69, wherein the housing is a chest pack.

[0269] 71. The ocular cooling device, the method, or the use of any one of embodiments 1-70, wherein the ocular cooling device, the method, or the use reduces a temperature level in one or more of a retina, a vitreous, a posterior pole, or a proximal optic nerve of the subject’s eye.

[0270] 72. The ocular cooling device, the method, or the use of any one of embodiments 1-70, wherein the ocular cooling device, the method, or the use cools at least a portion of the subject’s eye to greater than about 5°C to less than 32°C.

[0271] 73. The ocular cooling device, the method, or the use of any one of embodiments 1-56, wherein the subject is a human subject.

Claims

CLAIMSI / We claim:1 . An ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

2. A method of reducing an eye temperature level in a subject in need thereof relative to a control, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce the eye temperature level in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

3. Use of an ocular cooling device for reducing an eye temperature level in a subject in need thereof relative to a control, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce the eye temperature level in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

4. A method of reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising:an inlet tube and an outlet tube.

5. Use of an ocular cooling device for reducing or preventing an ocular pain, an ocular inflammation, or an intraocular pressure in a subject in need thereof relative to a control, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

6. The method or the use of claim 4 or 5, wherein the method or the use reduces or prevents the ocular pain, the ocular inflammation, or the intraocular pressure during or after an ocular procedure.

7. The method or the use of claim 6, wherein the ocular procedure comprises an intraocular injection.

8. The method or the use of any one of claims 2-7, wherein the control comprises the subject at baseline.

9. A method of treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof, the method comprising, positioning an ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube.

10. Use of an ocular cooling device for treating or preventing a retinal ischemia, a retinal hypoxia, a vision loss, or an optic nerve injury in a subject in need thereof, comprising, positioning the ocular cooling device on the subject’s eye for a period of time effective to reduce an eye temperature in the subject, the ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover the subject’s eye, the contact ring comprising: a first side that contacts the subject’s eye and a second side opposite to the first side;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines; and(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising:an inlet tube and an outlet tube.

11. The method or the use of claim 9 or 10, wherein the optic nerve injury comprises a traumatic optic nerve injury.

12. The method or the use of claim 9 or 10, wherein the retinal ischemia is a retinal ischemia from central retinal artery occlusion (CRAO), non-arteritic ischemic optic neuropathy (NAION), retinal detachment, or ocular trauma.

13. The method or the use of any one of claims 2-12, wherein the method or the use is performed in vivo.

14. The ocular cooling device, the method, or the use of any one of claims 1 to 13, wherein the ocular cooling device is a portable ocular cooling device.

15. The ocular cooling device, the method, or the use of any one of claims 1 to 14, wherein the contact ring is coupled by p-type and n-type semiconductor pillars to the thermoelectric cooler.

16. The ocular cooling device, the method, or the use of any one of claims 1 to 15, wherein the thermoelectric cooler is coupled to the chamber.

17. The ocular cooling device, the method, or the use of claim 15 or 16 wherein the thermoelectric cooler is coupled to the contact ring or to the chamber with a thermally conductive adhesive, a locking mechanism, or a magnetic force.

18. The ocular cooling device, the method, or the use of claim 17, wherein the magnetic force comprises a ferrous material.

19. The ocular cooling device, the method, or the use of claim 18, wherein the ferrous material comprises a magnet.

20. The ocular cooling device, the method, or the use of any one of claims 1-19, wherein the cold side and the hot side of the thermoelectric cooler are coupled by p-type and n-type semiconductor pillars.21 . The ocular cooling device, the method, or the use of any one of claims 1-20, wherein the chamber is a heat exchanger.

22. The ocular cooling device, the method, or the use of any one of claims 1-21 , wherein the chamber further comprises a fluid or a gas.

23. The ocular cooling device, the method, or the use of claim 22, wherein the inlet tube allows for inlet of a cold fluid or a cold gas into the chamber.

24. The ocular cooling device, the method, or the use of claim 22 or 23, wherein the outlet tube allows for outlet fluid or a gas from the chamber that is warmer than a fluid or a gas entering the chamber.

25. The ocular cooling device, the method, or the use of any one of claims 1-24, wherein the one or more power supply lines supply power to the thermoelectric cooler.

26. The ocular cooling device, the method, or the use of any one of claims 1-25, wherein at least a portion of an extraocular tissue of the subject’s eye positions over a flange of the contact ring.

27. The ocular cooling device, the method, or the use of claim 26, wherein the extraocular tissue is an eyelid.

28. The ocular cooling device, the method, or the use of claim 27, wherein at least a portion of the eyelid closes over the second side of the contact ring.

29. The ocular cooling device, the method, or the use of any one of claims 1 to 28, wherein the contact ring comprises a radius of curvature of at least about 2.0 mm to at least about 15.0 mm.

30. The ocular cooling device, the method, or the use of any one of claims 1- 29, wherein one or more of the contact ring, the thermoelectric cooler, or the chamber comprises a central void.31 . The ocular cooling device, the method, or the use of claim 30, wherein the central void comprises a diameter of at least about 5 mm to at least about 12 mm.

32. The ocular cooling device, the method, or the use of claim 30 or 31 , wherein the central void comprises a light penetrable window.

33. The ocular cooling device, the method, or the use of claim 32, wherein the light penetrable window is a transparent window or a translucent window.

34. The ocular cooling device, the method, or the use of claim 32 or 33, wherein the light penetrable window comprises a glass, an acrylic, a polycarbonate, or a transparent ceramic.

35. The ocular cooling device, the method, or the use of any one of claims 1- 34, wherein the second side of the contact ring comprises a material having a thermal conductivity level that is less than 0.5W / (m»K).

36. An ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising:(a) a first side that contacts the subject’s eye; and(b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m*K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye; and(ii) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

37. An ocular cooling device, comprising:(i) a contact ring sized and shaped to partially cover a subject’s eye, the contact ring comprising:(a) a first side that contacts the subject’s eye; and(b) a second side opposite to the first side comprising a material having a thermal conductivity level that is less than 0.5W / (m«K) and a flange that positions under at least a portion of an extraocular tissue of the subject’s eye;(ii) a thermoelectric cooler comprising: a cold side coupled to the second side of the contact ring, a hot side opposite to the cold side, and one or more power supply lines;(iii) a chamber coupled to the hot side of the thermoelectric cooler, the chamber comprising: an inlet tube and an outlet tube; and(iv) a central void having a diameter of at least about 10mm to at least about 12 mm and comprising a light penetrable window.

38. The ocular cooling device, the method, or the use of any one of claims SO- 36, wherein at least a portion of an anterior sclera, a cornea, a pupil, or a retina of the subject’s eye is visible through the central void.

39. The ocular cooling device, the method, or the use of any one of claims 1- 38, wherein the contact ring comprises a non-transparent or an opaque material.

40. The ocular cooling device, the method, or the use of claim 39, wherein the contact ring comprises a metal.41 . The ocular cooling device, the method, or the use of claim 40, wherein the contact ring is comprised of a solid or homogeneous material.

42. The ocular cooling device, the method, or the use of any one of claims 1- 41 , wherein a contact area between the contact ring and the subject’s eye is anterior to a bulbus oculi equator of the subject’s eye.

43. The ocular cooling device, the method, or the use of any one of claims 35 to 42, wherein the material having a thermal conductivity level that is less than 0.5W / (m»K) is a silicone.

44. The ocular cooling device, the method, or the use of any one of claims 26- 35, wherein the first side of the contact ring comprises a material having a thermal conductivity level that is at least 0.5W / (m»K).

45. The ocular cooling device, the method, or the use of claim 44, wherein the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a material selected from the group consisting of glass, ceramic, metal, acrylic, and glassceramic.

46. The ocular cooling device, the method, or the use of claim 44 or 45, wherein the material having a thermal conductivity level that is at least 0.5W / (m*K) comprises a thermally conductive additive.

47. The ocular cooling device, the method, or the use of claim 46, wherein the thermally conductive additive is selected from the group consisting of carbon nanotubes, graphite, and aluminum powder.

48. The ocular cooling device, the method, or the use of any one of claims 26-47, wherein the first side of the contact ring decreases a heat level drawn from the portion of the extraocular tissue positioned over the flange of the contact ring, relative to a control.

49. The ocular cooling device, the method, or the use of any one of claims 1-48, wherein the contact ring is an eye cooling ring.

50. The ocular cooling device, the method, or the use of any one of claims 1- 49, wherein the contact ring further comprises one or more sensors or one or more electrodes.51 . The ocular cooling device, the method, or the use of claim 50, wherein the one or more sensors comprise a pressure sensor, a temperature sensor, or an optical sensor.

52. The ocular cooling device, the method, or the use of claim 51 , wherein the temperature sensor comprises a thermistor.

53. The ocular cooling device, the method, or the use of claim 51 , wherein the one or more electrodes sense one or more biopotentials from a surface of the subject’s eye.

54. The ocular cooling device, the method, or the use of any one of claims SO-53, wherein the one or more sensors or the one or more electrodes contact at least a portion of the subject’s eye.

55. The ocular cooling device, the method, or the use of any one of claims SO-54, wherein the one or more sensors or the one or more electrodes are used as an input to a control circuit or a computational model.

56. The ocular cooling device, the method, or the use of any one of claims 1-55, further comprising a heat sink.

57. The ocular cooling device of claim 56, wherein the chamber comprises the heat sink.

58. The ocular cooling device, the method, or the use of claim 57, wherein the heat sink is thermally coupled to the contact ring or to the hot side of the thermoelectric cooler.

59. The ocular cooling device, the method, or the use of any one of claims 56-58, wherein the heat sink is a finned heat sink.

60. The ocular cooling device, the method, or the use of any one of claims 1-59, wherein the inlet tube, the outlet tube, or the one or more power supply lines connect the ocular cooling device to a housing.61 . The ocular cooling device, the method, or the use of claim 60, wherein the housing comprises one or more of a pump, a power supply, a heat dissipating component, or a rectifier.

62. The ocular cooling device, the method, or the use of claim 61 , wherein the housing is distally located to a limbus of the subject’s eye.

63. The ocular cooling device, the method, or the use of claim 61 , wherein the rectifier converts an alternating current (AC) to a direct current (DC).

64. The ocular cooling device, the method, or the use of claim 61 or 63, wherein the rectifier powers the pump or the thermoelectric cooler.

65. The ocular cooling device, the method, or the use of claim 61 , wherein the heat dissipating component comprises a chemical cold pack, an ice bath, or a heat pump.

66. The ocular cooling device, the method, or the use of claim 65, wherein the heat pump is a second thermoelectric cooler.

67. The ocular cooling device, the method, or the use of any one of claims 61 to 66, wherein the pump comprises a fluid or a gas.

68. The ocular cooling device, the method, or the use of claim 67, wherein the fluid or the gas is transported by the inlet tube or the outlet tube of the ocular cooling device.-SO-69. The ocular cooling device, the method, or the use of any one of claims 60- 63, wherein the housing is positioned to be worn by the subject.

70. The ocular cooling device, the method, or the use of any one of claims 60-69, wherein the housing is a chest pack.71 . The ocular cooling device, the method, or the use of any one of claims 1-70, wherein the ocular cooling device, the method, or the use reduces a temperature level in one or more of a retina, a vitreous, a posterior pole, or a proximal optic nerve of the subject’s eye.

72. The ocular cooling device, the method, or the use of any one of claims 1- 70, wherein the ocular cooling device, the method, or the use cools at least a portion of the subject’s eye to greater than about 5°C to less than 32°C.

73. The ocular cooling device, the method, or the use of any one of claims 1- 56, wherein the subject is a human subject.

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