11/19/14 When it comes to medical interventions in the eye, miniaturization is obviously key, especially when the device in question is to be permanently or temporarily implanted.
Micro Engineering Solutions (MES) is dealing with more and more inquiries from medical device OEMs working in the area of intraocular lenses (IOLs) and drug delivery devices for treatment of various eye diseases. Many of these applications push at the very boundaries of what is possible in the area of medical design and the micro manufacturing technologies and techniques that can realize these designs, and as such it is becoming an exciting area for product development.
It is also an area that requires any medical device manufacturer to tread carefully, and to always work with a qualified and expert micro manufacturing company such as MES that can advise on design for manufacture, material, assembly, and all other considerations when manufacturing in the ultra precision arena.
When it comes to drug delivery devices for use in the eye, their use is a product of the difficulties inherent in targeting drugs to the posterior segment of the eye. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and “tearing”. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior eye segment, and injections are quite often rendered less than effective due to the fast flowing blood supply to the region which leads to rapid clearance rates and therefore causes drug concentrations to diminish rapidly. So it is that focus that is being placed on polymeric sustained drug release systems that can be implanted in the eye.
These systems are often prepared using different kinds of biodegradable polymers, the polymer which contains the drug degrading slowly in physiological conditions and so controlling the slow release of the drug. Polymers such as PLA, PGA and PLGA are often used for such applications, all being aliphatic polyesters that can be degraded by enzymatic and non-enzymatic hydrolysis.
The design and manufacture of such combination devices, and the use of materials such as PLA and PGA play to many of the strengths of MES, which has worked on numerous projects using often difficult to mold biodegradable / bioresorbable materials. MES also has extensive experience in the regulatory environment that surrounds such combination devices, and would welcome any inquiries from OEMs working with such applications.
When it comes to micro manufacturing and implantable ophthalmic applications, however, the most vibrant area for commercial applications is IOLs.
IOLs are typically used for the treatment of cataracts or myopia. The most common IOL is what is termed the “pseudophakic” IOL, implanted during cataract surgery after the damaged lens has been removed. The implanted lens provides the light focusing function previously undertaken by the original lens. Another type of IOL is the “phakic” lens, which is placed over an existing natural lens, and is used in refractive surgery to change the eye’s optical power as a treatment for myopia or nearsightedness.
IOLs are most commonly manufactured from plastic, and consist of a small plastic lens and two plastic side struts or “haptics” to hold the lens in place within the eye. Various materials have been used to manufacture IOLs over time including PMMA, silicone, hydrophobic acrylate, hydrophilic acrylate, and collamer. PMMA was the first material to be used, but was inflexible, and has more recently been replaced by flexible alternatives that allow the lens to be folded, and therefore inserted through a smaller incision in the eye.
Material choice is obviously key. Not only does the IOL need to be flexible and totally transparent, but it should be characterized by low residuals and precise and isotropic expansion. Pure forms of hydrophilic and hydrophobic acrylic materials are often used for these reasons. Such materials exhibit elasticity and tensile strength to ensure that they bounce back to their original shape after being folded and passed through extremely small incision holes, sometimes as small as 1mm.
Dimensional stability is critical, and differentiates basic and superior IOLs. If material selection is not optimal, molded lenses will not be dimensionally stable, and they may also be prone to shrinkage over time when used, thereby compromising their efficiency.
An unrelenting eye also needs to be focused on the manufacturing processes used for making IOLs. With the level of demand for IOLs, manufacturing processes need to be geared for mass manufacture, and process control is an absolute must with zero failure rates a given. Proper process control ensures satisfied end users, but also guarantees quality manufacturing.
Today, demand means that IOLs must contain both surface structures at the nanometer level, and aspheric designs with spherical and cylindrical shapes in differing axes. There are several different ways to manufacture the lens, but the two main ways are either cutting on a lathe, or molding the lens by forming or injection.
Cast molding is the primary manufacturing method used for producing the more complicated lens designs. This method uses front and back curve molds that are typically molded from a “master pin” tool that is machined using a diamond blade. This master pin contains the nanometer-level structures that must be accurately replicated on the lens. Different master pins are used to create the front and back curve molds. These molds are assembled in mold inserts, and polymer is injected into the mold and thermally cured. The lenses are then hydrated where they absorb 20-70% water by mass.
Before each master pin can be used to make production molds, it must first be tested by building a trial mold that is used to produce a limited pilot run of lenses. These lenses are then tested to see if they provide the right prescription. Quite often, there is some variation from required parameters, so the pin needs some re-engineering and re-machining. MES has seen instances where this process of testing and re-engineering can occur up to 6 times before production of the required prescription is attained. This is a huge drain on resources and time, and so once again flags up the need to work with qualified micro engineering professionals from an early stage in product development.
Molded lenses also require a number of process steps before they are ready for customer use, including lapping, trimming, and polishing of the lens to eliminate any potential protrusions, pits and edge burrs that could potentially cause eye irritation. All molding and post-molding activities must of course ensure that the lens is not contaminated by plasticizers, mold release agents, lubricants, and anti-oxidants.
When machined, IOLs go through front-side machining, and second-side machining, the key being to ensure no loss of precision as the lens moves from collet to collet. Processes have been developed that overcome the time-consuming and costly requirement to measure the position of the surface before starting to lathe. As with molded IOLs, after machining, a hydration process takes place, and quite often these hydrated IOLs are tumble polished to finish.
The quality control process to ensure the integrity of finished and pilot run IOLs has long been an area of concern. Use of Fizeau laser interferometers struggle to produce accurate measurements of modern IOLs for a variety of reasons, and 2D stylus metrology devices are contact-based solutions which may damage the IOL being measured, and slow. Because of this, many advocate the use of 3D optical microscopy measurements which use white light interferometry (also know as optical profiling) to accurately measure 3D surface roughness and profiles of the IOLs under test. An advantage of the 3D optical microscope is that a complete 3D surface measurement provides a much greater holistic representation of the lens surface than is produced using a 2D stylus, and this can greatly reduce the need for additional and costly iterations and reworking of the IOL master pins.
MES has end-to-end experience of the manufacture of IOLs, from design through manufacture, and testing. The company is also expert in micro molding applications, and can therefore provide vital insight and experience when it comes to the complex process of molding ophthalmic lenses. OEMs working in this area and the area of ophthalmic drug delivery devices must partner with companies such as MES that have a profound understanding of the micro manufacturing arena.