Mobile robotic intraocular drug delivery system

Abstract

The drug delivery device includes a drug delivery assembly configured to receive a portion of the patient's head and mounted on a helmet or support. The drug delivery assembly includes one or more imaging devices configured so that the patient's eye is within its field of view, an infusion assembly configured to receive the drug to be injected, and a staging assembly including one or more actuators configured to position the infusion assembly relative to the patient's eye. The controller receives one or more images from the one or more imaging devices, detects the position of the limbus of the patient's eye in the one or more images, and activates one or more actuators to drive a needle into the implantation position in the patient's eye and dispense the drug into the eye through the needle.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the priority and benefit of U.S. Provisional Patent Application No. 63 / 505,496, filed on June 1, 2023, which is hereby assigned to the assignee of this application and is incorporated herein by reference in its entirety as if fully set forth below and for all applicable purposes.

[0002] Introduction The present disclosure generally relates to an instrument used to provide intravitreal injection.

[0003] The light received by the eye is focused by the cornea and lens of the eye onto the retina located behind the eye, which contains photoreceptor cells. Between the lens and the retina inside the eye, there is a transparent gel known as the vitreous humor. Many diseases of the retina are treated by intravitreal injection, in which a drug is injected into the vitreous humor. Such diseases include age - related macular degeneration, retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and others. Once a disease requiring intravitreal injection is diagnosed, the patient may need to continue to receive injections regularly.

Summary of the Invention

Problems to be Solved by the Invention

[0004] In the art, it would be an advancement to facilitate the performance of intravitreal injection.

Means for Solving the Problems

[0005] In certain embodiments, the drug delivery device includes a drug delivery assembly configured to receive a portion of the patient's head. The drug delivery assembly includes one or more imaging devices configured to bring one of the patient's eyes into its field of view, and an infusion assembly configured to receive a drug to be injected into the patient's eye. The drug delivery assembly further includes a staging assembly, which includes one or more actuators configured to position the infusion assembly relative to the patient's eye. A controller is coupled to one or more imaging devices and the staging assembly and configured to receive one or more images from one or more imaging devices. The controller is configured to detect the position of the limbus of the patient's eye in one or more images. The controller is configured to actuate one or more actuators so that, depending on the position of the limbus, a needle attached to the infusion assembly is driven into the implantation position in the patient's eye, and the drug is dispensed into the eye through the needle.

[0006] In a particular embodiment, a drug delivery method includes positioning a portion of the patient's head within a drug delivery assembly comprising one or more imaging devices configured to place one of the patient's eyes within its field of view, an injection assembly configured to receive a drug to be injected into the patient's eye, and a staging assembly comprising one or more actuators configured to position the injection assembly relative to the patient's eye; receiving one or more images from one or more imaging devices by a controller; detecting the position of the limbus of the patient's eye in one or more images by the controller; and acting on one or more actuators by the controller so that a needle attached to the injection assembly is driven into the implantation position in the patient's eye according to the position of the limbus.

[0007] To enable a more detailed understanding of the features of this disclosure described above, a more specific description of this disclosure, briefly outlined above, can be obtained by referring to embodiments, some of which are shown in the accompanying drawings. However, it should be noted that the accompanying drawings show only exemplary embodiments and are therefore not intended to limit the scope of the invention, and other equally effective embodiments may be realized. [Brief explanation of the drawing]

[0008] [Figure 1A-1B] Figure 1A is a side view of a mobile robotic intravitreal drug delivery device according to a specific embodiment. Figure 1B is a top view of the device shown in Figure 1A. [Figure 2A] Figure 2A is a side view of an alternative embodiment of a mobile robotic intravitreal drug delivery device according to a specific embodiment. [Figure 2B] Figure 2B is a top view of the apparatus shown in Figure 2A. [Figure 3] Figure 3 is a schematic diagram of the components for implementing a robotic intravitreal drug delivery device according to a specific embodiment. [Figure 4A-4B] Figures 4A to 4B show actuators for injection assemblies according to a specific embodiment. [Figures 5A-5D] Figures 5A to 5D show exemplary injection assemblies according to a specific embodiment. [Figure 6] Figure 6 is a schematic block diagram of the electronic components of a mobile robotic intravitreal drug delivery device according to a specific embodiment. [Figure 7] Figure 7 is a process flow diagram of a method for preparing drug delivery using a mobile robotic intravitreous drug delivery device according to a specific embodiment. [Figure 8] Figure 8 is a process flow diagram of a method for performing intravitreal injection using a mobile robotic intravitreal drug delivery device according to a specific embodiment. [Modes for carrying out the invention]

[0009] For ease of understanding, the same reference numerals are used to indicate the same elements common to multiple drawings whenever possible. Elements and features of one embodiment are considered to be advantageously incorporated into other embodiments without further specification.

[0010] Figure 1A shows an exemplary mobile robotic intravitreal drug delivery device 100 (hereinafter referred to as "drug delivery device 100"). The drug delivery device 100 includes a drug delivery assembly 102 connected to a chin rest 104. The drug delivery assembly 102 receives a portion of the patient's head 106, with the patient's chin resting on the chin rest 104. The drug delivery assembly 102 may include some or all of the following: a forehead support, a cheek support, a temporal support, or supports for engaging with other portions of the patient's head 106. The drug delivery assembly 102 may include structures for fixing or otherwise holding the patient's head 106, such as clamps for pressing pads against the temporal region of the patient's head 106, a headband that wraps around the patient's head 106 and is fixed to the drug delivery assembly 102, or other structures. Alternatively, the patient may press their head against the drug delivery assembly 102 and chin rest 104 to ensure sufficient stability for performing an intravitreal injection as described later. The drug delivery assembly 102 is positioned around the patient's eye 108, covering it.

[0011] The drug delivery assembly 102 may be housed separately from the controller 110 to reduce its weight, and may be connected to the controller 110 by a cable 112 or by a wireless connection. The controller 110 includes logic (e.g., a computing device) for controlling the actuators and other components of the drug delivery assembly 102. The controller 110 may include a power source such as a rechargeable battery or an adapter for connecting to a power outlet.

[0012] The drug delivery assembly 102 and chin rest 104 may be mounted on a support 114. The support 114 may be configured to rest on a floor, tabletop, or other stable support surface, and the drug delivery assembly 102 and chin rest 104 may be positioned longitudinally to support the head 106 of a patient seated near the support 114. The support 114 may be implemented as a tripod, as shown in the figure, which may be foldable for easy portability. The support 114, such as the tripod shown in the figure, may have built-in or detachable weights, stabilizing legs, or other functional parts for stability during use. The support 114 may be longitudinally adjustable to facilitate positioning the drug delivery assembly 102 and chin rest 104 at a comfortable height for the patient. The chin rest 104 may be similarly adjustable.

[0013] Referring to Figures 2A and 2B, in an alternative implementation, the drug delivery assembly 102 is mounted on a helmet 200, which is fitted to the patient's head 106 so as to cover the eyes 108. The controller 110 may be mounted inside the helmet 200 or housed separately, as in the embodiments of Figures 1A and 1B, and connected by a cable 112. The helmet 200 may include a headband 202 and a tension adjuster 204. The patient or other operator may use the tension adjuster 204 to pull the headband 202, holding the patient's head 106 snugly inside the helmet 200, so that the forehead of the patient's head 106 is pressed against the drug delivery assembly 102, making it difficult for the patient's head 106 to move relative to the helmet 200 during drug delivery. The helmet 200 may offer the advantage of preventing too much light from reaching the patient's eyes 108, thereby making the needle of the drug delivery assembly 102 difficult to see and reducing the likelihood of the patient flinching or otherwise moving their body in fear.

[0014] While the embodiments in Figures 1A, 1B, 2A, and 2B show the patient's head 106 in a seated or standing position, other embodiments may also be used when the patient is in a reclined position, such as leaning backward and looking upward.

[0015] Referring to Figure 3, the drug delivery assembly 102 includes a frame 300. The frame 300 may be implemented as a track or rail, and components may be fixed along it at various positions. The frame 300 may include one or more mounting structures 302 attached thereto. The mounting structures 302 include one or more alignment functions 304 that allow for rigid and repeated mounting to the mounting structures 302. The mounting structures 302 may have one or more degrees of adjustment, including some or all of the following: (a) being fixable to the frame 300 within a conceivable range of positions; (b) a translation adjustment mechanism 306 allowing each mounting structure 302 to be translatedly adjusted relative to its attachment point to the frame 300; and (c) a rotation adjustment mechanism 308 allowing the mounting structure 302 to be rotationally adjusted relative to its attachment point to the frame 300. One or more locking mechanisms 310 may be used to lock the mounting structure 302 against the frame 300, preventing further adjustment along the frame 300 or the use of the translational adjustment mechanism 306 and rotational adjustment mechanism 308. In some uses, the drug delivery assembly 102 may be set up for individual patients and taken home by the patients. Therefore, the mounting structure 302 may be set up by a professional operator and then locked in place using the locking mechanism 310 to prevent further adjustment. The translational adjustment mechanism 306 and rotational adjustment mechanism 308 may facilitate manual adjustment by a professional operator or may include an electronic actuator or an interface controlled by an electronic actuator. In other embodiments, the patient may adjust the position of the mounting structure 302 so that the position of the patient's head 106 and eye 108 is aligned with the needle attached to the mounting structure 302, as described later. For example, the controller 110 may provide guidance in the form of verbal or visual instructions based on the output of one or more cameras, e.g., one or more cameras 318 described later, that place the patient's eye 108 in its field of view. The customer may adjust the mounting structure manually or by controlling one or both of the translational and rotational adjustment mechanisms 306, 308 according to the guidance.

[0016] In some embodiments, the staging assembly 312 can be fixed to each mounting structure 302. Thus, the same staging assembly 312 can be used for treating both eyes 108 of a patient. The staging assembly 312 engages with the alignment function 304 of the mounting structure 302 to rigidly hold the staging assembly 312 relative to the mounting structure 302, ensuring precise positioning of the staging assembly 312 relative to the mounting structure 302 (e.g., within 0.01 millimeters or 1 micrometer). The staging assembly 312 can be fixed to each structure using a latch 314 that can be attached and detached by the patient without the use of tools.

[0017] In some applications, the patient does not need to remove their head 106 from the drug delivery assembly 102 in between treatments of both of their eyes 108. Therefore, there may be two staging assemblies 312, or the staging assembly 312 may be automatically moved from one mounting structure 302 to the other, and may be slid on or along a track formed thereon, for example, by manual or mechanical operation.

[0018] The staging assembly 312 includes one or more actuators that control the position of the injection assembly 316 attached to the staging assembly 312. The staging assembly 312 attempts to compensate for variations in the positioning of the patient's head 106 relative to the frame 300, misalignment of the patient's eyes 108, or other possible causes of variations in the positioning of the patient's head 106 and eyes 108 when the mounting structure 302 is set. In some embodiments, the controller 110 performs an alignment check to facilitate alignment of the patient's eyes 108 with the staging assembly 312. For example, using eye tracking from an image from the camera 318, the controller 110 can detect the degree of misalignment, particularly misalignment outside the range of motion of the staging assembly 312, and provide feedback to the patient to correct the misalignment. The feedback can be in the form of an indication displayed on a screen, such as a screen implementing a fixation target 324. For example, a box and a target corresponding to the current position of the patient's eyes 108 can be shown to the patient. The patient can be instructed to move their head 106 relative to the drug delivery assembly 102 while the controller updates the position of the target based on the current position of the patient's eyes 108 so that the target enters the box. Then, the patient can fix their head 106 relative to the drug delivery assembly 102.

[0019] The amount of variation can be small, whereby the range of motion of the staging assembly 312 can also be similarly small, for example, less than 1 centimeter, less than 5 millimeters, or less than 2 millimeters along one or more translational directions, or less than 10 degrees, less than 5 degrees, or less than 2 degrees in one or more rotational directions.

[0020] The adjustment of the staging assembly 312 can be performed using feedback from one or more sensors such as one or more cameras 318. For example, one or more cameras 318 can be attached to the frame 300 and oriented to image the patient's left eye 108, and one or more cameras 318 can be attached to the frame 300 and oriented to image the patient's right eye 108. Alternatively, a set of one or more cameras 318 may be repositioned to image the right or left eye 108. For example, one or more cameras 318 can be attached to the staging assembly 312. When two or more cameras 318 image the individual eyes 108, multiple images can be used to identify features in three dimensions.

[0021] The camera 318 can be a color or infrared camera. The camera 318 is merely an example of an imaging device that can be used. Other imaging devices and images obtained from such imaging devices may be used instead of the camera 318 and the images received from the camera 318. For example, other imaging devices can include optical coherence tomography (OCT) devices, scanning laser ophthalmoscopes (SLOs), or other types of imaging devices. OCT devices are particularly useful for tracking the position of needles during insertion, injection, and removal.

[0022] The controller 110 receives images from one or more cameras 318 and can detect features such as the tip of the needle of the injection assembly 316 and other recognizable features of the injection assembly 316, as well as one or more anatomical sites such as the limbus 320 of the patient's eye 108. Other identifiable anatomical sites may include the lens and retina. The controller 110 can then control the actuators of the staging assembly 312 so that the needle of the injection assembly 316 is inserted into the patient's eye 108 at a predetermined distance from the limbus 320 and in a predetermined orientation, for example, 3 to 3.5 millimeters in aphakia / pseudophakia eyes and 3.5 to 4 millimeters in crystalline eyes. In some embodiments, the controller 110 generates a three-dimensional model of the eye 108 and uses this model to accurately guide the needle so as not to damage eye tissue such as the lens, retina, or other anatomical sites.

[0023] One or more other sensors, such as an intraocular pressure (IOP) sensor 322, may be incorporated into the drug delivery assembly 102. The IOP sensor 322 may be a contact or non-contact sensor and may be used to ensure that the IOP of the patient's eye 108 does not rise to an unsafe level during intravitreal injection. There may be a separate IOP sensor 322 for each eye, or a single IOP sensor 322 may be mounted at different positions on the frame 300 or on the staging assembly 312 to measure the IOP of each eye 108.

[0024] The drug delivery assembly 102 may include one or more fixation targets 324. The fixation targets 324 may be embodied as a still image, a light source, a screen for displaying the fixation targets, or other devices. A separate fixation target 324 may be provided for each eye 108, or a single fixation target may be moved between positions for the left eye 108 and the right eye 108, for example, by being mounted on a staging assembly 312. In some embodiments, one fixation target 324 is centrally positioned for use by both eyes 108, i.e., the patient can orient each eye 108 toward their nose to expose the sclera for injection. Alternatively, a single screen implementing the fixation targets 324 may display the fixation targets in different positions for each eye 108. The position of the fixation targets may be adjusted using software run by a controller 110 or remote observer to guide the patient to position the eye 108 at a desired angle.

[0025] With respect to Figures 4A and 4B, it should be understood that the staging assembly 312 may be schematically represented as shown in the figures, and that relative dimensions may differ from those shown. The staging assembly 312 may include a base 400 that is fixed to a mounting structure 302 and configured to be secured in place by a latch 314. One or more linear actuators 402, 404, 406 may be mounted thereon. For example, linear actuator 402 induces movement in the X direction, linear actuator 404 induces movement in the Y direction, and linear actuator 406 induces movement in the Z direction, and the X, Y, and Z directions are substantially perpendicular to each other (e.g., within 3 degrees). In the embodiment shown in the figures, linear actuator 402 is mounted to the base 400, linear actuator 404 is mounted to linear actuator 402 and moved in the X direction by linear actuator 402, linear actuator 406 is mounted to linear actuator 404 and moved in the Y direction by linear actuator 404, and injection assembly 316 is mounted to linear actuator 406. The linear actuator 406 may induce movement of the injection assembly 316 toward and toward the patient's eye 108, including, until the needle of the injection assembly 316 is driven into the patient's eye 108. The ranges of motion of the linear actuators 402, 404, and 406 do not have to be equal. For example, the degree of displacement in the X and Y directions may be relatively small compared to the movement along the Z direction required to move the needle of the injection assembly 316 toward the vicinity of the eye 108 and, optionally, to a predetermined depth within the eye 108.

[0026] The linear actuators 402, 404, and 406 in the figure are illustrative only. The arrangement, i.e., stacking, of the linear actuators 402, 404, and 406 may be in a different order than that shown. One or both of actuators 402 and 404 may be embodied as rotary actuators having rotation axes parallel to the X and Y directions, respectively. One or both of the linear actuators 402 and 404 may be embodied as arc-shaped actuators with axes parallel to the X and Y directions, respectively, and having a remote motion center, for example, located on or offset from the surface of the patient's eye 108.

[0027] As shown in Figures 5A-5C, the injection assembly 316 may have some or all of the attributes and / or functions described below. The injection assembly 316 may include a tray 500 defining one or more recesses 502 for receiving syringes, for example, three recesses 502 for receiving syringes containing anesthetics, disinfectants, and drugs delivered by intravitreal injection. For example, each recess 502 may include a groove 502a for receiving the flange of the syringe and a recess 502b connected to the groove 502a for receiving the barrel of the syringe.

[0028] The plunger actuator 504 is positioned to push down the plunger 510 of a syringe 508 located within the recess 502. In some embodiments, one plunger actuator 504 is used and moved by a positioning actuator 506 between the position shown in the figure and two other positions 504a, 504b to push down the plunger 510 of the syringes located in each of the recesses 502. In other embodiments, separate plunger actuators 504 are provided to push down the plunger 510 of the syringes 508 located within each recess 502.

[0029] The syringe 508 can be held in the recess 502 by a lid 512 or other retaining structure. The lid 512 can be coupled to a lid actuator 514, which can move to the open position shown in Figures 5A and 5B, and to the closed position shown in Figure 5C, where the lid 512 is positioned over the syringe 508 positioned in the recess 502. The lid 512 may be flat, or it may include recesses to receive part of the syringe 508 when the lid 512 is in the closed position covering the tray 500. For example, the lid 512 may include recesses 502, similar to the tray 500, where each recess 502 includes a groove 502a for receiving the flange of the syringe 508 and a recess 502b for receiving the barrel of the syringe 508.

[0030] Figure 5D shows an alternative implementation of the injection assembly 316. In the embodiment shown in the figure, the injection assembly 316 includes one or more storage units 520, for example, storage units 520 for containing drugs to be administered, anesthetics, and disinfectants. The storage units 520 may be separate components or may be joined to one another by fasteners, placement in a common housing, or simultaneous molding. Each storage unit 520 may have an outlet for discharging a fluid formed therein, for example, in the form of a subcutaneous needle 522 or a nozzle 524.

[0031] Each storage unit 520 may have an associated pump 526. The pump 526 of each storage unit 520 can be used to push fluid out of the outlet of the storage unit 520. The pump 526 may be replaced with another propulsion source. For example, pressurized fluid may be pushed into the storage unit 520 and engage with a piston or bladder to push the fluid out of the storage unit 520.

[0032] Each storage unit 520 may have an inlet 528 for filling the storage unit 520. The inlet 528 may be connected to a vial 530 or syringe containing the fluid to be filled into the storage unit 520. The fluid may be pushed into the storage unit 520 using the syringe or other pressure source. Alternatively, the fluid may be drawn from the vial 530 through the inlet 528 of the storage unit 520 by operating the pump 526 of the storage unit 520. In other implementations, the fluid may be drawn through the inlet 528 or outlet of the storage unit 520 to a bladder within the storage unit 520 by depressurizing the area around the bladder within the storage unit 520, for example, through a port connected to a pneumatic source. In some embodiments, the storage unit 520 may be large enough to store multiple doses. In such embodiments, the infusion assembly 316 may include a cooling function to prevent degradation of the drug being infused.

[0033] The inlet 528 may include a one-way valve, a self-sealing polymer defining a hole for receiving a needle, a removable cap, or other opening and closing mechanism. In some embodiments, the injection assembly 316 is a disposable cartridge pre-filled with fluid, in which case the inlet 528 is omitted. For example, the storage section 520 may be filled from its outlet during manufacturing.

[0034] The injection assembly 316 according to the embodiments in Figures 5A-5C and 5D may be connected to the controller 110 and a power supply for supplying power to the actuators 504, 506, 514 or the pump 526 by any other connection, such as contacts on the injection assembly that engage with corresponding contacts on the staging assembly 312, a socket into which a connector coupled to the controller 10 is inserted, or any other connection.

[0035] Referring to Figure 6, the controller 110 is coupled to some or all of the one or more pumps 526, one or more cameras 318, one or more IOP sensors 322, and one or more fixation targets 324 by wired or wireless connections, optical fibers, or other types of connections. The controller 110 is configured to operate and deactivate the one or more pumps 526, one or more cameras 318, one or more IOP sensors 322, and one or more fixation targets 324. The controller 110 is configured to receive images from one or more cameras 318 and IOP readings from the IOP sensors 322. The controller 110 may receive feedback from the one or more pumps 526, such as measured pressure at the input and / or output of each of the one or more pumps 526, current drawn by each of the one or more pumps 526, or other information. In some embodiments, the feedback from one or more pumps 526 may be used to obtain estimated IOP readings, and one or more IOP sensors 322 may be omitted.

[0036] The controller 110 is coupled to one or more other components, such as an actuator 600 including some or all of the actuators 402, 404, 406, 504, 506, and 514 described herein, to control the operation of the actuator 600 and may receive feedback on the state of some or all of the actuator 600 (e.g., current angle or translational position, velocity, and / or acceleration). The staging assembly 312, mounting structure 302, and injection assembly 316 are detachable from each other and may include electrical contacts for transmitting power and control signals from the controller 110 to the actuators 504, 506, or pump 526 of the injection assembly 316.

[0037] The controller 110 may be coupled to one or more interlock sensors 602 that detect the status of the drug delivery device 100 with respect to the patient's head 106. For example, the interlock sensors 602 may detect whether the patient's chin is in contact with the chin rest, whether the patient's forehead is in contact with the forehead support, whether the staging assembly 312 is properly attached to one of the mounting structures 302, whether the injection assembly 316 is properly attached to the staging assembly 312, or whether any of the components described herein are properly positioned and functioning.

[0038] The controller 110 may be coupled to the wireless transceiver 604. The drug delivery device 100 is designed and can be used by patients in their homes, but physician supervision and management may still be provided remotely. Therefore, the operation of the controller 110 may be subject to authorizations and instructions received from the computing device 606 on the network 608 by the wireless transceiver 604. The controller 110 may authenticate a remote observer using the computing device 606 and then authorize control using the computing device 606. The remote observer may additionally interact with the patient during the procedure through output devices such as a screen, speaker, or other devices incorporated into the drug delivery device 102. Instructions to the patient may be output from the output devices automatically or in response to instructions from the remote observer. The patient may interact with the remote observer using input devices incorporated into the drug delivery device 102, such as one or more cameras 318, microphones, touchscreens, pointing devices, keyboards, or other input devices.

[0039] Figure 7 is a process flow diagram of method 700 for preparing drug delivery using drug delivery device 100. Method 700 includes, in step 702, filling an infusion assembly 316 with a fluid containing the drug to be delivered, an anesthetic, and a disinfectant, as described above with respect to Figures 5A-5D. Alternatively, a disposable infusion assembly 316 that is already filled with fluid may be provided, thereby eliminating the need for the patient to perform step 702.

[0040] Method 700 includes locking the injection assembly 312 in place on the staging assembly 312 in step 704. Before or after locking the injection assembly 312 in place on the staging assembly 312, in step 704, the staging assembly 312 may also be locked in place on one of the mounting structures 302. However, if two staging assemblies 312 are used, or if the staging assembly 312 is already locked in place on the correct mounting structure 302, step 704 of locking the staging assembly 312 in place may be omitted.

[0041] In some embodiments, the patient may, in step 706, set a retractor on the eye 108 to move the eyelid out of the way. In other embodiments, the patient holds the eyelid out of the way themselves, and no retractor is used. In yet another embodiment, a mechanically operated retractor is incorporated into the staging assembly 312 to automatically retract the eyelid.

[0042] Method 700 includes, in step 708, positioning the patient's head 106 within the drug delivery device 100. Step 708 may include placing the patient's chin on the chin rest 104, placing the patient's forehead and eyes within the drug delivery assembly 102, and optionally engaging a headband or clamp to restrict the movement of the patient's head 106 relative to the drug delivery assembly 102. Step 708 may also include placing the patient's head 106 within the helmet 200 and optionally tightening the headband 202 using a tension adjuster 204.

[0043] Method 700 may include administering an anesthetic and an antiseptic in step 710. Step 710 may be an automated step in which the anesthetic and antiseptic are dispensed by pushing the plunger of a syringe using a plunger actuator 504 or by operating a pump 526. The outlet of the syringe 508 or storage unit 520 used to dispense the anesthetic and antiseptic may be positioned close to the eye 108 being treated, for example, within 1 millimeter, or in contact with the eye 108. Alternatively, the fluid may be sprayed in step 710, thereby eliminating the need for such close proximity. In some embodiments, step 710 is performed manually by the patient before step 708 is performed.

[0044] Figure 8 is a process flow diagram of method 800 for performing intravitreal injection using a drug delivery device 100. Method 800 may be performed after the execution of method 700 by the controller 110 activating the components of the drug delivery device 100. Method 800 may also be performed after waiting for a predetermined time after step 710 of method 700 for the anesthetic and disinfectant to take effect.

[0045] Method 800 includes activating the fixation target 324 in step 802. Activating the fixation target 324 may include activating light, such as a light-emitting diode, displaying an image on a screen, or otherwise providing a visual indicator visible to the eye being treated. If the fixation target is a stationary visible structure, step 802 may be omitted. Step 802 may include providing the patient with visual or auditory instructions to gaze at the fixation target 324.

[0046] Method 800 includes, in step 804, receiving one or more images from one or more cameras 318 in which the eye 108 to be treated is within its field of view. The images received in step 804 may be received in the form of one or more video feeds from one or more cameras 318.

[0047] Method 800 includes, in step 806, locating the corneal margin 320 represented in one or more images. Step 806 may be performed by aligning one or more labeled reference images to one or more images, the labeled reference images including labels for the corneal margin 320. Step 806 may be performed using a machine learning model, machine vision algorithm, or other technique trained to perform the task.

[0048] Method 800 may include in step 808 selecting an insertion point relative to the limbus 320, for example, any point within an acceptable offset range from the limbus 320, such as 3 to 3.5 millimeters in aphakia-positive eyes and 3.5 to 4 millimeters in phakic eyes. The angular position of the insertion point around the optical axis of the eye 108 to be treated may be selected as a position not obstructed by the patient's eyelid.

[0049] Method 800 may include, in step 810, acting the staging assembly 312 so that the needle of the injection assembly 316 is directed toward the insertion point along the operating direction of the actuator 406. In some embodiments, only translational positioning is performed. However, in other embodiments, step 810 may include changing the orientation of the injection assembly 316 so that the needle of the injection assembly 316 is directed at a desired angle with respect to the normal vector of the selected insertion point. The desired angle is as known in the art of intravitreal injection and may be chosen so that the needle does not come into contact with the lens and retina while positioning the drug near the retina or area of ​​the retina being treated when inserting the needle. Note that in some applications, the needle is relatively short (e.g., about 8 mm) and the angle and depth are not critical in preventing damage to ocular tissue. In other applications, the needle is used to provide subretinal injection, in which case the angle and depth of insertion become critical. In some embodiments, if the range of motion of the staging assembly 312 is insufficient to position the needle directed to the selected insertion point, method 800 may be terminated, or the user may be instructed on how to adjust the patient's head 106 relative to the drug delivery assembly 102 to enable proper positioning.

[0050] Step 810 may be performed after one or more further repetitions of some or all of steps 804, 806, and 808 to take into account the movement of the eye 108 being treated. Similarly, step 810 may include identifying a representation of the needle in one or more images received from one or more cameras 318 and using that representation as feedback to guide the positioning of the needle relative to the selected insertion site.

[0051] Method 800 may include, in step 812, transmitting real-time data to a remote observer, such as a computing device 606 of an authorized medical professional. The real-time data may include images from one or more cameras 318, for example, by transmitting a video feed from one or more cameras 318. The real-time data may include a representation of the selected insertion point from step 808 and the position and orientation of the needle, for example, in the form of annotations on the images from one or more cameras 318. The real-time data may include a report that the application of anesthetics and disinfectants was successful, for example, by including the respective application amounts. The real-time data may include the output of one or more interlock sensors 602, which indicate whether the patient is positioned correctly and whether the components of the drug delivery device are locked in place and functioning correctly.

[0052] Method 800 may include, in step 818, performing one or more verifications before administering an intravitreal injection. In some embodiments, some or all of steps 802–812 may be repeated until these verifications are successful or Method 800 is terminated by the patient or observer. Verifications may include, in step 814, verifying that permission has been received from a remote observer, and in step 816, verifying that gaze is maintained by the eye 108 being treated. For example, step 816 may include using video feeds from one or more cameras 318 to verify that the movement of the eye 108 being treated is below a maximum threshold, e.g., less than 1 degree, 0.5 degrees, or 0.1 degrees. Step 816 may include verifying the gaze of the eye 108 being treated (e.g., movement below the maximum threshold) for a minimum period of time, such as 1–3 seconds. Other verifications may include verifying the patient's identity by verifying that the iris or retina in one or more images from one or more cameras 318 matches one or more reference images or representations thereof of the iris and / or retina accessed by the controller. In some embodiments, the patient must give an explicit instruction to verify that step 818 is performable, such as by pressing or releasing a button, giving a verbal command, or making a visible gesture detected by a camera coupled to the controller 110.

[0053] Performing the intravitreal injection in step 818 may include activating the actuator 406 to drive the needle into the eye 108 to be treated, and activating the plunger actuator 504 or pump 526 to push the fluid through the needle into the eye 108. Step 818 may be performed simultaneously with one or more actions, which may include verifying continuous permission by a remote observer. For example, a remote observer may continuously receive video feeds from one or more cameras 318. The remote observer may keep the button pressed throughout the procedure and release it when the remote observer is convinced that the intravitreal injection should be stopped. In response to receiving notification that the button has been released, the controller 110 may stop the intravitreal injection. This technique of continuous permission is illustrative, and other techniques may be used, such as the remote observer pressing a button or manipulating other user interface elements to send an instruction to the controller 110 to stop the intravitreal injection. Step 818 may also be terminated in response to input from the patient, such as pressing or releasing a button, giving a verbal command, or making a visible gesture detected by a camera coupled to the controller 110.

[0054] Similarly, as previously stated with respect to step 816, gaze may be continuously evaluated. If gaze is not maintained, intravitreal injection may be discontinued. The IOP in the eye 108 being treated may be evaluated using the output of the IOP sensor 322. If the IOP rises faster than the prescribed rate or exceeds the prescribed pressure, intravitreal injection may be discontinued or the rate of drug delivery may be slowed. In some embodiments, the fluid injection rate is adjusted based on feedback regarding the IOP, thereby keeping the pressure in the eye 108 below a threshold or pressure-time curve, with time measured from the time the fluid injection began.

[0055] In some embodiments, the staging assembly 312 may be activated during step 818 to at least partially compensate for the movement of the needle of the eye 108 being treated. For example, the staging assembly 312 may include one or more strain sensors that sense the strain of the needle in one or more dimensions. The controller 110 may activate one or more of the linear actuators 402, 404, and 406 to reduce the amount of strain sensed by the strain sensors. Step 818 may be stopped in response that the movement of the eye 108 being treated has exceeded the range of motion and / or velocity of motion required for the staging assembly 312 to compensate for the movement of the eye 106.

[0056] Discontinuing an intravitreal injection may involve causing the actuator 406 to quickly withdraw the needle of the injection assembly 316 from the treated eye 108 to a safe distance. Once discontinued, the controller 110 may require repetition of methods 700 and 800. Alternatively, upon discontinuation, the controller 110 may prevent further intravitreal injections and require the patient to visit a healthcare professional for further intravitreal injections.

[0057] Step 818 may include monitoring the amount of drug delivered, for example, the amount the syringe plunger is pushed down, or the amount dispensed by the pump 526. Thus, the amount of drug remaining to be administered can be identified by the controller 110 and provided to the remote observer, or used by the controller 110 to control the amount of drug delivered in subsequent iterations of method 800.

[0058] Once methods 700 and 800 have been performed on one eye 108 to be treated, methods 700 and 800 may be repeated for the other eye 108 of the patient. As previously stated, one or more components may be moved, for example, the staging assembly 312 may be moved manually or automatically to a different mounting structure 302, and the staging assembly 312 may be fixed to that different mounting structure 302. As also previously stated, separate staging assemblies 312 may be used. Thus, the injection assembly 316 may be fixed to each staging assembly 312, and methods 700 and 800 may be performed sequentially, in parallel, or alternately for each eye 108 of the patient. For example, the administration of disinfectants and anesthetics may be performed in parallel for both eyes 108, while fixation and injection (e.g., steps 814-818) may be performed sequentially.

[0059] Methods 700 and 800 are illustrative and may be modified to perform additional steps or ophthalmic treatments. For example, while drugs, anesthetics, and disinfectants have already been described, other fluids may also be used to treat the eye 108 either before or after the injection. For example, some or all of a cooling spray (e.g., saline), anti-inflammatory cream or spray, and hemostatic solution may also be filled into the injection assembly 316 and applied using the injection assembly 316. In some embodiments, the staging assembly 312 may include one or more actuators operated by a controller to press a pad (e.g., cotton or other absorbent material) against the injection site after the injection to suppress bleeding. Similarly, an actuated pad incorporated into the staging assembly 312 may be pressed against the eye 108 during the injection to resist eye movement.

[0060] Additional matters The above description is provided so that those skilled in the art can implement the various embodiments described herein. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may also apply to other embodiments. For example, changes to the function and arrangement of the elements described above may be made without departing from the scope of this disclosure. Various procedures or components may be omitted, replaced or added as appropriate in various examples. Also, features described in some examples may be combined with any other example. For example, an apparatus may be implemented or a method may be performed using any number of the embodiments described herein. In addition, the scope of this disclosure shall also include apparatus or methods implemented using structures, functions or structures and functions that are added to or other than the various embodiments of this disclosure described herein. It should be understood that any embodiment of this disclosure disclosed herein may be embodied by one or more elements of the claims.

[0061] As used herein, the phrase “at least one of” in any list of items refers to any combination of those items, including a single member. For example, “at least one of a, b, or c” includes a, b, c, ab, ac, bc, and abc, as well as any combination of multiple identical elements (e.g., aa, aaa, aab, aac, abb, acc, bb, bbb, bbc, cc, and ccc, or any other sequence of a, b, and c).

[0062] As used herein, the term “identify” encompasses a wide range of actions. For example, “identify” may include calculating, calculating, processing, deriving, investigating, searching (e.g., searching in a table, database, or other data structure), confirming, etc. It may also include receiving (e.g., receiving information), accessing (e.g., accessing data in memory), etc. It may also include resolving, selecting, choosing, confirming, etc.

[0063] The methods disclosed herein include one or more steps or operations for implementing the method. The steps and / or operations of the method may be interchangeable with one another without departing from the claims. In other words, unless a specific order of steps or operations is specified, the specific order and / or use of the steps and / or operations may be modified without departing from the claims. Furthermore, the various operations of the method described above may also be performed by any suitable means capable of performing the corresponding function. These means may include, but are not limited to, various hardware and / or software components and / or modules, including circuits, application-specific integrated circuits (ASICs) or processors. Generally, where operations are shown in the drawings, these operations may have corresponding means-plus-function elements with similar numbering.

[0064] The various exemplary logic blocks, modules, and circuits described in connection with this disclosure may be implemented or run by a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic element (PLD), discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. The general-purpose processor may be a microprocessor, but alternatively, the processor may be any commercially available processor, controller, microcontroller, or state machine. The processor may also be implemented as a combination of computing devices, such as a DSP and a microprocessor, multiple microprocessors, a combination of a DSP core and one or more microprocessors working together, or any other such configuration.

[0065] The processing system may be implemented using a bus architecture. The bus may include any number of interconnection buses and bridges, depending on the specific application and overall design constraints of the processing system. The bus may interconnect various circuits, including, among others, processors, machine-readable media, and input / output devices. User interfaces (e.g., keypads, displays, mice, joysticks, etc.) may also be connected to the bus. The bus may also connect various other circuits, such as timing sources, peripherals, voltage regulators, and power management circuits, which are well known in the art and will not be described further. The processor may be implemented using one or more general-purpose and / or dedicated processors. Examples include microprocessors, microcontrollers, DSP processors, and other software-executable circuits. Those skilled in the art will understand how to optimally implement the described functions of the processing system, depending on the specific application and the overall design constraints imposed on the system as a whole.

[0066] When implemented in software, these functions may be stored or transmitted as one or more instructions or code in a computer-readable medium. Software, regardless of the term used—software, firmware, middleware, microcode, hardware description language, or otherwise—is broadly interpreted to mean instructions, data, or any combination thereof. Computer-readable medium includes both computer storage and communication media, such as any medium that facilitates the transfer of computer programs from one location to another. A processor may be responsible for managing buses and general operations, including the execution of software modules stored in computer-readable storage media. Computer-readable storage media may be coupled to the processor so that the processor can read information from and write information to the storage media. Alternatively, storage media may be incorporated into the processor. For example, computer-readable medium may include computer-readable storage media where instructions are stored separately from transmission lines, data-modulated carriers, and / or wireless nodes, all of which may be accessed by the processor via a bus interface. Alternatively or additionally, computer-readable medium or any part thereof may be incorporated into the processor, as in the case of caches and / or general-purpose register files. Examples of machine-readable storage media include, for example, RAM (random access memory), flash memory, ROM (read-only memory), PROM (programmable read-only memory), EPROM (erasable programmable read-only memory), EEPROM (electrically erasable programmable read-only memory), registers, magnetic disks, optical disks, hard drives, or any other suitable storage media or any combination thereof. Machine-readable media can be embodied in computer program products.

[0067] A software module may contain a single instruction or a number of instructions and may be distributed across several different code segments, different programs, and multiple storage media. A computer-readable medium may contain many software modules. When executed by a device such as a processor, a software module contains instructions that cause the processing system to perform various functions. A software module may include transmit modules and receive modules. Each software module may reside in a single storage device or be distributed across multiple storage devices. For example, when a trigger event occurs, a software module may be loaded from the hard drive into RAM. While a software module is executing, the processor may load some of the instructions into a cache to increase access speed. Thus, one or more cache lines may be loaded into a general-purpose register file to be executed by the processor. When referring to the functionality of a software module, it should be understood that such functionality is realized by the processor when executing instructions from that software module.

[0068] The following claims are not limited to the embodiments shown herein and shall be consistent with the entire scope of the claims as consistent with the language of the claims. Where an element is referred to in the singular in a claim, unless otherwise specifically stated, it shall mean "one or more" and not "only one". Unless otherwise specifically stated, the term "several" refers to one or more. No element of a claim shall be construed under Section 112(f) of the U.S. Patent Act unless it is expressly described using the phrase "means for..." or, in the case of a method claim, using the phrase "steps for...". All structural and functional equivalents of elements of various forms described throughout this disclosure, known to those skilled in the art or to be known thereafter, are expressly incorporated by reference herein and incorporated into the claims. Furthermore, nothing disclosed herein, whether such disclosure is expressly stated in the claims or not, is made available to the public.

[0069] Exemplary Embodiments Embodiment 1: A drug delivery method comprising positioning a portion of a patient's head within a drug delivery assembly, the assembly including one or more imaging devices configured so that the patient's eye is within its field of view, an injection assembly configured to receive a drug to be injected into the patient's eye, and a staging assembly comprising one or more actuators configured to position the injection assembly relative to the patient's eye; receiving one or more images from one or more imaging devices by a controller; detecting the position of the limbus of the patient's eye in one or more images by the controller; and operating one or more actuators by the controller to drive a needle attached to the injection assembly into the implantation position of the patient's eye according to the position of the limbus.

[0070] Embodiment 2: The method of Embodiment 1, further comprising activating one or more actuators in response to the controller verifying the patient's eye gaze to drive the needle into the implantation position.

[0071] Embodiment 3: The method of Embodiment 2, further comprising using a controller to activate a fixation target configured to be focused by the patient's eye.

[0072] Embodiment 4: The method of Embodiment 1, further comprising attaching a staging assembly to a first mounting structure of a drug delivery assembly, and attaching a staging assembly to a second mounting structure of a drug delivery assembly.

[0073] Embodiment 5: The method of Embodiment 1, wherein the staging assembly includes only linear actuators.

[0074] Embodiment 6: The method of Embodiment 1, wherein the drug delivery assembly is attached to one of (a) a support configured to rest on a support surface, and (b) a helmet configured to be worn on the patient's head.

Claims

1. A drug delivery device, wherein the drug delivery device is A drug delivery assembly configured to receive a portion of a patient's head, One or more imaging devices configured to bring the patient's eye into their field of view, An injection assembly configured to receive a drug to be injected into the eye of the patient, A staging assembly comprising one or more actuators, configured to position the injection assembly relative to the eye of the patient, A drug delivery assembly including, A controller coupled to one or more imaging devices and the staging assembly, Receiving one or more images from one or more imaging devices, The position of the limbus of the cornea of ​​the patient's eye in one or more of the aforementioned images is detected. A controller configured to actuate one or more actuators so that a needle attached to the injection assembly is driven into the implantation position in the patient's eye according to the position of the limbus, Drug delivery device.

2. The drug delivery device according to claim 1, wherein the controller is coupled to the injection assembly, and the controller is further configured to actuate the injection assembly so that the fluid is pushed through the needle into the eye of the patient.

3. The drug delivery device according to claim 2, wherein the injection assembly includes a pump.

4. The drug delivery device according to claim 2, wherein the injection assembly is configured to push down the plunger of a syringe placed within the injection assembly.

5. The drug delivery device according to claim 1, wherein the controller is further configured to activate one or more actuators in response to permission received from a remote operator on a network so that the needle is driven into the implantation position.

6. The drug delivery device according to claim 1, wherein the controller is further configured to activate one or more actuators in response to verification that the patient's gaze has been confirmed, so that the needle is driven into the implantation position.

7. The drug delivery device according to claim 6, further comprising a fixation target configured to be focused by the eye of the patient.

8. The drug delivery device according to claim 1, wherein the drug delivery assembly includes first and second mounting structures, and the staging assembly is configured to be attached to either of the first and second mounting structures.

9. The drug delivery device according to claim 1, wherein the staging assembly comprises only a linear actuator.

10. The drug delivery device according to claim 1, wherein the drug delivery assembly is attached to one of (a) a support configured to rest on a support surface and (b) a helmet configured to be worn on the head of the patient.

11. A method of delivering drugs, Part of the patient's head, One or more imaging devices configured to bring the patient's eye into their field of view, An injection assembly configured to receive a drug to be injected into the eye of the patient, A staging assembly comprising one or more actuators, configured to position the injection assembly relative to the eye of the patient, Positioning within a drug delivery assembly that includes, The controller receives one or more images from the one or more imaging devices, The controller detects the position of the limbus of the patient's eye in one or more images, The controller operates one or more actuators to drive the needle attached to the injection assembly into the implantation position in the patient's eye according to the position of the limbus, Methods that include...

12. The method according to claim 11, further comprising using the controller to activate the injection assembly so that fluid is injected through the needle into the eye of the patient.

13. The method according to claim 12, wherein activating the injection assembly includes activating the pump of the injection assembly.

14. The method according to claim 12, wherein activating the injection assembly includes pushing down the plunger of a syringe located within the injection assembly.

15. The method according to claim 11, further comprising the controller activating one or more actuators in response to permission received from a remote operator on a network so that the needle is driven into the retention position.

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