Abstract: An apparatus to treat a patient comprises a container to receive fluid of a device implanted in the eye. The fluid of the device can be analyzed to determine a component of the vitreous humor of the eye.

Abstract: Methods and apparatus provide a therapeutic fluid to devices implanted in the body, for example to containers of devices implanted in the eye of a patient. The methods and apparatus may comprise an injector to increase an amount of therapeutic agent injected into the device implanted in the eye, or a structure to receive the therapeutic fluid within the device implanted in the eye, or combinations thereof. The device implanted in the eye may comprise a reservoir chamber having a fluid with a density different than the therapeutic fluid, and the apparatus can be adapted to at least partially separate the implanted device fluid from therapeutic fluid within the reservoir chamber to increase and amount of therapeutic fluid placed in the reservoir chamber.

Abstract: Methods and apparatus provide treatment with a first therapeutic agent and a second therapeutic agent for an extended time. The first therapeutic agent may comprise a VEGF inhibitor and the second therapeutic agent may comprise an antiinflammatory, such as a non-steroidal anti-inflammatory, for example a cyclooxygenase inhibitor. One or more of the first therapeutic agent or the second therapeutic agent can be injected into the eye, for example injected into a therapeutic device implanted into the eye to release the injected therapeutic agent for an extended time.

Abstract: A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. A plurality of interconnecting channels can extend from the first side to the second side so as to connect a first a plurality of openings on the first side with a second plurality of openings on the second side.

Abstract: An implantable device having a reservoir for the sustained release of therapeutic agents. The device is configured to be at least partially implanted in an eye and include a retention structure and a penetrable element coupled to and extending within at least a portion of the proximal end region of the device. The device includes a porous drug release element is positioned in fluid communication with an outlet of the device and a reservoir having a volume configured to contain one or more therapeutic agents in fluid communication with the outlet through the porous drug release element. The device is at least partially inserted along an axis of insertion.

Abstract: Described are implantable therapeutic devices, systems and methods to treat a patient. The device includes a hollow refillable housing for implantation within the posterior segment of an eye through a penetration in the sclera including a proximal retention structure protruding outward from a proximal end region of the housing, an access portion opening, and a penetrable barrier positioned at least in part within the access portion opening, the penetrable barrier configured to be repeatedly penetrated. A rigid porous structure is positioned within a region of the housing away from the access portion opening into a reservoir chamber extends along an axis between the penetrable barrier and the porous structure includes a volume sized to deliver therapeutic amounts of a therapeutic agent to the eye for an extended period of time. A cover is coupled to at least an upper surface of the proximal retention structure.

Abstract: A therapeutic device for extended release drug delivery including a refillable reservoir configured to receive a therapeutic agent and having an outlet for delivery of the therapeutic agent to a patient from the reservoir over an extended period. A porous structure is coupled near the outlet of the reservoir, the porous structure formed of sintered material. A barrier layer is coupled to the reservoir on or adjacent a surface of the porous structure such that the therapeutic agent passes through both the porous structure and the barrier layer upon delivery from the reservoir through the outlet. The porous structure is tuned to deliver the therapeutic agent at a diffusion rate and the barrier layer is adapted to block passage of particles having an average particle size within an average particle size range that is outside an average particle size range blocked by the porous structure. Related methods and systems are provided.

Abstract: A device for injecting a therapeutic agent into an ocular implant at least partially implanted in an eye including an injection lumen providing a pathway for injecting the therapeutic agent into the implant; an outlet lumen providing a pathway for pre-existing fluid in the ocular implant to exit the implant; and a collection chamber fluidly coupled to the outlet lumen that provides a first fluid outflow resistance and a second fluid outflow resistance. The first fluid outflow resistance is lower than a first resistance to outflow of the implant. The second fluid outflow resistance is greater than a force imparted onto the implant by intraocular pressure of the eye. Injection of therapeutic agent into the implant via the injection lumen causes the pre-existing fluid to exit the implant and enter the collection chamber via the outlet lumen and causes a second pre-existing fluid to displace from the collection chamber.

Abstract: An ocular implant system including an ocular implant sized and shaped to be inserted at least partially into an eye; a carrier member with a shell having a central channel extending at least partially through the shell from a proximal end towards a distal end of the shell. A guide sleeve removably attached within at least a first region of the central channel of the shell and defining a proximal port into the central channel that is accessible from the proximal end of the shell. An implant holder removably attached within at least a second region of the central channel of the shell adjacent to a distal end of the guide sleeve and having a pair of graspers adapted to releasably secure the implant at a distal end of the implant holder. Related devices, systems, and/or methods are described.

Abstract: Described are implantable devices having expandable reservoirs for the sustained release of therapeutic agents. The device is configured to be at least partially implanted in an eye and includes a retention structure and a penetrable element coupled to and extending within at least a portion of the retention structure. A porous drug release mechanism is positioned in fluid communication with an outlet of the device; and a reservoir having a volume configured to contain one or more therapeutic agents is in fluid communication with the outlet through the porous drug release mechanism. The device is at least partially inserted along an axis of insertion. The reservoir enlarges from an insertion configuration having a first three-dimensional shape to an expanded configuration having a second three-dimensional shape, the second three-dimensional shape being eccentrically positioned relative to the axis of insertion.

Abstract: An injectable formulation of therapeutic agent may comprise the therapeutic agent and a stabilizer such that a substantial portion of the stabilizer remains in the therapeutic device to stabilize the therapeutic agent when the therapeutic agent is released from the therapeutic device. The injectable formulation may comprise one or more of binding agent particles or erodible material particles, such that the formulation can be injected into the therapeutic device. The binding agent particles can bind reversibly to the therapeutic agent so as to modulate release of the therapeutic agent, and the erodible material particles can generate protons of an acid so as to increase stability of the therapeutic agent and may modulate release of the therapeutic agent. The therapeutic agent can be combined with one or more of the stabilizer, the binding agent particles or the erodible particles to increase stability of the therapeutic agent and may modulate release.

Abstract: A therapeutic device for extended release drug delivery including a refillable reservoir configured to receive a therapeutic agent and having an outlet for delivery of the therapeutic agent to a patient from the reservoir over an extended period. A porous structure is coupled near the outlet of the reservoir, the porous structure formed of sintered material. A barrier layer is coupled to the reservoir on or adjacent a surface of the porous structure such that the therapeutic agent passes through both the porous structure and the barrier layer upon delivery from the reservoir through the outlet. The porous structure is tuned to deliver the therapeutic agent at a diffusion rate and the barrier layer is adapted to block passage of particles having an average particle size within an average particle size range that is outside an average particle size range blocked by the porous structure. Related methods and systems are provided.

Abstract: An injectable formulation of therapeutic agent may comprise the therapeutic agent and a stabilizer such that a substantial portion of the stabilizer remains in the therapeutic device to stabilize the therapeutic agent when the therapeutic agent is released from the therapeutic device. The injectable formulation may comprise one or more of binding agent particles or erodible material particles, such that the formulation can be injected into the therapeutic device. The binding agent particles can bind reversibly to the therapeutic agent so as to modulate release of the therapeutic agent, and the erodible material particles can generate protons of an acid so as to increase stability of the therapeutic agent and may modulate release of the therapeutic agent. The therapeutic agent can be combined with one or more of the stabilizer, the binding agent particles or the erodible particles to increase stability of the therapeutic agent and may modulate release.

Abstract: A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. The length of the channels extending from the first side to the second side may comprise an effective length greater than a distance across the porous structure from the first side to the second side. The therapeutic device may comprise a penetrable barrier to inject therapeutic agent into the device when implanted in the patient.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. A plurality of interconnecting channels can extend from the first side to the second side so as to connect a first a plurality of openings on the first side with a second plurality of openings on the second side.

Abstract: An injector apparatus comprises an elongate structure having one or more openings positionable near a penetrable barrier of an implantable device so as to receive fluid of the implantable device. The apparatus comprises a needle and a sheath extending over at least a portion of the needle. The elongate structure may comprise a distal tip to penetrate tissue and the penetrable barrier, and a distal opening near the tip to release therapeutic fluid into the implantable chamber. In many embodiments the distal tip, the distal opening, and the plurality of openings are separated from a stop that engages a tissue of the patient and limit penetration depth such that the distal opening and the plurality of openings are located along an axis of the implantable device to increase an efficiency of the exchange.

Abstract: Methods and apparatus provide treatment with a first therapeutic agent and a second therapeutic agent for an extended time. The first therapeutic agent may comprise a VEGF inhibitor and the second therapeutic agent may comprise an antiinflammatory, such as a non-steroidal anti-inflammatory, for example a cyclooxygenase inhibitor. One or more of the first therapeutic agent or the second therapeutic agent can be injected into the eye, for example injected into a therapeutic device implanted into the eye to release the injected therapeutic agent for an extended time.

Abstract: Described herein is an apparatus to insert an implantable therapeutic device into a patient. The apparatus includes a proximal handle and a distal placement portion coupled to the proximal handle and configured to hold the implantable therapeutic device. The distal placement portion includes a first side having a first engagement structure at a distal end of the first side, the first engagement structure configured to surround at least a first portion of a proximal end region of the implantable therapeutic device. The distal placement portion includes a second, opposite side having a second engagement structure at a distal end of the second side, the second engagement structure configured to surround at least a second, opposite portion of the proximal end region of the implantable therapeutic device.

Abstract: Described are implantable devices having expandable reservoirs for the sustained release of therapeutic agents. The device is configured to be at least partially implanted in an eye and includes a retention structure and a penetrable element coupled to and extending within at least a portion of the retention structure. A porous drug release mechanism is positioned in fluid communication with an outlet of the device; and a reservoir having a volume configured to contain one or more therapeutic agents is in fluid communication with the outlet through the porous drug release mechanism. The device is at least partially inserted along an axis of insertion. The reservoir enlarges from an insertion configuration having a first three-dimensional shape to an expanded configuration having a second three-dimensional shape, the second three-dimensional shape being eccentrically positioned relative to the axis of insertion.