WO2003092564A1

WO2003092564A1 - Device for delivery of biologically active agents

Info

Publication number: WO2003092564A1
Application number: PCT/GB2003/001840
Authority: WO
Inventors: Bruce Duncan Samuel Allan
Original assignee: Moorfields Eye Hospital Nhs Trust; Institute Of Ophthalmology
Priority date: 2002-05-01
Filing date: 2003-05-01
Publication date: 2003-11-13
Also published as: AU2003224316A1; AU2003224316A8

Abstract

This invention relates to treatment of the eye and provides an implantable, intraocular, sustained release device wherein the device comprises: a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverses the eye wall wherein the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens; and b) a member, attached to the body portion, which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and is adapted so that the distal end extends into a humour of the eye.

Description

DEVICE FOR DELIVERY OF BIOLOGICALLY ACTIVE AGENTS

Technical Field

The present invention relates to treatment of eye diseases. Poor penetration into the eye of biologically active agents administered systemically, topically or periocularly limits the effectiveness of such treatments. For example highly effective clearance mechanisms limit the usefulness of topically administered actives. Many diseases affecting the eye require prolonged treatment . Therefore, treatment via systemic administration of biologically active agents can lead to undesirable side effects. Intraocular administration of actives substantially eliminates this problem.

Summary of Prior Art

Injection into the eye of biologically active agents removes side effects observed with systemic administration. It is necessary, however, to consider the retinal toxicity of the active. In addition, rapid elimination of the injected drug is observed.

Injection of encapsulated actives, for example in liposomes, microparticles and nanopartides, prolongs the residence of the drug in the eye and reduces the intraocular toxicity to the retina. Encapsulated drugs, however, have the disadvantage that once injected into the eye it is not possible to remove the particles should immediate cessation of administration of the active be required. More recent advances have focussed on the administration of biologically active agents by implants or depot devices. The Vitrasert (trade mark) device is a commercially available, sustained release, intraocular device approved for use in patients suffering from cytomegalovirus retinitis. The device consists of a pellet of ganciclovir coated with ethylene vinyl acetate (EVA) and polyvinyl alcohol (PVA) to give the sustained release effect. The device is located within the vitreous humour of the eye and is anchored in place with sutures passing through the the eye wall. Exhausted devices have to be removed surgically, by creating further, sometimes larger, incisions across the eye wall, which is an important limitation. Some studies have been carried out on eyes in which an exhausted device is removed and replaced. Martin et a.1 (1997) reported that complications after the second implant procedure include transient vitreous hemorrhage, postoperative inflammation and retinal detachment. Complications were worse after the third implant and included dense vitreous hemorrhage in 75% of eyes tested. A later study by MacCumber et al (1999) reported that implant exchange can be difficult to perform in some cases due to shifting of the implant and scar formation and there is a risk of increased intraocular bleeding and intraocular dislocation during manipulation of the implant. An alternative approach is multiple implants, but multiple large scale sclerotomies cause weakening of the eye wall and multiple implants can reduce vision. Koch et al (1999) has reported that the Vitrasert (trade mark) implant can become completely covered by a fibrous membrane . This would also lead to further complications when removing the implants. Neurotech have developed an encapsulated cell device which can be used for the treatment of eye diseases . Encapsulated cell implants consist of cells encapsulated within semipermeable polymer membranes and supportive matrices. The encapsulated cells are genetically engineered to produce the desired biologically active agents that target specific diseases or conditions. The encapsulated intravitreal device is implanted into the vitreous humour of the eye and the cells derive their nourishment from the surrounding milieu. Actives produced by the cells are able to pass through the membrane into the vitreous humour. The implant is held in position by suturing to the eye wall in a similar fashion to the Vitrasert (trade mark) device. It is therefore expected that the same limitations experienced by the Vitrasert (trade mark) device, caused by the need for repeated incisions across the eye wall to remove or replace devices, will also be observed with the encapsulated cell device.

Description of the Invention

According to this invention, an implantable, intraocular, sustained release device is provided wherein the device comprises : a) a body portion that is positioned in a slit incision in an eye wall and traverses the eye wall wherein the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens and b) a member, attached to the body portion, which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and is adapted so that the distal end extends into a humour of the eye .

In one form of the device a member is an integral part of the device and is permanently attached to the body portion. In an alternative form a member is removably attached to the body portion and can be removed and replaced with another member.

Advantages of the present invention are that a device is provided which enables the sustained release of a biologically active agent within the eye and the device traverses the eye wall so it is able to be easily located and removed, replaced or replenished without creating further incisions in the eye wall. This significantly reduces trauma to the eye wall .

The inventor has also identified the need for a device which traverses the eye wall to be formed in such a way that it substantially eliminates any leakage of intraocular fluid around the body of the device. Therefore another advantage of the present invention is that the body portion of the device has the necessary shape features and is formed of suitable materials so as to prevent such leakage . A sustained release device of this invention may comprise more than one member attached to the body portion and extending into a humour of the eye from which a biologically active agent is released over a sustained period. In this specification a biologically active agent is any molecule which causes a change in the eye . Such biologically active agents include drugs, therapeutic agents, peptides, proteins, glycosamino glycans, prostaglandins , peptidoglycans . Sustained release means release from the device into a humour of the eye to achieve a sustained therapeutically useful concentration within the eye over a period of more than 1 day, preferably more than 7 days and more preferably more than 30 days. A member from which a biologically active agent is released may comprise a biologically active agent, for example, a drug pellet surrounded by a polymer membrane; such a drug may be supported by a matrix. Alternatively a member may comprise a means of producing a biologically active agent, preferably immobilized or encapsulated cells capable of releasing a specific biologically active agent, examples include neuroprotective factors eg CTNF for prevention of macular degeneration, vascular growth inhibitors eg a VEGF receptor blocker to prevent diabetic retinopathy, a prostagandin to lower intraocular pressure eg PG2E for glaucoma.

The polymer surrounding a member must enable a biologically active agent to diffuse out of the member over a sustained period: provide a biologically active agent releasing surface. This may be formed from any polymer which allows the necessary molecules to move out of (or into) a member. Examples include synthetic polymers and copolymers which have reproducible characteristics such as poly-L-lysine. A member may comprise a matrix to support the biologically active agent or cells which may be formed from hydrogels such as polysaccharide gels (eg alginates, chitoson, agar etc) proteins (eg collagens and gelatin) and synthetic polymers (eg polyvinyl capralact m, polyacrylamides and methacrylates) .

A sustained release device according to this invention is preferably held in position by a retaining flange attached to the body portion at the outer side of an eye wall. The retaining flange prevents movement of a device further into the eye .

The retaining flange may either rest on the outside the eye wall or the device may be counter sunk such that the outer edge of the flange is flush with the outer edge of the eye wall.

A longest dimension of a retaining flange may be at right angles to the axis of the body portion. It is envisioned that this will be the case when the implantable, intraocular, sustained release device is intended for use in the posterior chamber of the eye for delivery of a biologically active agent to the vitreous humour. Alternatively a longest dimension of a retaining flange may be positioned at an angle other than at right angles to the axis of the body portion. It is envisioned that this will be the case when the implantable, intraocular, sustained release device is intended for use in the anterior chamber of the eye for delivery of a biologically active agent to the aqueous humour.

Optionally a sustained release device according to this invention may also be held in position by suturing to the eye wall.

Preferably a sustained release device according to this invention has a tapered interior end, meaning the end which is positioned further inside the eye, and the tapered end may sit inside a humour of the eye. As stated above the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens. Preferably the ratio of the longest diameter to the shortest diameter being in the range (1.5 to 2.5):1. Also preferably the cross section is symmetrical about both the longest and shortest diameters . It is envisaged that the longest diameter is in the range 0.8 to 1.16mm and preferably the shortest diameter is in the range 0.29 to 0.6mm. It is also possible for the device of this invention to be a nano engineered device meaning a device of the same type but with much smaller dimensions. Such a device would have a longest diameter of up to 0.8 mm and a shortest diameter of up to 0.29 mm. The device is inserted into an incision formed as a slit in the eye wall with the greatest diameter of the cross-section of the body wall equal to and aligned with the slit. The external profile of the device ensures that the tissues at the incision bear directly against the external wall of the implant around substantially the entire circumference of the device. This minimises leakage of intraocular fluid through the incision around the external wall of the device.

To provide a further reduction in the flow of fluid through the incision around the outside of the device, it is preferred for the body portion, along at least part of its length, to have an external layer at the external surface which is resilient and has a relatively low hardness . The use of a soft material at the surface of the body portion allows for the surface to deform to conform to the tissue at the incision, thereby minimising any gap between the body portion and the tissue.

In this invention the hardness of the respective materials refers to the hardness under conditions of use, in terms of surrounding/imbued liquid environment and temperature . Alternatively the body portion may be formed of a relatively soft material to allow local deformation at the external surface. Additionally or alternatively the outer surface of the body portion of the device could be formed of a gel material which swells after insertion of the device in an incision, the extent of swelling being dependent upon the pressure exerted on the surface of the material by the internal surface of the slit incision. In general materials suitable for forming a body portion of a device are elastomeric in nature for example silicones or polyurethanes . In an alternative form when the body portion could be formed of a gel material, hydrogels are a suitable example.

Where materials to form a body portion are thermoplastic, they may be shaped by melt processing techniques. For non-thermoplastic materials, for instance hydrogels or other cross-linked materials, the device may be formed by polymerizing or cross-linking a liquid starting material in a mould. The bulk formed product may form the device itself or may form a precursor which is subjected to subsequent shaping steps such as lathe cutting, drilling etc. Silicone based devices and or cross-linked polyacrylates may be made by such moulding techniques . Polyurethanes may be made by melt blending techniques.

A first type of implantable, intraocular, sustained release device according to the present invention, in which a member (from which a biologically active agent is released over a sustained period) is an integral part of the device and permanently attached to the body portion, has a surface which is biocompatible and substantially bioinert . Such a device will not adhere to the eye wall and should not cause fibrous membranes to grow over the device. The resulting device is therefore easy to locate and remove from the eye when treatment is to cease or the device is exhausted. Suitable biocompatible and substantially bioinert materials include materials incorporating phosphorylcholine (PC) or polyethylene glycol (PEG) groups.

A second type of implantable, intraocular, sustained release device according to the present invention, in which a member (from which a biologically active agent is released over a sustained period) is removably attached to the body portion and can be removed and replaced with another member, is formed in such a way as to encourage bio-integration of the device. For example by having a body portion with a porous outer element or a surface which favours cell adhesion. Suitable materials which encourage bio-integration of the body portion include bioactive materials, materials incorporating or mimicking natural adhesion structures; and surface modified materials such as bioactive glasses, ceramics and composites . The body portion may also have barbs or ridges which assist in holding the device in place.

In the second type of the device preferably a member and a body portion have means for removably attaching the member to the body portion. Preferably the body portion has a lumen in which a proximal end of a member is received. It is envisaged that the combination of body portion lumen and surface of a proximal end of a member comprises a deformable section to hold a member in the body portion lumen. The proximal end is preferably held in the lumen by a deformable flange on the member which fits into a recess in the lumen wall. The distal end of the member is in contact with a humour.

In one embodiment of the second type of the device the lumen extends from the interior end of the body portion in contact with a humour of the eye, part of the way through the body portion of the device. A member is removed and inserted from the inside of the eye, for example using endoscope technology. This ensures that the tissues overlying the device do not need to be disturbed during removal and re-insertion of a member. As the lumen does not extend the entire length of the body portion there is no risk of leakage of intraocular fluid via the lumen of the device. To enable a member to be inserted from the inside of the eye, the member is sufficiently mechanically strong to withstand being pushed into the lumen of the body portion of the device. Preferably the mechanical strength is provided by a coating around or a matrix inside a member. The distal end of a member preferably has a mechanically stronger section which facilitates manipulation of the member. In an alternative embodiment of the second type of the device, the body portion of the device has a lumen which extends its entire length. A member is removed and inserted from the inside or outside of the eye. In this embodiment, there may be an additional mechanism to prevent leakage of intraocular fluid via the lumen of the body portion by relative deformation of either the member or body element to provide a seal. A member, however, may generally not need to be as mechanically strong as for the embodiment of the device described immediately above . This may be an advantage for members which release certain biologically active agents. It is preferable that a member for use in this embodiment has a mechanically strengthened proximal tip to facilitate manipulation of the member. In an embodiment of the second type of the device in which the exterior surface has low hardness and is soft enough to enable deformation of the material when placed in a slit incision in the eye wall, a lumen wall of the device is formed of a material of higher hardness . This enables the lumen to remain sufficiently open, despite imposition of an external force on the outer surface of the device, such that the lumen can receive a member.

Where the material of the external surface is of a different type to the relatively hard internal material through which the or each lumen is formed, a precursor for forming the relatively hard portion may be preformed, for instance by melt processing techniques or by polymerisation or cross-linking of liquid starting materials in a mould. The preformed hard portion may subsequently have the relatively soft outer layer formed onto it by coating it with a liquid precursor of the soft material, e.g. a solution of preformed polymer in a solvent or a polymerisable or cross-linking liquid which forms the soft material upon curing. The coating may take place in multiple stages to build up an adequate thickness for the surface layer to be sufficiently deformable in use. Alternatively the preformed hard portion may be placed in a mould with liquid precursor for the softer portion which is then polymerised or crosslinked in the mould in the presence of and around the preform. A melt processable softer material may be extruded onto a preformed harder component or, where both materials are melt processable they may be coextruded in the desired shape.

In this second type of device a body portion and members may be produced separately. One body portion implanted into an eye is preferably used with more than one member .

More than one member comprising a biologically active agent releasing surface for release of a biologically active agent over a sustained period and means for releasable attachment to a body portion may be used with a single body portion implanted in an eye wall. When a member is produced it may comprise a biologically active agent or a means of producing a biologically active agent such as cells capable of releasing a biologically active agent. The biologically active agent or cells may be supported by a matrix. This provides the advantage that the member is produced in a ready to use form.

Alternatively a member may be produced as a biologically active agent releasing surface and comprise space for later addition of a biologically active agent or immobilized or encapsulated cells. This provides the advantage that a medical practitioner can select a particular biologically active agent or cell line for use in a member.

An eye disease can be treated in a method using an implantable, intraocular, sustained release device comprising: a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverses the eye wall wherein the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens and b) a member, attached to the body portion, which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and is adapted so that the distal end extends into a humour of the eye .

In a method wherein a member is an integral part of the device and permanently attached to a body portion the processes by which a device can be implanted and removed after use require only one incision across the eye wall. In a method wherein a member is removably attached to the body portion and can be removed and replaced with another member the processes by which a device can be implanted and removed after use and a member can be replaced require only one incision across an eye wall. An advantage of the treatment method using the device of this invention is that the need for further and sometimes larger incisions across an eye wall to remove an implant, as seen with prior art devices, is removed. The device can be removed and implanted more easily than prior art devices. In addition, when a device with a releasably attached member has exhausted its ability to release a biologically active agent, a member can be removed and replaced without the requirement to make further incisions across the eye wall. An implantable, intraocular, sustained release device according to the present invention may be produced as a kit of components comprising: - a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverse the eye wall having a cross section perpendicular to its axis which is the shape of an axial section through a biconvex lens, b) a member which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period which can be attached to the body portion, and c) a biologically active agent or biologically active agent releasing material which can be placed in the member for release across a biologically active agent releasing surface.

A biologically active agent releasing material includes cells capable of releasing a biologically active agent. It also includes any pro-drug composition in which a biologically active agent is attached or bonded to a matrix from which it is released over time for example by hydrolytic degradation. Description of the Drawings

Figure 1 provides two side views of an implantable, intraocular, sustained release device of the present invention.

Figure 1A shows a device with a retaining flange that rests on the outside of the eye wall.

Figure IB shows a device with a retaining flange that would be counter sunk such that the outer edge of the flange is flush with the outer edge of the eye wall.

Figure 2 shows views from the front end of the present device in the direction shown by the arrow in Figure 1. Figure 2A shows a device with one member and indicates some suitable dimensions .

Figure 2B shows a device with three members Figure 3 shows how a member and a body portion fit together in a second type of the device in which the member is removably attached to the body portion. Figure 3A shows an embodiment in which a member can be removed and replaced from the inside of the eye.

Figure 3B shows the same embodiment as Figure 3 but with the member and body portion separate.

Figure 3C shows an embodiment in which a member can be removed and replaced from the outside of the eye. Figure 3D shows the same embodiment as Figure 3C but with the member and body portion separate.

Figure 4 shows the device of this invention with the retaining flange at an angle other then at right angles to the axis of the body portion. Figure 4A shows a device suitable for use as an implantable, intraocular device providing sustained release in the aqueous humour.

Figure 4B shows body portions of the device with barb(s) to help retain the device in position.

Description of the Preferred Embodiments

An implantable, intraocular, sustained release device, as shown in Figure 1, has a body portion 2 that is positioned in a slit incision in the eye wall and traverses the eye wall and a member 4 attached to the body portion 2, which is adapted so that the distal end extends into a humour of the eye from which a biologically active agent is released over a sustained period. A device is held in position by a retaining flange attached to the body portion at the outside of the body portion. The retaining flange may either rest on the outside of the eye wall 6 or the device may be counter sunk such that the outer edge of the flange 8 is flush with the outer edge of the eye wall.

A device has a tapered front end 10. In order to substantially eliminate any leakage of intraocular fluid around the device, the outside edge of a body portion has a cross sectional shape perpendicular to its axis which is the shape of an axial section through a biconvex lens as shown in Figure 2.

Figure 2A shows that a body portion can have one member attached to it 1 . Figure 2B shows that a body portion can have more than one member attached to it 16. The outside edge of the tapered front end 15 is of the same shape but of smaller dimensions than the outside edge of the main part of the body portion 13. It is generally expected that the retaining flange 12 also has the same shape in cross section.

A first type of implantable, intraocular, sustained release device has a member which is an integral part of the device and is permanently attached to the body portion.

A second type implantable, intraocular, sustained release device has a member which is removably attached to the body portion and can be removed and replaced with another member as shown in Figure 3.

In the second type of the device the body portion has a lumen in which a proximal end 18 of a member is received. The proximal end is held in the lumen 24 and 28 by a deformable flange 20 on the member which fits into a recess in the lumen wall. The distal end of the member 22 is in contact with a humour.

In the device shown in Figure 3A the lumen 24 extends from the end of the body portion 2 in contact with a humour of the eye, part of the way through the body portion 2 of the device . A member 4 is removed and inserted from the inside of the eye. As the lumen 24 does not extend the entire length of the body portion 2 there is no risk of leakage of intraocular fluid via the lumen 24 of the device. To enable a member 4 to be inserted from the inside of the eye, the member is sufficiently mechanically strong to withstand being pushed into the lumen 24 of the body 2 of the device. The distal end of a member 22 has a mechanically stronger section 26 which facilitates manipulation of the member 4. In the device shown in Figure 3C, the body portion 2 of the device has a lumen 28 which extends its entire length. A member 4 is removed and inserted from the outside of the eye. In this embodiment, there is an additional mechanism to prevent leakage of intraocular fluid via the lumen 28 of the body portion 2. A member shown in Figure 3C and 3D has a mechanically strengthened proximal tip 30 to facilitate manipulation of the member.

As shown in Figure 1 a longest dimension of a retaining flange 6 may be at right angles to the axis of the body portion. This type of flange is used for a device in the posterior chamber of the eye for delivery of a biologically active agent to the vitreous humour. As shown in Figure 4 the longest dimension of a retaining flange 32 may be positioned at an angle other than at right angles to the axis of the body portion 2. This type of flange is used for a device in the anterior chamber of the eye for delivery of a biologically active agent to the aqueous humour.

As described above, a second type of device formed in such a way as to encourage bio-integration of the device can also have barbs 34 or ridges 36 on the body portion to assist in holding the device in place.

References Hillery, A. M. et al (eds) (2001) Drug Delivery and

Targetting for Pharmacists and Pharmaceutical Scientists. Published by Taylor & Francis

Koch, et al (1999) Intravitreal endoscopic visulatization of inroxular ganciclovir devices: Improved long-term treatment of CMV retinitis Klin Monatsbl Augenheilkd 214: pl07 MacCumber, M. W. et al (1999) Suture loop to aid in ganciclovir implant removal Arch Ophthalmol . Ill : ppl250- 1254

Martin, F. D. et al (1997) Ganciclovir implant exchange. Timing, surgical procedure and complications. Arch Ophthalmol . 115: ppl389-1394

Neurotech web site http://www.neurotech.fr/technos/encap- cell-d.htm

Claims

1. An implantable, intraocular, sustained release device wherein the device comprises: a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverses the eye wall wherein the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens and b) a member, attached to the body portion, which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and is adapted so that the distal end extends into a humour of the eye .

2. A device according to claim 1 wherein a member is an integral part of the device and permanently attached to the body portion.

3. A device according to claim 1 wherein a member is removably attached to the body portion and can be removed and replaced with another member.

4. A device according to any preceding claim wherein a member comprises a biologically active agent.

5. A device according to any preceding claim wherein a member comprises cells capable of releasing a biologically active agent and preferably the cells are encapsulated.

6. A device according to any preceding claim wherein more than one member is attached to the body portion.

7. A device according to claim 1 wherein a retaining flange to prevent movement of a device further into an eye is attached to the body portion.

8. A device according to claim 7 wherein the longest dimension of the retaining flange is at right angles to the axis of the body portion.

9. A device according to claim 7 wherein the longest dimension of the retaining flange is at an angle other than at right angles to the axis of the body portion.

10. A device according to claim 1 wherein the body portion has a tapered interior end.

11. A device according to claim 3 in which the body portion has a lumen and a proximal end of a removably attached member is received in said lumen.

12. A device according to claim 11 wherein the lumen extends part of the length of the body portion.

13. A device according to claim 11 wherein the lumen extends the whole length of the body portion.

14. A device according to any one of claims 11, 12 and 13 wherein the combination of body portion lumen and surface of a proximal end of a member comprises a deformable section to hold a member in the body portion lumen.

15. A device according to claim 14 wherein a deformable section is a deformable flange which fits into a recess in a lumen wall .

16. Use of a member comprising a biologically active agent releasing surface for release of a biologically active agent over a sustained period and means for releasable attachment to a body portion, with a body portion placed in a slit incision in an eye wall and traversing the eye wall, said body portion having a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens and the combination of a body portion and a member is adapted such that the distal end of the member extends into a humour of the eye .

17. Use of a member according to claim 16 wherein the member comprises a biologically active agent, or a means of producing a biologically active agent .

18. Use of a member according to claim 17 wherein the member comprises a biologically active agent.

19. Use of a member according to claim 17 wherein the member comprises cells capable of releasing a biologically active agent and preferably the cells are encapsulated.

20. Use of a member according to claim 16 wherein said member comprises a deformable flange to releasably attach the member to a body portion.

21. Use of a member according to claim 16 comprising a mechanically strengthened section to enable manipulation.

22. Use of a member according to claim 21 comprising strengthening along its entire length.

23. Use of a body portion positioned in a slit incision in an eye wall and traversing the eye wall, having a cross section perpendicular to its axis which is the shape of an axial cross section through a bi-convex lens, with at least one member which is removably attached to the body portion and a member comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and the combination of body portion and a member is adapted so that a distal end of the member extends into a humour of the eye .

24. Use of a body portion according to claim 23 wherein the body portion has a lumen in which a proximal end of a removably attached member is received.

25. Use of a body portion according to claim 24 wherein the lumen extends part of length of the body portion.

26. Use of a body portion according to claim 24 wherein the lumen extends the whole length of the body portion.

27. Use of a body portion according to any one of claims 24 to 26 wherein the lumen has sections adapted to receive removable attachment means of a member.

28. A method of treating eye disease using an implantable, intraocular, sustained release device comprising: a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverses the eye wall wherein the body portion has a cross section perpendicular to its axis which is the shape of an axial section through a bi-convex lens and b) a member, attached to the body portion, which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period and is adapted so that the distal end extends into a humour of the eye .

29. A method according to claim 28 wherein a member is an integral part of the device and permanently attached to a body portion wherein the processes by which a device can be implanted and removed after use require only one incision across an eye wall.

30. A method according to claim 28 wherein a member is removably attached to the body portion and can be removed and replaced with another member, wherein the processes by which a device can be implanted and removed after use and a member can be replaced require only one incision across an eye wall.

31. A kit comprising :- a) a body portion that is adapted to be positioned in a slit incision in an eye wall and traverse the eye wall having a cross section perpendicular to its axis which is the shape of an axial section through a biconvex lens , b) a member which comprises a biologically active agent releasing surface for release of a biologically active agent over a sustained period which can be attached to the body portion, and c) a biologically active agent or biologically active agent releasing material which can be placed in the member for release across a biologically active agent releasing surface.