Corneal Membrane Transplant Injector

Small Business Innovation Research Proposal- Revision 2April 13, 2007

Kristen Berger, Paul Bieniek, Dave Brooks, Marie Gill Advisor: Ahmed Al-Ghoul

Corneal Membrane Transplant Injector

SBIR Grant Proposal

Kristen Berger

Paul Bieniek

David Brooks

Marie Gill

Advisor:

Ahmed Al-Ghoul, MD

Table of Contents: page

Specific Aims3

Significance3

Relevant Experience4

Methodology5

References11

A. Specific Aims

Approximately half of the cornea replacement surgeries performed unnecessarily replace the entire cornea. This total replacement causes significant damage to the eye and the cells of the donor tissue. Recently, surgeries have been developed that replace only Descemet’s membrane and the endothelial cells and are much less traumatic for the eye. This Phase I program proposes a corneal implant injector that would deliver the donor tissue, with minimal damage to the endothelium, through a smaller incision in the eye. This device would also maintain the pressure in the anterior chamber through irrigation during surgery.

The Phase I specific aims are:

Design a device that delivers the cornea tissue into the eye in a manner involving less damage to the tissue and the eye, while maintaining intraocular pressure.

Our device is designed to be compatible with phacoemulsification machines used in cornea transplant surgeries. The tip of the injector attaches to the stroma side of the cornea tissue via suction through two small ports, thus minimizing contact with the viable tissue. The tip also has a port for irrigation which is used to maintain intraocular pressure. The opening of the cartridge that surrounds the tip fits into a 4 mm incision in the eye. This combination of features will minimize damage to the tissue and the eye, while facilitating delivery of the tissue into the eye.

Fabricate functional prototypes.

Using the design created with SolidWorks, a model of the injector will be produced using an SLA machine. Once the design is perfected, the cartridge will be molded or pour-casted from a clear plastic. The rest of the injector will be made from stainless steel or titanium. The parts will then be hand-assembled by the researchers.

In vitro testing.

Once a working prototype is built, it will be tested on non-living animal models. After functionality has been proven on animal eyes, trials with human eyes will be completed.

B. Significance

Cornea transplant surgery, or keratoplasty, is a procedure for treating diseases of a patient’s cornea. These diseases include infections, injuries and genetic predispositions to cloudy corneas. In 2005, over 100,000 cornea transplant surgeries occurred throughout the world [1]. Cornea transplant surgery involves surgically removing a patient’s entire cornea and replacing it with a donated cornea (like many other organ transplants). This procedure is excessive because it is often the case that only a small part of the cornea is damaged, but many healthy parts of the cornea are replaced regardless [2].

Recently there has been a rapid evolution of surgical techniques to improve upon the flaws of standard keratoplasty. The newly developed Descemet’s Stripping with Endothelial Keratoplasty (DSEK) allows surgeons to replace only the diseased portion of the cornea known as the Descemet’s membrane. Lying on the posterior wall of the cornea, this membrane can be scored, removed, and replaced through a small lateral incision on the eye. This allows the incision to be closed with one small suture instead of the 8-10 sutures required for complete cornea replacement [3].

Even though keratoplasty methods have increased in sophistication, there still are issues with the procedure. The major issue we wish to address is damage to the donor tissue during implantation. Current procedures involve folding the donor tissue (a very thin piece of tissue about the size of a dime) and pushing the folded tissue through an incision about four millimeters long, as shown in figure 1. This form of implantation often damages the cells and adversely affects the patient’s vision after the procedure. If a means to inject the tissue could be made then the hole could be made even smaller and the tissue would be damaged less during implantation. The goal of our Phase I program is to develop a device to accomplish this task with the ultimate vision of helping to improve the efficacy of DSEK procedures.

Figure 1- In current keratoplasty procedures, the donor membrane is

folded into a “taco” and inserted into the eye through a small incision

using tweezers, as shown here. This step can be damaging to the tissue [3].

C. Relevant Experience:

The Corneal Membrane Transplant Injector design team consists of four University of Pittsburgh Department of Bioengineering students and their mentor, Ahmed Al-Ghoul ofThe Eye & Ear Institute.

David Brooks is in the Biosignals and Imaging concentration. He currently works in Dr. John Patzer’s lab performing signal analysis of Doppler ultrasound graphs to derive intercranial pressure for human patients. In the past, he has performed research with cell cultures,using rat muscle stem cells. David also has small business experience. His family owns businesses that revenue over six hundred thousand dollars annually. He has hands on experience with management, financing, and book keeping.

Marie Gill is also in the Biosignals and Imaging concentration. Most recently she has worked at the Positron Emission Tomography Center in UPMC Presbyterian under the mentorship of Dr. Charles Laymon. Her research focused on the quantification of the effect of insulin stimulation on glucose transport in skeletal muscle.

Paul Bieniek is in the Biotechnology and Artificial Organs concentration. He has workedfor two years in Dr. Michael Sacks' lab programming for tissue mechanics tests. His current research involves modeling the strains experienced by artificial and native porcine heart valves during physiological mimicked beating.

Kristen Berger is also in the Biotechnology and Artificial Organs concentration. She has workedfor 3 semesters at Medrad, (two semesters in the Magnetic Resonance Department, and one in the Product Innovations and Advanced Development group). Her experience includes designing a Matlab GUI to analyze contrast enhancement in sequences of CT scans, designing an infrared imaging phantom, and doing pressure and flow rate accuracy testing for cell delivery injectors.

Dr. Ahmed Al-Ghoul is a Clinical Fellow in Cornea, External Diseases and Refractive Surgery. He is also a Clinical Instructor in Ophthalmology. After a tangible design is produced, Dr. Al-Ghoul will personally test the effectiveness of the injector with donor eyes as seen in Figure 1. With Dr. Al-Ghoul’s expertise in ophthalmology and the collective experience in design techniques and engineering principles shared by the four engineering students, there is great potential for a successful Corneal Membrane Transplant Injector.

D. Methodology

Our Phase I work plan will aim to complete the following tasks with regard to our specific aims:

Specific Aim 1: To design a device that delivers the cornea tissue into the eye in a manner involving less damage to the tissue and the eye. The device will also maintain intraocular pressure.

In order to design a device capable of performing the necessary tasks, we first needed to fully understand what was intended to be accomplished. To increase our knowledge of the task at hand, we met extensively with Dr. Al-Ghoul during the beginning weeks of our Phase I project. Beginning with initial brainstorming think tanks, we proceeded to watch videos of the procedure, observe Dr. Al-Ghoul’s demonstration of similar instruments, and study the operation of the phacoemulsification machine with which our device must cooperate. Figure 3 shows the initial 2 design ideas that were generated.

Figure 3- a.) One initial design schematic involving the folding of the donor membrane before insertion. b.) A second design schematic that involves wrapping the membrane around the tip.

With initial design schematics in hand, we proceeded to create SolidWorks models. With continued consultation with Dr. Al-Ghoul, these models evolved and combined to form a final computer model that addressed all of the proposed necessary requirements of the device as listed in the PDS:

Client Requirements

• Must be simple to operate
• Must deliver corneal tissue into the recipient’s eye
• Must contact only the stroma side of the tissue
• Must hold the tissue in place with suction only
• Must be inexpensive to produce
• Must be sterilizable with an autoclave
• Must have a disposable, transparent plastic cartridge
• Must have an oval tip no greater than 4mm wide by 3mm tall
• Must maintain anterior chamber pressure via buffered saline solution (BSS) irrigation
• Must be compatible with existing phacoemulsification equipment made by Alcon, Advanced Medical Optics, and Bausch & Lomb.
• Must be less damaging to the eye and the endothelial cells of the donor cornea tissue than the current method, which involves folding the cornea tissue in half twice with forceps and inserting it into a 4-5 mm incision in the eye

Figure 4 shows the progression of the computer model from beginning to the current model. The model was designed to have a mobile injector that inserts the cornea membrane into the patient’s eye. Integrated in this injector are two suction ports that adhere to the membrane with negative pressure and an irrigation port that delivers buffered saline solution (BSS) into the anterior chamber in order to maintain intraocular pressure. The opposite end of the injector was designed to connect to the irrigation and aspiration hoses of the phacoemulsification machine.

We acknowledge that throughout the Phase I process, testing will warrant subsequent design modifications and improvements. Therefore, the models presented herein are part of an ongoing evolution of our Phase I prototype.

Figure 4- SolidWorks models of the Phase I Corneal Membrane Transplant Injector device. a.) A preliminary model for folding the membrane. b, c.) Preliminary models incorporating suction adhered membranes wrapped around tip. d.) Current design model.

Specific Aim 2: Fabricate functioning prototypes.

Our first step in production of our Phase I prototype was to produce a wax model of the design. The purpose of this model is simply to produce a physical model to conceptualize the size of the device. Three-dimensional models on a computer screen can be deceptive in size. The wax model gives a better feeling of the scope of the device, and it also allows the surgeon to hold the device and provide feedback on how the size and dimensions actually feel. This preliminary evaluation allows for simple corrections in the length, width, or aesthetics of the device to be modified before more expensive production is pursued.

A particular problem with the more advanced production stages was the necessity for different materials and production methods for the two components of our device. These components are shown in figure 5.

Figure 5- SolidWorks models of the two components of the device. a.) the cartridge was made from an SLA resin and b.) the injector was made from stainless steel parts.

The cartridge will be constructed of a clear polymer so that the operating surgeon will be able to see the donor membrane inside the device before insertion. The material used must also be strong to ensure that the thin wall of the cartridge at the tip (>0.3mm) does not fail. In addition, repeated interaction with a moving metal part requires that the material be durable and resistant to abrasion. Finally, the cartridge material must be resistant to water and isopropyl alcohol for purposes of use and sterilization.

The polymer chosen for the cartridge prototype was Somos Watershed 11120 (DSM, Heerlen, Netherlands), a stereo lithography(SLA) resin often used to develop medical concept models. This material was preferred due to its fulfillment of the strength, durability, and liquid resistance properties required for our design.

For a mass produced cartridge, the material requirements will be strength and water resistance. The durability and sterilization requirements will most likely not be important as we foresee the creation of a disposable cartridge. This part would be injection molded from acrylonitrile butadiene styrene (ABS), a plastic similar to the one used in the prototype. Injection molding was chosen because it is the cheapest and fastest method for increasing the scale of manufacturing to mass production.

The injector was hand assembled from purchased and machined stainless steel parts. Stainless steel was chosen for the material because it is used in many surgical devices and has proven biocompatibility. In addition, it is non-corrosive and extremely durable, making it suitable for repeated use with autoclaving in between procedures.

The triple lumen tip of the injector (two suction and one irrigationconduit) was composed of three pieces of hypodermic tubing inside a larger tube that was compressed to form an oval. The tip of the oval tube was capped with a tiny rounded tip that was fabricated using SLA. The main body of the injector was machined on a lathe from a solid piece of stainless steel. A manifold was also machined to screw onto the main body. It incorporated threads for attaching three luer fittings that are compatible with the phacoemulsifier machine that provides suction and saline irrigation. Each of these fitting was affixed to one of the hypodermic tubes with PVC tubing. Finally, a small pin was fabricated and inserted into the outer wall of the injector to fit into a guidance track in the cartridge and insure alignment of the parts.

The parts were then assembled together, bonded with epoxy, and adjusted to fit properly. The post-fabrication modifications included sanding and curing of the cartridge, bending the injector tip, and increasing the depth of the o-ring grooves. The final device can be seen in figure 6.

Figure 6- The completed corneal membrane transplant injector.

For mass production of the injector, several different methodologies were investigated. Computer numerical control (CNC) machining was considered but high costs (~$100 per injector based on prices for similar parts) and longer production time made this type of fabrication undesirable. Rather, metal injection molding (MIM) was selected as the best fabrication method because of cheaper costs (~$20 per injector) and faster production time. This method is already used for the production of many stainless steel surgical devices.

Specific Aim 3: In vitro functionality testing.

Before a final prototype was fabricated, we constructed a concept model to test the two main functions of the device: irrigation and suction. This preliminary testing was performed using silicone corneas because they are comparable to the size of a corneal membrane. Irrigation and suction were achieved using this concept model (Fig. 7).

After the final prototype was finished, we again tested that the device could provide irrigation and suction using silicone corneas (Fig. 8). The device was then given to Dr. Al-Ghoul to begin trials on animal cadaver eyes. He first checked to see if the device was compatible with the phacoemulsification machine, which it was. Currently, he is conducting tests on goat eyes to assess the potential of the Corneal Membrane Transplant Injector. He will retrieve a donor corneal membrane from one cadaver eye and use the device to deliver it into a recipient cadaver eye. Dr. Al-Ghoul’s results from his tests will be qualitative in nature and will have two main foci: ease of use and functionality. He will follow a qualitative testing matrix that requires him to rate different features of the prototype and surgery from poor to excellent. These features include ergonomics, incision size, procedure time, irrigation, and suction. Histology testing will be performed to assess if the donor membrane or the recipient eye accrued any damage. With Dr. Al-Ghoul’s feedback, design improvements will be made, new prototypes will be constructed, and another round of testing will begin.

It is our hope that the circular pattern of our methodology- from design to production to testing- will continue until a final effective prototype is developed. The ultimate goal of our Phase I process will be the incorporation of the corneal membrane transplant injector into the DSEK procedure. This will ultimately help surgeons perform the procedure and will allow patients a decreased recovery time and complications.

Figure 7- The concept model used to test irrigation and suction.

Figure8- Preliminary testing of final prototype using silicone corneas. a.) Suction b.) Irrigation

References:

1. Miller, Liana. Introducing Laser Corneal Transplantation – the Procedure’s Greatest

Advancement in 50 Years. PRNewswire. October 26, 2006.

2. Grayson, Charlotte, E. Automated Lamellar Keratoplasty Eye Surgery (ALK).

MedicineNet. November 12, 2006.

3. Gorovoy, M. S., Francis, W. P. New Technique Transforms Corneal Transplants.

Cataract and Refractive Surgery Today. Nov/Dec 2005. pp55-58.

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