U.S. patent application number 17/208235 was filed with the patent office on 2022-03-03 for device for ocular access.
The applicant listed for this patent is CLEARSIDE BIOMEDICAL, INC.. Invention is credited to Stanley R. CONSTON, Amy Lee HAMMACK, Ronald YAMAMOTO.
Application Number | 20220062040 17/208235 |
Document ID | / |
Family ID | |
Filed Date | 2022-03-03 |
United States Patent
Application |
20220062040 |
Kind Code |
A1 |
HAMMACK; Amy Lee ; et
al. |
March 3, 2022 |
DEVICE FOR OCULAR ACCESS
Abstract
The present invention provides devices to access the
suprachoroidal space or sub-retinal space in an eye via a minimally
invasive transconjunctival approach. The devices may also be used
after a partial dissection, for example after dissection of the
outer scleral layer of the eye, and using the device within the
dissection to access the suprachoroidal space or the sub-retinal
space.
Inventors: |
HAMMACK; Amy Lee; (Santa
Clara, CA) ; CONSTON; Stanley R.; (San Carlos,
CA) ; YAMAMOTO; Ronald; (San Francisco, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CLEARSIDE BIOMEDICAL, INC. |
Alpharetta |
GA |
US |
|
|
Appl. No.: |
17/208235 |
Filed: |
March 22, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15872206 |
Jan 16, 2018 |
10952894 |
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17208235 |
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14821310 |
Aug 7, 2015 |
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15872206 |
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13273775 |
Oct 14, 2011 |
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14821310 |
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61393741 |
Oct 15, 2010 |
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International
Class: |
A61F 9/00 20060101
A61F009/00; A61F 9/007 20060101 A61F009/007; A61M 5/46 20060101
A61M005/46; A61M 5/48 20060101 A61M005/48 |
Claims
1-11. (canceled)
12. An apparatus, comprising: a body defining a passageway
configured to receive a puncture member therethrough; the puncture
member coupled to and disposed within the passageway of the body,
the puncture member configured to define a delivery passageway
within a sclera of an eye through which a substance can be conveyed
to a suprachoroidal space (SCS) of an eye, the puncture member
defining a lumen therethrough; and an elongate member slidably
disposed within a lumen of the puncture member, the elongate member
configured to be advanced distally through and beyond the lumen of
the puncture member to displace a choroid of the eye relative to a
sclera of the eye to at least one of create or expand the SCS, the
elongate member configured to be withdrawn into the lumen of the
puncture member with a distal end of the puncture member disposed
within the SCS such that a therapeutic substance can be delivered
through the lumen of the puncture member and into the SCS.
13. The apparatus of claim 12, further comprising a stopper coupled
to the puncture member and configured to control a depth of entry
of the puncture member into the eye.
14. The apparatus of claim 12, wherein the elongate member is a
wire.
15. The apparatus of claim 14, wherein a distal end of the wire is
rounded.
16. The apparatus of claim 12, wherein the puncture member is a
hollow needle.
17. The apparatus of claim 12, wherein the elongate member has a
blunt tip.
18. An apparatus, comprising: a body defining a passageway
configured to receive a puncture member therethrough; the puncture
member coupled to and disposed within the passageway of the body,
the puncture member configured to define a delivery passageway
within a first tissue layer of an eye through which a substance can
be conveyed to target region within the eye, the puncture member
defining a lumen therethrough; and an elongate member slidably
disposed within a lumen of the puncture member, the elongate member
configured to be advanced distally through and beyond the lumen of
the puncture member to displace a second tissue layer of the eye
relative to the first tissue layer to at least one of create or
expand the target region, the elongate member configured to be
withdrawn into the lumen of the puncture member with a distal end
of the puncture member disposed within the target region such that
a therapeutic substance can be delivered through the lumen of the
puncture member and into the target region, a distal end of the
elongate member being blunt.
19. The apparatus of claim 18, further comprising a stopper coupled
to the puncture member and configured to control a depth of entry
of the puncture member into the eye.
20. The apparatus of claim 18, wherein the elongate member is a
wire.
21. The apparatus of claim 20, wherein the distal end of the wire
is rounded.
22. The apparatus of claim 18, wherein the puncture member is a
hollow needle.
23. The apparatus of claim 18, wherein the first tissue layer is a
sclera of the eye, the second tissue layer is a choroid of the eye,
and a target region is the suprachoroidal space of the eye.
24. The apparatus of claim 18, wherein the target region is a
subretinal space of the eye.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/872,206, entitled "Device for Ocular
Access," filed Jan. 16, 2018, which is a continuation of U.S.
patent application Ser. No. 14/821,310, entitled "Device for Ocular
Access," filed Aug. 7, 2015, which is a continuation of U.S. patent
application Ser. No. 13/273,775, entitled "Device for Ocular
Access," filed Oct. 14, 2011, which claims priority to U.S.
Provisional Application Ser. No. 61/393,741, entitled "Device for
Ocular Access," filed Oct. 15, 2010, the entirety of each of which
is incorporated herein by reference.
BACKGROUND OF INVENTION
[0002] The suprachoroidal space is a potential space in the eye
that is located between the choroid, which is the middle layer or
vascular tunic of the eye, and the sclera, the outer (white) layer
of the eye. The suprachoroidal space extends from the anterior
portion of the eye near the ciliary body to the posterior end of
the eye adjacent to the optic nerve. Normally the suprachoroidal
space is not evident due to the close apposition of the choroid to
the sclera from the intraocular pressure of the eye. Since there is
no substantial attachment of the choroid to the sclera, the tissues
can separate to form the suprachoroidal space when fluid
accumulation or other conditions occur. The suprachoroidal space
provides a potential route of access from the anterior region of
the eye to the posterior region for the delivery of treatments for
diseases of the eye. Standard surgical access to the suprachoroidal
space is achieved through incisions in the conjunctiva and the
sclera, and is primarily performed in an operating room. Surgical
access is useful in draining choroidal effusions or hemorrhage, and
in placing microcatheters and cannulas into the suprachoroidal
space for delivery of agents to the back of the eye. Treatments for
diseases such as age-related macular degeneration, macular edema,
diabetic retinopathy and uveitis may be treated by the appropriate
active agent administered in the suprachoroidal space.
[0003] The sub-retinal space is a potential space in the eye that
is located between the sensory retina and the choroid. The
sub-retinal space lies under all portions of the retina, from the
macular region near the posterior pole to the ora serrata, the
anterior border of the retina. Normally the sub-retinal space is
not evident as the retina needs to be apposed to the underlying
choroid for normal health and function. In some disease states or
as a result of trauma, a retinal detachment may occur, forming a
fluid filled region in the sub-retinal space. Such spaces normally
require treatment to reattach the retina before retinal function is
irreversibly lost. However, it has been found that some treatments
such as gene therapy or cell therapeutics may be applied to the
sub-retinal space to provide maximum exposure to the retina. In a
normally functioning retina, small injections in the sub-retinal
space create a small area of retinal detachment which resolves in a
short period of time, allowing direct treatment of the retina.
[0004] The sub-retinal space may be accessed ab-interno by piercing
a small gauge needle through the retina. This procedure involves
penetration of the intraocular space of the eye and forming a small
retinotomy by the needle. A therapeutic agent injected into the
sub-retinal space may flow out through the retinotomy into the
vitreous cavity causing exposure of the therapeutic to the lens,
ciliary body and cornea as it exits through the anterior aqueous
outflow pathway.
[0005] It is desired to have a method whereby the suprachoroidal
space or the sub-retinal space may be accessed in a minimally
invasive method via an ab-externo transconjunctival approach. Such
a method would provide a method to limit, guide or guard the
penetration of a needle device into the suprachoroidal space or
sub-retinal space to prevent further penetration. The present
invention provides an apparatus to allow minimally invasive,
transconjunctival access to the suprachoroidal space or sub-retinal
space in the eye for the delivery of therapeutic or diagnostic
materials.
SUMMARY OF THE INVENTION
[0006] The present invention provides a device comprising an
elongated body having a distal end and proximal end, said ends in
communication through an internal pathway within the body
wherein:
[0007] the distal end is configured with a sharp edge or point to
penetrate into ocular tissues of the outer shell of the eye,
[0008] a moveable guarding element disposed in a first
configuration to shield the ocular tissues from the sharp edge or
point, and adapted to apply a distally directed force to the
tissues at the distal end of the device to displace tissue away
from the distal end of the device upon entry into the
suprachoroidal space or subretinal space in an eye with the distal
end; wherein the guarding element is moveable to a second
configuration to expose said sharp edge or point to said tissues
for penetration into the tissues,
[0009] and an access port to deliver materials and substances
through the pathway in the elongated body after deployment of the
guarding element within the suprachoroidal space or subretinal
space.
[0010] In some embodiments the guarding element is attached to a
spring or compressible element that upon compression thereof
provides a distally directed force on the guarding element.
[0011] In some embodiments the guarding element comprises a
flowable material selected from a fluid or gas that is directed to
flow out of the distal end of the device to provide a distally
directed force.
[0012] In some embodiments the device further comprises a sealing
element attached at the distal end of the elongated body adapted to
reduce or prevent leakage of fluid or gas through a tissue tract
created by the device.
[0013] In some embodiments the device accommodates a spring to
apply a distal force on the sealing element to provide a sealing
force of the element against the eye tissue.
[0014] In some embodiments the device comprises a reservoir at the
proximal end for receiving a material to be delivered at the target
space and the sealing element is in mechanical communication with
an activating element for releasing the material from the
reservoir.
[0015] In some embodiments the device comprises an associated
sealing element adapted for retention on the surface of the eye to
receive the distal end of the device to locate and stabilize the
device during penetration into the eye.
[0016] The invention further provides a device for placement in the
sclera of an eye, comprising a body having a proximal end adapted
for location at or near the scleral surface and a distal end
adapted for location within the suprachoroidal or subretinal space,
where the device comprises a lumen and a mechanical stop at the
proximal end for retaining the proximal end at or near the scleral
surface.
[0017] Methods of using the devices of the invention to access the
suprachoroidal or subretinal spaces of the eye are also
provided.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a schematic cross-section of the eye with a detail
view of the layers of the eye.
[0019] FIG. 2 is a schematic of a device according to one
embodiment of the invention comprising an angled tip.
[0020] FIG. 3 is a schematic of a device according to one
embodiment of the invention comprising a guard element disposed in
the lumen of the main shaft.
[0021] FIG. 4 is a schematic of a device according to one
embodiment of the invention comprising a tubular guard element
disposed about the outside of the main shaft.
[0022] FIG. 5 is a schematic of a device according to one
embodiment of the invention comprising a reservoir element.
[0023] FIG. 6 is a schematic of a device according to one
embodiment of the invention comprising a sealed reservoir activated
by piercing said seal.
[0024] FIG. 7 is a schematic of a device according to one
embodiment of the invention comprising a spring loaded distal
element on a sliding shaft with a valve mechanism.
[0025] FIG. 8 is a schematic of a device according to one
embodiment of the invention comprising a sliding distal element on
a sliding shaft with a valve mechanism.
[0026] FIG. 9 is a schematic of a device according to one
embodiment of the invention comprising a fixed shaft and a sliding
outer element connected to a valve mechanism.
[0027] FIG. 10 is a schematic of a device according to one
embodiment of the invention comprising a sealing element spring
loaded about a main shaft.
[0028] FIG. 11 is a schematic of a device according to one
embodiment of the invention comprising a separate sealing mechanism
disposed upon the surface of the tissues and an injecting element
inserted therethrough.
[0029] FIG. 12 is a schematic depiction of a device performing
injections into the suprachoroidal and subretinal spaces.
[0030] FIG. 13 is a schematic of a device according to one
embodiment of the invention comprising an access port on a
trocar.
[0031] FIG. 14 is a schematic depiction of an access port placed in
suprachoroidal space with a device.
[0032] FIG. 15 is a schematic depiction of a main shaft of a device
according to the invention with a beveled tip and the tissue
contacting surface of the device.
[0033] FIG. 16 is a graph of the results of the test described in
Example 13.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0034] The present invention provides methods and devices to access
the suprachoroidal space or sub-retinal space in an eye via a
minimally invasive transconjunctival approach to eliminate the need
for dissection and subsequent suture closure of the dissection. The
devices may also be used after a partial dissection, for example
after dissection of the outer scleral layer of the eye, whereby the
device is used within the dissection to access the suprachoroidal
space or the sub-retinal space. Specifically, the invention
provides devices that advantageously may be used in an operating
room- or treatment room based setting, to allow for the delivery of
substances to the suprachoroidal space or sub-retinal space. Of
particular utility is the use of the device to deliver drugs or
drug containing materials which provide sustained availability of
the drug to the eye. Drugs injected with the device to the
suprachoroidal space are useful for treating the choroid and
through the vasculature of the choroid, the inner tissues of the
eye. Drugs injected with the device to the sub-retinal space are
useful for treating the retinal pigment epithelia and the sensory
retina. Some examples include polymer drug release materials in the
form of injectable filaments or microspheres, or drugs with limited
solubility that would provide slow release of drug to the eye.
Limited solubility steroids such as triamcinolone acetonide or
loteprednol etabonate are steroids which may be injected into the
suprachoroidal in a suspension formulation.
[0035] The devices comprise an elongated body with a distal and a
proximal ends, where the device is held by the operator at the
proximal end. The distal end may be configured to penetrate the
conjunctiva and the sclera, but not the choroid to access the
suprachoroidal space. Alternatively, the distal end may be
configured to penetrate the conjunctiva, sclera, and the choroid
but not the retina to access the sub-retinal space. The device may
contain substances to be delivered through the distal end once
placed into the suprachoroidal or sub-retinal spaces.
Alternatively, the proximal end may be configured to receive
apparatus for the delivery of substances such as a syringe. The
devices may also be adapted to place a thin-walled sleeve, as a
port or introducer, into the suprachoroidal space or sub-retinal
space to allow for subsequent placement and advancement of cannulae
or catheters.
[0036] In certain preferred embodiments, the device is adapted to
limit penetration depth and/or to safely displace the choroid or
retina away from the overlying tissue, thereby allowing the distal
tip to penetrate into the suprachoroidal space or sub-retinal
space, but preventing the distal tip from penetrating or causing
damage to the choroid or retina itself. Displacement-limiting or
guarding elements may be provided through mechanical or fluidic
mechanisms to provide a forward (distally) directed force to the
tissues in the eye at the distal tip of the device. The guarding
elements may be self-activated by the device or manually activated
by the surgeon at the appropriate time. In conjunction with a
fluidic mechanism acting as a guarding element, the device may
incorporate a sealing element directed at the site of penetration
of the eye to prevent leakage of the fluidic element that might
cause undesired reduction of the degree of intended displacement of
the underlying choroid or retina.
[0037] As shown in FIG. 1, the eye 1 is a globe with two main
sections, the anterior segment containing the cornea 2, iris 3,
ciliary body 4 and lens 5; and the posterior segment containing the
choroid 6, retina 7 and vitreous 8. The outer shell of the eye is
comprised of four main layers, said layers from outside to inside
are: the conjunctiva, the thin, loosely adhered outer cover of the
eye; the sclera 9, the white collagenous tissue making up the major
structural component of the eye; the choroid 6, the vascular layer
of the eye; and the retina 7, the sensory layer of the eye. The two
targets being assessed by the invention are the potential space
between the sclera and the choroid, the suprachoroidal space 10,
and the potential space between the retina and the choroid, the
sub-retinal space 11.
[0038] In one embodiment (FIG. 2), the device according to the
invention comprises a main shaft 12 with a distal end and a
proximal end in internal communication with each other, such as,
through a lumen 15. The distal end may comprise a beveled,
sharpened tip 13 configured to penetrate ocular tissues with a
minimum amount of force to create a tract or passage in the sclera.
Tip 13 may comprise a point, a single bevel or multiple bevel
surfaces. Bevels (the angle swept by the surfaces with the pointed
tip at the apex) in the range of 10.degree.-30.degree. are
preferred. The proximal end may comprise attachment receiver 14
such as a female Luer connector to allow for attachment of a
syringe or other delivery apparatus. The main shaft 12 may comprise
a hollow tube with a lumen 15. The shaft may have an outer diameter
in the range of 41 gauge (0.0028 inch, 0.071 mm) to 20 gauge (0.035
inch, 0.89 mm) and an inner lumen diameter in the range of 0.002
inch (0.05 mm) to 0.023 inch (0.58 mm) The tube may comprise a
metal such as tungsten, Nitinol (nickel-titanium alloy) or
stainless steel; or a polymer such as polyetheretherketone (PEEK),
polycarbonate, nylon or other similar structural engineering
polymer. In one embodiment, the shaft may incorporate an angle or
bend 16 near the distal end. The angle or bend is used to direct
the distal tip from an initial approach perpendicular to the
surface which allows for case of entry, to a path which enters the
suprachoroidal space or sub-retinal space approximately tangential
to the curve of the eye. The bend angles may be in the range of
10.degree.-60.degree., and preferably in the range of
20.degree.-40.degree..
[0039] In another embodiment (FIG. 3), the shaft 12 may incorporate
a mechanical guard to displace the choroid or retina from the
sharpened distal tip. The mechanical guard may comprise an element
18 slideably disposed within the lumen 15 or an element disposed
outside the diameter of the shaft 12. In the first instance, the
guard 18 may comprise a blunt tip, elongated member 17, slideably
disposed within the lumen 15 of the main shaft, having the guard
distal tip extending beyond the distal tip of the main shaft and
connected to the body of the device by a compression spring 19. The
guard member 17 is spring loaded in a manner such that when the
blunt device tip encounters tissues with substantial mechanical
resistance, such as the sclera, the guard member is compressed
backwards into the lumen, exposing the sharpened tip of the device
and allowing it to penetrate tissues. During advancement within the
tissues with the sharpened tip, the spring provides a forward
directed force to the guard. When the distal tip encounters an open
space or tissues that may be displaced such as the choroid in the
case of the suprachoroidal space or the retina in the case of the
sub-retinal space, the guard member 17 again extends forward due to
the reduced resistance against the tip, ahead of the sharpened tip
of the device and thereby displacing the tissues away from the tip
of the device. The tissue displacement spring rate for the guard is
in the range of about 0.3 lb./in (0.05 N/mm) to 2.8 lb./in (0.50
N/mm) and preferably in the range of 4.6 lb./in (0.8 N/mm) to 1.4
lb./in (0.25 N/mm) The guard member may have a configuration to
allow the flow of fluid through the lumen of the main shaft once
the guard is deployed and the underlying tissue is displaced.
Alternatively, the guard may be configured as part of a removable
assembly such that once the sharpened tip is in the appropriate
space, the guard assembly may be removed and a delivery device,
such as a syringe may be attached to the proximal end to deliver a
fluid, therapeutic agent or diagnostic substance.
[0040] Referring to FIG. 4, the mechanical guard may comprise a
tube 20 slideably disposed on the outside of the main shaft 12,
which is also connected to the main shaft by a compressive element
21 such as a metallic or plastic spring, a polymer with elastic
properties or a compressible gas reservoir. The tube is sized and
configured to enter the tract or passage in the sclera with the
main shaft. The device is configured such that the compressive
element 21 exerts a force on the mechanical guard to provide a
forward directed force at the distal end. In a similar manner to
the previous embodiment described in connection with FIG. 3, when
the tubular guard encounters tissue with mechanical resistance
greater than the choroid or retina (e.g. sclera) the tube is
displaced backwards (in the proximal direction), exposing and
allowing the sharpened tip to penetrate the tissues. When the guard
enters the tissues and encounters an open space or soft tissue such
as the choroid or retina, it slides forward due to the reduced
resistance, effectively blocking the distal tip of the device from
further penetration.
[0041] In another embodiment, the guard may comprise a flowable or
fluidic guard, composed of either a fluid or gas, which is
delivered through the distal end of the device to provide a forward
directed force and displace the choroid as the device distal tip
enters the suprachoroidal space or the displacement of the retina
as the distal tip enters the sub-retinal space. The guard may
comprise a fluid, such as sterile water, saline, balanced salt
solution, silicone oil, surgical viscoelastic, polymer solution or
an ophthalmically acceptable perfluorocarbon fluid such as
perfluoro-n-octane. Alternately, the guard may comprise a gas, such
as air, nitrogen (N.sub.2), carbon dioxide (CO.sub.2), or gases
used in ophthalmology such as sulfur hexafluoride (SF.sub.6) or
octafluoropropane (C.sub.3F.sub.8). Additionally the guard may
comprise the fluid or gas of a therapeutic or diagnostic
formulation to be delivered. Fluid or gas volumes and pressures to
sufficiently displace the tissues without overinflating the eye but
allowing enough space to safely perform an injection are usefully
in the range of about 10 microliters to 500 microliters volume and
about 0.05 mm Hg to 52 mm Hg gauge pressures, and preferably in the
range of 50 microliters to 250 microliters volume and 4 mm Hg to 30
mm Hg gauge pressure. Such a fluidic guard may be delivered through
a syringe filled with the fluid or gas attached to the proximal
connector.
[0042] In another embodiment (FIG. 5), the device comprises a
pressurized reservoir 22 for the delivery of a precise amount of
the fluidic guard. The reservoir may be configured to deliver the
material at a precise pressure and flow rate to achieve
displacement of the choroid or retina, while preventing
over-inflation of the space. The reservoir may be adapted to be
prefilled to a desired volume and pressure. This may be
accomplished, for example, by incorporating entries 23 to fill the
reservoir, such as injection ports, valves, heat sealable caps or
similar entries to allow sterile transfer of materials to the
reservoir, which may be accomplished during the manufacture of the
device. The reservoir may further be adapted to allow controlled
access to the main shaft lumen to allow for the injection of the
contents of the reservoir to the target site. Access may be
achieved by a septum 24, seal or plug at the distal end of the
reservoir, configured to accommodate an activating mechanism of the
device. In another embodiment, the reservoir may be configured to
deliver a therapeutic or diagnostic substance with a flowable
material to act as a fluidic guard.
[0043] The device may be adapted to automatically activate the
delivery of the fluid or gas, or the delivery may be activated and
controlled by the user. Automatic delivery may be triggered by a
plate or stop, which, when the stop comes in contact with the
surface of the eye, triggers the delivery of the fluid or gas. In
one embodiment (FIG. 6) the stop may comprise a tubular element 25
disposed about the outside of the main shaft 12. The element 25 may
be attached to the main body by means of a compressive element 21
such as a metallic or plastic spring, a polymer with elastic
properties, or a compressible gas reservoir. The main shaft may
comprise the activating mechanism to release reservoir material.
The mechanism may comprise a sharpened tip 26 at the proximal end
of the main shaft configured to pierce a septum or seal 24 on the
reservoir 22.
[0044] In another embodiment (FIG. 7), the device comprises a main
shaft 12 with a distal, beveled tip 13 and a trigger stop 37
disposed about the shaft. The main shaft is disposed within a
proximal hub 38 containing a reservoir 22. The reservoir comprises
a check valve 27 and Luer connector 28 on the proximal end to
receive attachments to fill the reservoir. The distal end of the
reservoir contains a polymer septum 24. The proximal end 29 of the
main shaft is sealed and disposed through the septum. The proximal
end of the main shaft comprises a hole 30 or valve port on the
side, the port being distally displaced from the septum when the
device is not activated. The reservoir is prefilled with a guard
fluid or gas, or a therapeutic agent by a syringe or gas line
connection. A tubular element 25 is disposed about the outside of
the main shaft distal portion, the element attached to the main
shaft by a compression spring 21. The spring constant is in the
range of 0.29 lb./in (0.05 N/mm) to 14.3 lb./in (2.5 N/mm) and
preferably in the range of 0.97 lb./in (0.17 N/mm) to 3.37 lb./in
(0.59 N/mm) The device is adapted such that upon contact with the
surface of the eye, the distal tubular element 25 translates
rearward (in the proximal direction) compressing the spring element
against the trigger stop 37 until the force reaches a predetermined
value set by the spring rate and the coefficient of friction of the
septum against the main shaft. Upon reaching the appointed force
value, continued advancing pressure on the device hub translates
the main shaft rearwards, displacing the port 30 proximally to the
reservoir side of the septum 31, releasing the contents of the
reservoir to exit the distal tip. The trigger stop may also be
configured to limit the rearward travel of the main shaft beyond
the point where the reservoir contents are released. The force
value combination of spring rates and septum friction coefficients
may be selected to trigger at a specific penetration depth either
when entering the suprachoroidal space or the subretinal space. The
depth of penetration is in the range of about 0.02 inches (0.5 mm)
to 0.157 inches (4 mm).
[0045] In another embodiment (FIG. 8), the device comprises a main
shaft 12 with a distal, beveled tip 13 and a tubular trigger stop
39 disposed about the shaft. The trigger stop has an inner diameter
larger than the outer diameter of the main shaft and is attached to
the main shaft at the proximal end such that the gap between the
trigger stop and the main shaft faces toward the distal end. The
main shaft is disposed within a proximal hub 38 containing a
reservoir 22. The reservoir comprises a check valve 27 and Luer
connector 28 on the proximal end to receive attachments to fill the
reservoir. The distal end of the reservoir contains a polymer
septum 24. The proximal end 29 of the main shaft is sealed and
disposed through the septum. The proximal end of the main shaft
comprises a hole 30 or valve port on the side, the port being
distally displaced from the septum when the device is not
activated. The reservoir is prefilled with a guard fluid or gas, or
a therapeutic agent by a syringe or gas line connection. A tubular
element 25 is disposed about the outside of the main shaft distal
portion, the element 25 comprising a thicker walled distal portion
56 and a thin walled proximal portion 40. The thin walled portion
is sized to slide between the tubular trigger stop and the main
shaft. The device is adapted such that upon contact with the
surface of the eye, the distal tubular element 25 translates
rearward until the proximal end of the thick walled portion comes
in contact with the trigger stop 39. Continued advancing pressure
on the device hub translates the main shaft rearwards, displacing
the port 30 proximally to the reservoir side of the septum 31,
releasing the contents of the reservoir to the lumen of the main
shaft. The trigger stop may be configured to limit rearward travel.
The lengths of the device components and the gap between the distal
tubular element 25 and the trigger stop 39 are adapted to provide a
specific depth of penetration of the main shaft distal beveled tip
13.
[0046] The depth of penetration to enter the suprachoroidal or
subretinal space is in the range of about 0.02 inches (0.5 mm) to
0.157 inches (4 mm).
[0047] In another embodiment (FIG. 9), the device according to the
invention comprises a tubular distal shaft 41 with a distal beveled
tip 13 and tubular proximal shaft 42. The shafts 41, 42 are
slideably disposed with each other and one shaft may be sized so as
to slide inside or outside the other shaft. Proximal shaft 42
incorporates a sealed proximal end 29 and a hole or port 30 on the
side. An elastomer seal 43 is disposed about the outside of the
distal shaft 41 and proximal shaft 42, across the junction between
the two and provides a seal to prevent fluid or gas escape while
allowing linear motion between the shafts. The distal shaft is
fixed in place to a proximal hub 38, by way of a cross-bar 44. An
outer housing 45 is slideably disposed about the distal shaft and
is attached to the proximal shaft. The outer housing comprises a
slot or cut-out 46 to accommodate the cross-bar 44, allowing the
outer housing and proximal shaft to slide independently of the
fixed distal shaft 41. The proximal hub comprises a reservoir 22
with a polymer septum 24, a check valve 27 to allow pressurization
of the reservoir and Luer connector 28 at the proximal end to
receive attachments to fill the reservoir. The sealed proximal end
29 of the proximal shaft is disposed through the septum, such that
during filling of the reservoir, the port 30 is distally displaced
from the septum 24 thereby sealing the reservoir. The reservoir is
prefilled with a guard fluid or gas, or a therapeutic substance by
a syringe or gas line connection. The device is adapted such that
upon contact with a tissue surface of the distal tip of the outer
housing, the outer housing 45 and the proximal shaft 42 are
translated rearward (in the proximal direction) displacing the port
30 proximally to the reservoir side of the septum 24, releasing the
contents into the main shaft lumen.
[0048] In another embodiment (FIG. 10), in conjunction with a
fluidic guard, the device may also comprise a sealing element
directed at the site of conjunctiva and sclera penetration. The
seal is designed to prevent leakage of the fluid or gas through the
tissue tract created by the device which would reduce the amount of
fluid or gas directed at the underlying choroid or retina to
displace the underlying tissue to prevent penetration by the
pointed or beveled tip of the main shaft. The seal may be
incorporated on the device, for example as an outer tubular sleeve
47 slideably disposed over the main shaft 12 which incorporates a
beveled tip 13. The tubular sleeve incorporates an internal seal 48
to seal the sleeve against the main shaft to prevent fluid or gas
reflux between the sleeve and shaft. The proximal end of the main
shaft is disposed in a hub 38 comprising a Luer connector 28 for
attachment of a fluid or gas delivery mechanism such as a syringe.
The distal end of the sleeve acts to seal against the conjunctiva
at the surface of the eye or the scleral surface after minor
dissection. The tubular sleeve is preferred to have a diameter at
the tissue surface to provide sufficient area surrounding the site
of tissue penetration to provide an effective seal against the
pressure of the fluidic guard. The outer diameter of the tubular
sleeve may range from 0.04 inch (1.0 mm) to 0.12 inch (3.0 mm) to
provide adequate sealing area on the surface of the eye without
unduly obscuring the visualization of the site. The tubular sleeve
may be aided by a spring mechanism 21 to provide a sealing force
against the eye surface as the inner main shaft penetrates the
outer tissues of the eye. The spring constant is the range of 0.29
lb./in (0.05 N/mm) to 14.3 lb./in (2.5 N/mm) and preferably in the
range of 0.97 lb./in (0.17 N/mm) to 2.0 lb./in (0.35 N/mm) The
spring mechanism may be a mechanical spring or alternatively a gas
reservoir or elastomeric component to provide spring-like function.
The distal end of the tubular sleeve 47 may incorporate rubber,
elastomeric or deformable materials 49 to conform to the tissue
surface and aid the sealing effect and reduce the required sealing
area.
[0049] Alternatively, (FIG. 11) the sealing element may be a
separate component 50 that is placed on the eye and the device used
to penetrate the seal and underlying conjunctiva and sclera. The
separate component may be a soft polymer, rubber or elastomer of a
thickness to provide the appropriate main shaft length through the
conjunctiva and sclera to reach the target suprachoroidal or
sub-retinal space. The separate component may have a target region
51 of decreased thickness sized to fit the outer dimensions of the
device when the device is placed on the component to aid location
and stabilization of the device when placing the device on the eye,
penetrating the seal, and penetrating the overlying conjunctiva and
sclera. The separate component may also be of the appropriate
thickness to trigger release of the guard fluid or gas once the
distal lumen of the main shaft has entered the seal. Mechanical
features of the separate component such as a flange, sleeve or rod
extending toward the device as it is placed may trigger release of
the guard fluid or gas. The device may incorporate a stop 52, sized
to fit within the target region 51 of the sealing element which
controls the depth of entry of the distal tip of the device.
[0050] The device may also comprise indicators to show when the
guard has been deployed to protect the underlying choroid and
retina, and that a pathway to the suprachoroidal space or
sub-retinal space has been established. An indicator may comprise a
depth indicator of the mechanical guard or a volume or flow
indicator of the reservoir. An indicator may also be coupled to a
sensor to initiate a visual or audible signal to the user to limit
penetration with the device and indicate that the eye is ready for
injection of materials to the suprachoroidal or sub-retinal
space.
[0051] Referring to FIG. 12 the materials for injection into the
suprachoroidal space 32 or sub-retinal space 33 may comprise an
implant, a drug solution, drug suspension, or drug containing
material such as a gel or solid implant, gene therapy agents, stem
cells or cell therapy agents. In addition, the device may comprise
apparatus to extend a flexible tubular element within the
suprachoroidal space or sub-retinal space after deployment of the
guard, toward the posterior end of the eye to extend the distal
lumen and administer materials to a location closer to the
posterior region of the eye. The flexible tubular element is
preferred to have a rounded atraumatic distal end to minimize
trauma to the choroid or retina.
[0052] In another embodiment (FIG. 13), the device may comprise a
distal end and a proximal end in communication with each other as
previously described in conjunction with an outer sleeve that is
implanted into the sclera. The body of the device may be in the
form of a solid member or hollow tubular member 34 with a sharp tip
35. The device may incorporate a mechanical or fluidic guard as
previously described to displace the choroid for access to the
suprachoroidal space or to displace the retina for access to the
subretinal space. The device further comprises a thin walled sleeve
36 slideably disposed about the outer diameter of the body of the
device. The sleeve is advanced into the tissues as the device is
placed. The sleeve 36 remains behind when the device is removed
from the eye. As shown in FIG. 14, sleeve 36 functions as an access
port or introducer, in communication from the outside of the eye to
the suprachoroidal space 32 or sub-retinal space, for the
introduction of other devices such as needles, cannulae or
catheters into the space during surgery. The sleeve is typically
sized at about 0.0045 inch (0.11 mm) to 0.0355 inch (0.90 mm) outer
diameter with a wall thickness in the range of about 0.0005 inch
(0.12 mm) to 0.002 inch (0.5 mm) and a length in the range of about
0.60 inch (1.5 mm) to 0.195 inch (5 mm) The sleeve may also have an
enlarged diameter or flange at the proximal end to secure the
proximal end at the surface of the eye. The sleeve may comprise
metals such as nitinol, stainless steel, tungsten or polymers such
as polyimide, nylon, polyamide, PEEK, or polycarbonate.
[0053] The device may further comprise a feature to limit the depth
of penetration of the distal tip. This feature may comprise a
mechanical stop or flange disposed about the outer diameter of the
device body which limits travel by the stop encountering the
surface of the eye. The stop may be in the form of a flat surface
which may be disposed perpendicularly to the body of the device or
may be disposed at an angle to the body such that the angle
approximates the angle of the surface of the globe in relation to
the angle of entry by the device itself. The stop configurations
may be incorporated into the mechanism used to guard the device,
such as the outer tubular member previously described. The stop may
be adjustable to allow the user to tailor the use of the device to
different tissue thicknesses, for example in different regions of
the eye.
[0054] In many embodiments, as shown in the top view, FIG. 15, the
main shaft 12 with a pointed or beveled distal end 13 will have the
appropriate exposed length to access the target site. In the case
of access to suprachoroidal space, the length is preferred to be
sufficient to expose at least the most distal portion of the lumen
to the suprachoroidal space when the device is placed through the
conjunctiva and sclera to allow the guard to enter the space and
displace the underlying choroid. From anatomic considerations based
upon minimum combined tissue thickness of the conjunctiva and
sclera of 0.015 inch (0.38 mm), this length to the distal end of
the lumen is at minimum 0.025 inch (0.65 mm) In the case of access
to the sub-retinal space, the main shaft length is preferred to
have a length to expose the most distal portion of the lumen to the
sub-retinal space when the device is placed through the
conjunctiva, sclera and choroid. From anatomic considerations based
upon the average combined tissue thickness of conjunctiva, sclera
and choroid of 0.023 inch (0.58 mm), this length to the distal end
of the lumen is at minimum 0.023 inch (0.58 mm) To minimize damage
to the underlying tissue distal to the desired target space, the
main shaft length is preferred to be no more than the thickness of
the proximal tissue overlying the target space plus the amount of
tissue displacement of the underlying tissue due to the guarding
element. For access to the suprachoroidal space, this maximum
length is approximately 0.108 inch (2.75 mm) For access to the
sub-retinal space, this maximum length is approximately 0.118 inch
(3.00 mm) When the device is used in conjunction with a sealing
element, the preferred lengths are the effective lengths of the
main shaft with respect to the distal edge 53 of the lumen and
distal, beveled tip 54 to the distal, tissue contacting surface of
the seal 55. In addition to the anatomical dimensions, the
preferred functional lengths of the main shaft should also account
for the mechanical characteristics of the tissues to be penetrated
to account for tissue deformation during use of the device.
[0055] The following Examples are provided for the purpose of
illustrating particular devices and methods according to the
invention. These Examples are not intended to limit the scope of
the invention in any manner.
EXAMPLES
Example 1
[0056] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of a needle as the main shaft and a
spring loaded guard element. The needle element was comprised of a
27 gauge (0.4 mm).times.0.5 inch (12.7 mm) short bevel hypodermic
needle (Monoject, Covidien Inc) as the main shaft. The needle tip
bevel angle was 18.degree., and the proximal end was a standard
Luer lock connector. The spring loaded guard element was comprised
of a stainless steel wire 0.007 inch (0.18 mm) diameter sized to
fit slideably within the lumen of the needle element main shaft and
of a length so that the distal tip of the wire extended beyond the
distal needle tip by 0.004 inch (0.1 mm) The tip of the wire was
rounded so as not to have any sharp edges. The wire was welded into
a larger stainless steel tube, sized to slideably fit inside a
compression spring. A spring perch was welded to the distal end of
said tube. A spring with an inner diameter of 0.049 inch (1.25 mm)
and a spring rate of 0.7 lb./in (0.12 N/mm) was placed over said
tube. A second outer tube, sized to fit slideably about the spring
tube and with an outer diameter larger than the spring outer
diameter was placed about the spring tube, to act as a proximal
stop for the spring. The wire was inserted into the lumen of the
needle element. A Touhy-Borst Luer connector was attached to the
needle Luer connector, and then tightened about the outer tube to
hold it in place. This spring assembly allowed the wire to move
rearward inside the needle.
[0057] A human cadaver eye was used for the experiment. The guard
wire tip was placed against the tissue surface and the device
advanced slowly into the tissues. The guard tip was seen to retract
against the spring pressure, allowing the needle tip to enter the
tissues. When the needle had been inserted approximately 0.6 inch
(1.5 mm) the advancement was stopped. Using a high resolution
optical coherence tomography (OCT) imaging system, the device
placement was imaged. The needle tip could be clearly seen in the
suprachoroidal space with the guard tip extending beyond the needle
tip and displacing the choroid
Example 2
[0058] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of a stainless steel tubular main
shaft, 0.79 inches (20 mm) long and 0.016 inches (0.4 mm) outer
diameter and 0.008 inches (0.2 mm) inner diameter with a sharp
12.degree. beveled tip. The main shaft was bonded proximally into a
plastic female Luer connector. A mechanical guard element comprised
of a distal thin walled polyimide tube with an inner diameter
0.0165 inches (0.42 mm) and outer diameter of 0.0175 inches (0.45
mm) was bonded to a proximal stop 0.04 inches (1.0 mm) in diameter.
The distal end of the polyimide tubing was beveled to allow for
entry into the tissues. The guard member was loaded onto the main
shaft with a stainless steel spring of 0.017 inches (0.43 mm) inner
diameter with the spring wire diameter of 0.005 inches (0.13 mm)
between the guard and the plastic hub, disposed about the main
shaft. The device was tested using a human cadaver eye. The tip of
the device was inserted into the sclera and advanced forward. The
mechanical guard was pushed rearward, allowing the sharp main shaft
tip to enter the scleral tissues. With continued advancement, the
guard element was also advanced into the sclera. When the distal
tip of the main shaft entered the suprachoroidal space, the spring
force advanced the guard element ahead of the main shaft tip,
displacing the choroid. Optical Coherence Tomography (OCT) imaging
confirmed the guard element tip location within the suprachoroidal
space.
Example 3
[0059] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of a metal main shaft 0.79 inches
(20 mm) long and 0.016 inches (0.41 mm) outer diameter and 0.008
inches (0.2 mm) inner diameter with a sharp beveled tip. The main
shaft was sealed at the proximal end and a side hole was made
approximately 0.197 inches (5 mm) from the end. The device distal
tip was angled to 30.degree. and 0.059 inches (1.5 mm) length. The
device featured a spring retractable metal sleeve disposed about
the main shaft distal tip and that acted as a mechanism to trigger
the infusion of gas into the suprachoroidal space when it
retracted. The spring proximal end was attached to a metal sleeve
that added structural support of the main shaft and Luer
attachment. A Luer connector with a polymer septum was secured to
the proximal end of the main shaft such that the main shaft
penetrated the septum with the side hole distal to the septum. A
check valve assembly was attached to the Luer connector to serve as
a gas filled reservoir providing a means of infusing gas into
suprachoroidal space to displace the choroid. The device was tested
using a human cadaver eye. The device angled tip was inserted into
the sclera near the pars plana and advanced until the angled tip
was positioned in the suprachoroidal space. Upon contact with the
scleral surface, the distal metal sleeve was pushed rearward until
the spring force overcame the frictional force of the main shaft in
the septum, which drove the proximal end of the main shaft through
the septum positioning the side hole above the septum. Gas within
the chamber was released through the main shaft, out the tip, and
into the suprachoroidal space. Optical Coherence Tomography (OCT)
imaging confirmed the tip location within the suprachoroidal space
and release of the fluidic air guard, displacing the choroid to
prevent contact of the choroid with the tip.
Example 4
[0060] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device main shaft was comprised of a 0.016 inches (0.41
mm) outer diameter and 0.008 inches (0.2 mm) inner diameter and
0.984 inches (25 mm) long injection needle with sharp bevel
straight tip and proximal Luer connector. Additional design
features included a metal proximal and distal outer housing
assembly, 0.028 inch (0.7 mm) diameter by 0.472 inches (12 mm) long
segments connected by a 0.197 inches (5 mm) long coil spring. The
distal outer housing segment provided a spring retractable
protective sleeve and insertion depth stop at the main shaft distal
tip. The proximal outer housing segment was attached to the main
shaft for improved device rigidity. The proximal main shaft open
end was inserted into a polymer septum of a pressurized fluid
filled reservoir. The device was tested using a human cadaver eye.
Upon inserting the device distal tip through the sclera and into
the suprachoroidal space, the proximal main shaft moved backward
axially, pierced through the septum and into the fluid reservoir.
The reservoir content was then released into the open end of the
proximal main shaft and discharged out the distal tip and into the
suprachoroidal space. The resulting choroid displacement to prevent
contact of the distal tip with the choroid was monitored and
confirmed in real time with ultrasound imaging.
Example 5
[0061] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of a metal main shaft 0.79 inches
(20 mm) long and 0.016 inches (0.41 mm) outer diameter and 0.008
inches (0.2 mm) inner diameter with a sharp beveled tip. The main
shaft was sealed at the proximal end and a side hole was made
approximately 0.197 inches (5 mm) from the end. A Luer connector
with a polymer septum was secured to the proximal end of the main
shaft such that the main shaft penetrated through, with the side
hole distal to the septum. A check valve assembly was attached to
the Luer connector providing for a Tillable gas reservoir of
approximately 100 microliters volume. A metal sleeve with an inner
diameter of 0.020 inches (0.51 mm) and an outer diameter of 0.028
inch (0.71 mm) was disposed about the main shaft and attached to it
near the proximal end. The sleeve acted as a mechanism to trigger
the release of the gas filled reservoir into the suprachoroidal
space when forced rearward, translating the side port to the
reservoir side of the septum. An access port element 0.0065 inch
(0.17 mm) inner diameter and 0.0005 inch (0.012 mm) wall thickness
comprised of polyimide was disposed about the outside of the main
shaft and inserted under the metal sleeve. The device was tested
using a human cadaver eye. The device tip was inserted into the
sclera near the pars plana and advanced until the tip entered the
suprachoroidal space and the sleeve triggered the release of the
reservoir, injecting gas to displace the choroid. The port element
was then advanced forward into the suprachoroidal space. Optical
Coherence Tomography (OCT) imaging confirmed the distal end of the
port location within the suprachoroidal space and a fluid injection
was made through the port, while confirming inflation of the
suprachoroidal space on imaging.
Example 6
[0062] Devices fabricated according to Example 5 were tested to
determine the delivered pressure of a gaseous fluidic guard based
upon the amount of gas charged into the reservoir and to determine
the amount of choroidal displacement achieved due to the gas charge
in the reservoir. A diaphragm pressure transducer (PX26-100GV,
Omega Engineering) was modified to place a Luer injection port into
the transducer port, minimizing the dead volume of the transducer.
The transducer was connected to a digital readout (DP-41S, Omega
Engineering) and then calibrated to read out in mm Hg. The main
shaft needle tip of a device under test was inserted into the
injection port of the pressure transducer. The check valve was
removed and the Luer connector advanced to open the internal valve
mechanism and equalize the system pressure. The Luer connector was
then pulled back, closing the internal valve and the check valve
was re-installed. A 1 cc syringe was filled with a volume of air,
attached to the check valve Luer connector of the device and then
expelled to charge the reservoir. The device was advanced to open
the internal valve and the gauge pressure of the delivered gas was
read from the digital readout. Syringe volumes of 0.1 cc to 0.7 cc
were tested. However the actual fill volume of the reservoir was
less than the syringe volume. Due to the fixed volume of the
reservoir and the limited ability of a manual syringe to compress
the gas, a small amount of gas refluxed into the syringe as
evidenced by the rebound of the syringe plunger after full
depression of the plunger.
[0063] Additional devices were tested in-vitro using both human and
porcine cadaver eyes, and in-vitro using a live porcine animal
model. A 1 cc syringe was used to load the device reservoirs with
0.2, 0.4 or 0.6 cc of air. The devices were advanced into the eyes,
activating the internal valve and releasing the reservoir contents,
and the resultant choroidal displacement was measured using high
frequency ultrasound imaging. The table below shows the
experimental results.
TABLE-US-00001 TABLE 1 Average Average Choroid Choroid Average
Displace- Displace- Average Syringe Gauge ment (mm) - ment (mm) -
Choroid Charge Pressure Human Porcine Displacement Volume (mm Hg)
Cadaver Cadaver (mm) - Live (cc) Delivered Eyes Eyes Porcine Eyes
0.1 4.7 -- -- -- 0.2 8.3 0.63 0.75 0.34 0.3 11.6 -- -- -- 0.4 14.8
1.01 0.86 0.61 0.5 18.1 -- -- -- 0.6 21.3 1.10 1.00 0.76 0.7 24.4
-- --
Example 7
[0064] A device fabricated according to Example 5 was tested for
its ability to deliver a therapeutic agent to the suprachoroidal
space. Porcine cadaver eyes were used in the experiment. The device
reservoir was charged with 0.5 cc of air as the fluidic guard
material. A syringe containing 0.25 cc of triamcinolone acetonide
(TA), a corticosteroid particulate suspension (Kenalog 40, Bristol
Meyers Squib), was attached to the proximal Luer connector of the
device. The device was placed against the sclera of the cadaver eye
and advanced until the distal tip entered the suprachoroidal space
and discharged the reservoir gas, displacing the choroid away from
the tip. After entering the space, the syringe plunger was
depressed, injecting the TA suspension. High frequency ultrasound
imaging confirmed that the suprachoroidal space had been opened and
that TA particles were visible in the space. A perfusion system was
set-up consisting of a reservoir of phosphate buffered saline (PBS)
on a variable height platform. Tubing was attached to a port at the
bottom edge of the reservoir, leading to a shut-off valve and a
small tube with a Luer connector at the end. A 30 gauge (0.3 mm)
hypodermic needle was attached to the reservoir Luer connector. The
reservoir was elevated to provide 0.29 PSI (15 mm Hg) pressure. The
30 gauge needle was inserted through the cornea and into the
anterior chamber to provide perfusion to the cadaver eye. The eye
was allowed to perfuse for 6 hours at constant pressure. After the
perfusion, the sclera of the eye over the injection site was
dissected and removed. Examination under a light microscope showed
the depot location of the TA particles on the choroid surface
around the injection site. Also noted was a stream of particles
extending approximately 0.55 inches (14 mm) posterior from the
injection site, indicating a flow directed movement of the
injectate towards the posterior pole of the eye.
Example 8
[0065] In another test, a device fabricated according to Example 5
was tested in the manner of Example 5, however the device reservoir
was charged with the suspension steroid instead of air. A syringe
with additional injectate was attached to the device. The device
was advanced into the tissues and the reservoir fluid contents were
discharged when the suprachoroidal space was reached, displacing
the choroid and allowing for injection of the remaining fluid in
the syringe into the suprachoroidal space. The injection location
and tissue displacement was confirmed by ultrasound imaging.
Example 9
[0066] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The shafts and housings of the device were fabricated from
304 stainless steel hypodermic tubing. The device was comprised of
a distal shaft of 0.016 inches (0.4 mm) outer diameter and 0.008
inches (0.2 mm) inner diameter by 0.75 inches (19 mm) long. The
distal shaft had a standard hypodermic beveled tip with a main
bevel angle of 12.degree.. A shaft extension of 0.017 inches (0.43
mm) inner diameter and 0.025 inches (0.64 mm) outer diameter and
0.24 inches (6 mm) long was welded to the back of the distal shaft.
A proximal shaft, the same diameter as the distal shaft and 0.42
inches (10.8 mm) long was cut and one end was welded shut. A side
hole was ground through the wall 0.005 inches (0.13 mm) from the
welded end. The distal end of the proximal shaft was slid inside
the shaft extension on the distal shaft. A piece of 50 durometer
silicone tubing 0.015 inches (0.38 mm) inner diameter by 0.027
inches (0.69 mm) by 0.2 inches (5 mm) long was placed over the
junction between the proximal and distal shafts to seal the gap. An
outer housing of 0.033 inches (0.84 mm) inner diameter by 0.046
inches (1.17 mm) outer diameter by 0.71 inches (18 mm) long was
cut. Starting at 0.16 inches (4 mm) from the distal end of the
outer housing and extending 0.5 inches (13 mm) long, one half of
the outer housing was ground off leaving a half circle of tubing.
An extension tube of 0.02 inches (0.51 mm) inner diameter by 0.032
inches (0.81 mm) outer diameter by 0.55 inches (14 mm) long was
welded into the distal end of the outer housing, so as to act as
the tissue contact portion of the moving assembly. The
distal/proximal shaft assembly was placed inside the outer housing
and a cross beam was welded to the distal shaft. The cross beam was
adhesively bonded to a polycarbonate Luer connector. Inside the
proximal end of the Luer connector, a solid disk of 50 durometer
silicone rubber was inserted as a septum, with the tip of the
proximal shaft just penetrating the septum so that the side hole
was below the septum. A Luer check valve was attached to the Luer
connector creating a sealed reservoir that could be filled from the
Luer connector on the check valve.
[0067] The device was tested using a human cadaver eye. The
reservoir was filled with air from a syringe. The device was placed
against the tissue surface and advanced. As the outer housing
assembly translated rearward, the side hole in the proximal shaft
was translated to the reservoir side of the septum. The gas was
released to displace the choroid and an injection of a suspension
steroid (Kenalog 40, Bristol Meyers Squib) was made into the
suprachoroidal space. The injection location was confirmed with
ultrasound imaging.
Example 10
[0068] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of a commercial 27 ga (0.4 mm) by
0.5 inch (12.7 mm) short bevel hypodermic needle (Monoject 27
g.times.1/2 needle, Covidien Inc.) with a bevel main angle of
18.degree. as the main shaft. A sliding seal assembly was
fabricated as follows. Two pieces of polycarbonate tubing of 0.018
inches (0.46 mm) inner diameter by 0.060 inches (1.52 mm) outer
diameter were cut, a long piece at 0.37 inches (9.4 mm) and a short
piece at 0.08 inches (2.0 mm) long. The proximal end of the longer
piece was counter-bored at 0.028 inches (0.71 mm) diameter by 0.05
inches (1.3 mm) deep. A piece of 50 durometer silicone tubing 0.015
inches (0.38 mm) inner diameter by 0.027 inches (0.69 mm) outer
diameter by 0.04 inches (1.0 mm) long was cut and inserted into the
counter-bore in the long tube as an inner seal. The short piece of
polycarbonate tubing was then adhesively bonded to the long tube
over the counter-bore to cap the inner seal in place. A piece of 50
durometer silicone tubing of 0.025 inches (0.64 mm) inner diameter
by 0.047 inches (1.2 mm) outer diameter was placed over the distal
end of the polycarbonate assembly to form an outer seal. The
silicone tubing was placed such that the distal edge extended
beyond the end of the polycarbonate tubing to serve as a seal
against the tissue surface. A spring with a spring constant of 0.97
lb./in (0.17 N/mm) was placed over the hypodermic needle and the
sealing assembly was slid over the needle.
[0069] The device was tested using human cadaver eyes. 1 cc syringe
was filled with 0.1 cc of a suspension steroid (Kenalog 40, Bristol
Meyers Squib) and the syringe attached to the device. The tip of
the device was placed in contact with the tissues and light
pressure was placed on the syringe plunger, effectively
pressurizing the fluid pathway. The device was advanced into the
tissues, keeping the sealing assembly in contact with the surface
and maintaining pressure on the syringe plunger. When the needle
tip advanced through the sclera a sufficient distance, the fluid
was able to be injected, displacing the choroid and injecting the
fluid into the suprachoroidal space. The injection location was
confirmed with ultrasound imaging.
Example 11
[0070] A device according to one embodiment of the invention was
fabricated and tested for its ability to successfully penetrate the
sclera and displace the choroid for access to the suprachoroidal
space. The device was comprised of an elastomeric tissue surface
seal and a needle assembly as the main shaft with an integral depth
stop. Two different models of the tissue surface seal were
fabricated. The surface seal was comprised of 50A durometer
silicone rubber. Disc shaped base elements, 0.06 inch (1.6 mm) in
thickness were fabricated, either 0.17 inch (4.4 mm) or 0.26 inch
(6.6 mm) in diameter. Annular shaped seal elements of the same
thickness were fabricated with an outer diameter of 0.17 inch (4.4
mm) and an inner diameter of 0.06 inch (1.52 mm). An annular
element was adhesively bonded centrally to a base element, using
room-temperature vulcanization (RTV) silicone adhesive. A main
shaft needle assembly was fabricated comprising a 27 ga (0.4
mm).times.0.5 inch (12.7 mm) short bevel hypodermic needle
(Monoject, Covidien Inc.). A short length of polycarbonate tubing
0.018 inches (0.46 mm) inner diameter by 0.06 inches (1.52 mm)
outer diameter was placed over the needle shaft as a depth stop.
The tubing was cut to a length so that the exposed needle length
was 0.13 inch (3.35 mm) In combination with the thickness of the
tissue seal base, this length would provide for a needle length
extending beyond the base element, to enter the tissues, of 0.07
inch (1.75 mm) The outer diameter of depth stop was sized to fit
snugly and seal within the inner diameter of the annular seal
element.
[0071] A human cadaver eye was prepared. The tissue surface at the
pars plana was carefully dried and a tissue seal assembly was
placed in contact with the surface and pressed down to effect a
seal. A 1 cc syringe was filled with 0.1 cc of triamcinolone
acetonide steroid suspension (Kenalog 40, Bristol Meyers Squib) and
attached to the needle assembly. The needle tip was inserted into
the center of the base element and advanced so that the depth stop
entered the inner diameter of the annular element, scaling the
fluid pathway. The needle advance was continued along with light
pressure on the syringe plunger. When the depth stop reached the
based element, and with the needle inserted to full depth, the
injection was made. Ultrasound imaging confirmed the injectate in
the suprachoroidal space. Both tissue seal devices, having
different base element diameters, were successful.
Example 12
[0072] An experiment was performed to determine the range of
lengths of the main shaft which would allow for injection into the
suprachoroidal space in an eye. An adjustable stop was fabricated,
sized to go over a 27 gauge (0.4 mm) hypodermic needle used as the
main shaft. The distal end of the stop was 1.5 mm (0.06 inch) in
diameter and the stop could be fixed in place so as to be able to
have a set amount of needle tip extending beyond it. Two different
needle bevels were tested. A standard hypodermic needle, with a
nominal main bevel angle of 12 degrees (Precision Glide--27
ga.times.1/2 inch, Becton-Dickenson) and a short bevel needle, with
a nominal main bevel angle of 18 degrees (Monoject 250--27
ga.times.1/2 inch, Covidien) were used in the tests.
[0073] Human cadaver eyes were procured and ultrasound imaging was
used to determine the average tissue thickness. The average surface
tissue (scleral) thickness was 0.028 inch (0.70 mm) and the average
full tissue thickness (sclera and choroid) was 0.045 inch (0.1.15
mm) Triamcinolone acetonide (Kenelog-40, Bristol Meyers Squib), a
suspension steroid, was used as the injectate as the injected
particles are clearly visible using ultrasound imaging. A 1 cc
syringe was filled with 0.1 cc of triamcinolone for each test and
attached to the test needle.
[0074] For each test, the adjustable stop was set to a preset
needle length, as measured with a digital caliper. The needle tip
was inserted into the tissue at the pars plana and with the
adjustable stop fully pressed against the tissue surface and an
injection of the triamcinolone was attempted. The injection was
then evaluated using the ultrasound system to determine whether the
injection was A) unsuccessful, i.e. no injection, too shallow, B)
successful in injecting into the suprachoroidal space, or C)
injected into the vitreous cavity, i.e. too deep. The following
table presents the test results along with the distance between the
distal end of the adjustable stop and the distal edge of the needle
tip lumen. The results indicate a main shaft or needle length
greater than 0.05 inch (1.25 mm) and less than 0.12 inch (3.00 mm)
provide the best results for injection into the suprachoroidal
space.
TABLE-US-00002 TABLE 2 Standard Bevel Short Bevel Needle, Standard
Needle, Distal Stop Bevel Distal Stop Short to Needle to Bevel
Needle Distal Edge Result Distal Edge Needle Length of Lumen (A, B,
of Lumen Result (A, (mm) (in/mm) C) (in/mm) B, C) 0.25 0.002/0.06 A
0.003/0.08 A 0.50 0.012/0.31 A 0.013/0.33 A 0.75 0.022/0.56 A
0.023/0.58 A 1.00 0.032/0.81 A 0.033/0.83 A 1.25 0.042/1.06 B
0.043/1.08 B 1.50 0.052/1.31 B 0.052/1.33 B 1.75 0.061/1.56 B
0.062/1.58 B 2.00 0.071/1.81 B 0.072/1.83 B 2.25 0.081/2.06 B
0.082/2.08 B 2.50 0.091/2.31 B 0.092/2.33 C 2.75 0.101/2.56 B
0.102/2.58 C 3.00 0.111/2.81 C 0.111/2.83 C
Example 13
[0075] The device of Example 5 was filled with 0.3 ml of air to act
as a fluidic guard. The device was used to access the
suprachoroidal space of eyes in anesthetized pigs at the pars plana
region of the eye. Once the gas was injected into the
suprachoroidal space, the device was used to inject 0.1 ml (4 mg)
of triamcinolone acetonide suspension (Kenalog-40, Bristol Meyers
Squib). Twelve eyes were injected and three each harvested at 1, 7,
14 and 30 days post injection. The eyes were dissected and 6 mm
punches taken from the vitreous, retina, choroid and sclera at four
quadrants of the eye and also the posterior retina. The level of
drug in the tissues was assayed by solvent extraction of the
tissues and quantitation by reverse phase HPLC. The results shown
in FIG. 16 demonstrated sustained availability of triamcinolone
acetonide in all regions of the eye, including the posterior retina
through 30 days with the highest level of drug in the choroid and
decreasing levels of drug in the sclera, retina and vitreous.
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