Intraocular Lenses

Erik Kroger, December27, 2002

Introduction

It has been estimated that nearly 20 million people suffer from blindness resulting from bilateral cataracts. The word cataract comes from the Greek word for waterfall. In ancient times it was believed that cataracts were caused by a waterfall inside of the eye that impaired a person’s ability to see. A cataract is a condition of white cloudiness that develops on the lens of the eye, resulting from the gathering of normally transparent proteins in the eye lens, resulting in clouded or blocked vision. There is no known natural process of natural reversion for cataract formation with most cases becoming more severe with the passage of time. Currently, the exact physiological process responsible for cataract formation is unknown. It is known to be linked to a variety of factors including, aging, overexposure to UV radiation, traumatic eye injury, diabetes, long term diseases of the eye (uveitis, glaucoma, retinitis pigmentosa, or retinal detachment), family history of cataracts, long term steroid use, or overexposure to x-rays. (WedMDHealth, 2002) Currently, there is no method available cataract treatment other than complete removal of the lens.

Structure

The eyes are complex organs responsible for vision. Their primary purpose is to direct light waves from the outside and refract them onto the optic nerve located in the rear of the eye. The lens is primarily responsible for this directing of light. The lens is a normally clear structure composed of mostly water and protein. It must be of very precise dimensions and properties in order to maintain its role in allowing for functional sight. The lens is located in the forward section of the eye, just behind the iris or colored ring. It is supported by an elastic capsule that prevents lens displacement.

A cataract is the result of proteins in the lens clumping together resulting in a loss of transparency. These proteins usually result in increased opacity, partial or total blockage of the lens or portions of the lens.

Eye image

Intraocular lenses have been designed to replicate the light directing functions a natural lens. Because there is no method available to revert the process of cataract reverseion, lenses containing severe cataracts must be removed in order to restotre vision. Although vision and light detection are possible following the removal of one’s natural lens, lens a replacement (IOL) is necessary for the restoration of visual acuity.

History

People have been surgically removing cataracts for thousands of years. The earliest known mention of cataract surgery comes from a Sanskrit document dating from the 5^th century BC and thought to be the work of the Hindu surgeon Susruta. Instead of removing the lens, he merely dislocated it to the vitreous cavity in the back of the eye. Later the Greeks were know to have produced instruments whereby the cataract could be broken into pieced and then either absorbed or suctioned out of the eye.

In the modern era, surgeons began removing the whole lens through a small incision in the eye. Because of the size and rigidity of the crystalline lens, sutures to aid in wound healing were introduced in 1867. Although all of these procedures did improve patients’ visual capabilities, their vision remained very much impaired due to the removal of the natural lens, leaving the patient unable to focus. In later times, patients were thick corrective glasses. The thickness and necessary design of these glasses gave the patient a distorted view, lacking any significant peripheral vision. Contact lenses also became available, but never gained much popularity. Contacts require a certain amount of maintenance and must be taken out and replaced at certain intervals. The inability of patients of cataract surgery to focus made these tasks extremely difficult.

In 1950, Harold Ridley, then an employee of St. Thomas’ Hospital, implanted the first intraocular lens (IOL). This lens was a clear, polymeric lens that was surgically inserted into the patient’s eyes after the removal the natural lenses. It was composed of Polymethyl methacrylate (PMMA), and proved to be well suited for lens replacement in terms of both structural qualities and biocompatibility. His decision to make the lenses of polymethyl methacrylate was influenced by his experience administering care to pilots involved in aeroplane crashes. At the time, aeroplane windshields were usually composed of Perspex, a polymer that is essentially identical to the PMMA used by Ridley in his implants. Fragments of aeroplane windshields found in these pilots’ eyes proved to have minimal long term effects, especially important was its tendency to causes only minimal amounts of inflammation. His worked progressed through trial and error, eventually proving very successful and giving rise to research that has led to the development of modern IOLs.

The first Ridley lenses made of PMMA were placed just behind the iris and in front of the posterior capsule. There were of course complications following the implantation of these revolutionary lenses. Approximately 15% of those patients who received implants suffered from complications which led to the removal of the implanted lenses. These problems included uveitis, secondary glaucoma, hyphaema, decentration, and dislocation.

The next series of lenses produced were of a closed loop variety, which were supported by the anterior chamber angle. Although the first generation lenses were relatively successful, they left much room for improvement. Most importantly, the old lenses lacked stability because of their reliance on the posterior capsule for support. In an attempt to fix this problem, newer lenses were made to rest on the anterior chamber. This new location not only did not solve the problem of stability, but also resulted in new problems of its own. Lens movement in the anterior chamber led to corneal endothelial damage in all patients. Often this damage led to pseudophakic bullous keratopathy warranting a corneal graft. Because these lenses affected the success rate of corneal grafts, many were removed in order to give the graft a greater chance for success. Other problems associated with these lenses include iris erosion, pupil block, and blood aqueous barrio deterioration caused by iris irritation. In order to prevent these symptoms, many peripheral iridectomies were performed at the time of lens implantation. A peripheral iridectomy is a procedure in which a small hole is created in the iris, connecting the posterior and anterior chamber of the eye, increasing the flow of aqueous materials between the two. These lenses were also associated with cystoid macular oedema (CMO), uveitis, the UGH syndrome (uveitis, glaucoma, hyphaema), and subluxation or dislocation.

Again attempts were made to improve the stability of artificial lens implants. The next generation of lenses sought to do this through physical attachment to the papillary part of the iris diaphragm. These lenses were discontinues after they showed a propensity to dislocate upon sudden pupil dilation. Next attempts were made to attach a lens to the iris using a suture. These lenses failed because of suture degradation over time that eventually led to lens displacement.

These developments led to the introduction of the two major lens types still in use today, anterior chamber and posterior chamber lenses. The modern anterior lenses are very similar to its predecessors’ of the same variety, but structural changes have been made to prevent the high frequency of complications seen in those earlier lenses.

Lenses of the posterior capsule variety have seen a dramatic increase in popularity over the past ten years. This is because complications associated with these lenses are usually much less severe and easily correctable than those associated with anterior capsule lenses. It is necessary to note that insertion of anterior capsule and posterior capsule intraocular lenses involve two different surgical methods for the removal of the natural lens. Cataract surgery with implantation has proved to be a successful treatment of cataracts with approximately 95% of patients experiencing significant improvement in visual acuity.

Surgical Techniques

When speaking of intraocular lenses, it is necessary to understand the surgical procedures involved with both natural lens extraction and artificial lens implantation. The success of an artificial lens is very much affected by the surgical technique used in extraction and implantation. Many of the recent developments in intraocular lenses seek to allow for less invasive surgeries while maintaining the functionality of older lenses.

The first technique developed for the removal of cataract lenses was intracapsular cataract extraction. This process involves the removal of the entire lens as well as the capsule. The capsule is the naturally occurring support system for the crystalline lens, located in the posterior chamber. After intracapsular extraction, anterior capsular lenses can be inserted.

Anterior capsule lenses are associated with severe side effects. These complications are the result of inadequate means of lens support combined with the presence of several very delicate structures in the anterior capsule. These structures include the cornea, iris, aqueous outflow channels and ciliary body.

More recently, extracapsular cataract extraction has become the method of choice for doctors in developed countries. In this process, only the lens is removed, leaving the capsular bag in place. The capsular bag can then be used to support a posterior capsule intraocular lens inserted inside. Before the development of extracapsular extraction, no safe method of posterior capsule intraocular lens support was available, leading to the lens instability mentioned earlier. Because this is the naturally occurring position of the crystalline lens, it tends to offer optical and biological benefits to placement in the anterior capsule.

There are two basic methods for extracapsular extraction, standard and phagoemolsification. Standard removal involves gentle pressure applied to the lens, causing it to become dislocated from the capsular bag. An incision is then made in the cornea through which the lens is removed. After intraocular implantation, the incision is sealed with a suture.

More recently, phagoemolsification has become the extraction method of choice in developed countries. In this technique, a small incision is made into the eye, through which an ultrasound probe is inserted. This probe uses ultrasound energy to break the crystalline lens into small fragments. These fragments are then removed via aspiration. This technique requires a much smaller incision than does standard extracapsular extraction and few, if any, sutures. Both techniques of extracapsular extraction seem to produce similar results after intraocular lens implantation, the only significant differences being complications resulting from the larger incision size in standard extracapsular extraction.

Extracapsular cataract extraction has thus far proved to be a superior alternative to intracapsular extraction, but does have a significant side effect not seen with intracapsular extraction. Extracapsular extration leaves the posterior capsule in place. In some cases this structure becomes clouded a few years after the initial surgery. This cloudiness is the result of epithelial cells gathering in the space between the posterior capsule and the intraocular lens. Currently it is not known what exactly causes posterior capsule opafication (PCO) and it is impossible to predict which patients are most likely to suffer from this condition, although studies seem to suggest that the frequency of PCO decreases as the age of the patient increases. The most common treatment for PCO is Nd:YAG laser capsulotomy. This procedure uses infa-red light to destroy the optical tissues of the posterior capsule, creating a cleared area in posterior capsule. The remaining tissue surrounding this cleared area usually folds back out of visual range following surgery. This procedure can produce complications of its own, including increased intraocular pressure, inflammation, intraocular lens dislocation, cystoid macular edema, disruption of the vitreous face, damage to the intraocular lens, and increased occurrence of retinal detachment.

Intraocular lens Research and Requirements

Research concerning the benefits and drawbacks of each lens type are markedly incomplete. This is because new foldable acrylic and silicone lenses are relatively new to the market and lens comparison, in order to be thorough and accurate, must compare a wide variety of factors. It would be incredibly expensive and time consuming if one group of researchers tried to compare all of the important factors of intraocular lenses for all of the many lenses currently on the market. It is for this reason that physicians need to piece together all the comparative data that exists and attempt to determine which results are material related and which are design related as many lenses of different materials also have different designs and shapes.

A potential lens must, of course, be biocompatible. The quest for biocompatibility is a never ending one. For a structure to be biocompatible within the body it should be capable of performing a specific function without causing an undo bodily response over either the short or long term. Because no material is completely inert within the body, all implants have some sort of negative interaction with the body. Deeming something biocompatible, merely means that these interactions to not significantly inhibit or diminish the implant’s intended function. All implants have the potential to cause adverse reactions or side effects and generally the most biocompatible implant will be that which reduces the frequency and severity of those side effects.

IOL biocompatibility within the human eye has three major aspects. These are the effect on the blood aqueous barrier, the cellular reaction on the anterior surface of the lens, and the effect on the lens capsule. Blood aqueous barrier changes can be assessed by the amount of inflammation (flare and cells) within the anterior chamber, which can be quantified using the laser flare and cell meter. Cells on the anterior surface of the implant can be examined post-operatively using specular microscopy and have been used extensively as a method of assessing the foreign body response to the IOL. The effect of the IOL on the capsule consists of lens epithelial cell proliferation and metaplasia leading to anterior and posterior capsular opacification, and IOL decentration.

The long term biocompatibility of an implant is determined not just by chemical properties and the rate at which the material is degraded within the body. It is also determined by the physical and mechanical properties of the lens as well as the supporting haptic. The supporting haptic need not be and often times is not composed of the same material as the adjoining intraocular lens. However, haptics are usually offered in only those materials that are also used in intraocular lenses (silicon, acrylics, and PMMA). Haptics are offered in a variety of forms plates, discs, C loops, J loops

Intraocular lenses usually vary in physical design as well as in material related properties such as water content, refractive index, clarity, surface properties, and mechanical strength.

Types of lenses

Currently, IOLs composed of four basic materials are available for lens replacement. Lenses of silicone, acrylics (both hydrophilic and hydrophobic), and PMMA have all been proven safe for implantation in patients. Each material provides its own specific advantages and disadvantages. All are currently undergoing research, not only to determine if current lenses present any unexpected long term problems, but also to learn which materials contain properties conducive to new lens designs.

PMMA remains the standard material against which all others being considered for use in intraocular lenses are tested. It was the first material used in an intraocular lens remains the most common material used worldwide, largely because of it is time tested and relatively cheap to produce. The primary weakness of PMMA is that it is inflexible and as such, requires a relatively larger incision for implantation when compared to recent foldable silicon and acrylic lenses. Newer, foldable lenses of other material have entered the market in the past few years. The primary advantage of these lenses is that they can be folded or rolled prior to insertion into the posterior capsule, allowing for a smaller incision size and faster recovery. These lenses are still relatively new, and being such, have not been proven through experience as have their PMMA counterparts. Preliminary tests comparing the effectiveness and efficacy of lens of different materials seems to show advantages and disadvantages of each, with no material proving significantly superior to the others.

The advent of phagoemulsification sparked interest in new lenses made of less rigid materials. These lenses can be folded or rolled, allowing for insertion through a much smaller incision than needed for the insertion of traditional PMMA lenses. A smaller incision is thought to be benefitial because it allows for faster recovery and less traumatic changes to eye shape, reducing the frequency and severity of postoperative astigmatism. These small incisions are also beneficial in that they do not require a suture for proper healing. Early attempts at producing a foldable IOL, however, were unfruitful, because they elbowed and folded as the capsular bag contracted. The primary disadvantage associated with foldable lenses as a whole is cost. Foldable intraocular lenses tend to cost three to fives times as much as PMMA lenses.

Silicone Lenses

Silicone lenses are one commonly used type of foldable intraocular lens. The advantages of silicone lenses are basically the same as with other commonly used foldable intraocular lenses, but it does have some unique disadvantages.

As with all current intraocular lenses, some patients develop some degree of posterior capsule opafication following the implantation of a silicone lens. Severe cases are treated by using Nd: YAG laser radiation. Silicone lenses have been found to have a low threshold for damage when exposed to this treatment. Silicone lenses have shown to be more prone to laser induced damage than either PMMA or acrylic lenses.

Silicone lenses also tend to be very slippery when wet. All intraoculular lenses are moistened before implantation, so this property of silicone can make folding and implanting the lens very difficult. Also, silicone IOLs with flexible haptics or

plate haptic design have a higher incidence of decentration than other IOL types. Plate

haptic silicone intraocular lenses are also prone to contraction of the anterior capsule opening.

Silicon lenses have also been reported to occasionally rupture the capsular bag during unfolding. This is because the lenses tend to unfold in a very quick and uncontrolled manner, causing damage to the delicate surrounding tissues.

Hydrogel Lenses

Hydrophilic acrylic or hydrogel lenses are also quite common, although their popularity has weaned in recent years due to high incidences of severe PCO formation following implantation. Because the lenses are hydrophilic, they tend to be less prone to denaturation caused by proteins, allowing them to retain their smooth surface and trigger fewer biological defense mechanisms.

Hydrophobic Acrylic Lenses

AcrySof, which is produced by Alcon and an example of a hydrophobic acrylic IOL, has become the most commonly used IOL in the USA. The chemical structure of hydrophobic acrylics is very similar to that of PMMA, containing many of the same backbone elements. The higher refractive index of hydrophobic acrylics has both advantages and disadvantages. It allows for lenses to produce lenses that are thinner than comparable silicone or PMMA lenses, but there have been reports of increased frequency and severity of glare.

Acrylic polymers change their mechanical properties with temperature, being hard and

glassy at low temperature, and soft and fluid at high temperature. This means that an IOL

inserted at room temperature unfolds slowly and in a controlled manner. This property prevents the sort of damage often associated with the rapid unfolding of foldable silicone lenses. This property does mean that lenses must be warmed slightly in order to be soft enough for implantation. Also, hydrophobic acrylics tend to have an almost sticky nature. This allows them to stick to the posterior capsule and it is believed that this interaction helps to reduce the amount of PCO formation. Unfortunately these lenses also have a tendency to stick to the forceps and hands of the surgeon, occasionally making implantation difficult. This characteristic may mean that the IOL sticks to the capsular bag (which is discussed

The AcrySof IOL has been found to be associated with dramatically reduced rates of PCO. This is thought to be due to both mechanical and material features. This was the

first lens implant to be manufactured with a square optic edge, and it is thought that this

edge acts as a barrier to the movement of cells onto the posterior capsule, inhibiting PCO.

. Recent Studies

In order to prove the connection between lens shape and posterior capsule opification, a team of doctors studied the development of PCO in two similar acrylic lenses. The lenses used were both produced by Allergan Surgical, models AR40 and Ar40e with rounded and sharp posterior edges respectively. One year following implantation, eyes containing Ar40e lenses were shown to contain significantly less PCO than those containing the AR40 lenses. Measurements of PCO were made both subjective slit lamp and automated image analysis software. The results of the objective computer aided studies were based upon the software programs ability to find inconsistencies in retroilluminated images of patients eyes that would indicate the presence of PCO. (Buehl)

Another recent study compared the posterior capsule opafication in eyes with PMMA, silicon, and acryclic IOLs. The degree of PCO was determined objectively through the use of a specially designed computer software program. The study found that PCO progression in eyes with PMMA lenses was significantly greater than in eyes with either silicone or acrylic lenses. This suggests that silicone and acrylic lenses are more effective at preventing postoperative PCO. (Hayashi)

A recent study compared hydrophobic acrylic, hydrophilic acryilic, and silicone lenses. This study found increased formation of PCO in eyes in which hydrophilic acrylic lenses had been implanted. The study also found that hydrophilic acrylic lenses had better uveal biocompatablity than did hydrophobic acrylic lenses. Hydrophobic acrylic lenses showed higher capsular biocompatablity than did hydrophilic acrylic lenses. Silicone also showed poor uveal biocompatibility but very good capsular biocompatibility. (Abela-Formanek)

A study was done recently to determine the effects of lens design on postoporive glare. The study compared commonly used silicon, polymethyl methacrylate and acrylic lenses of different optic designs and analyzed using a computer program which grades the by measuring the size of the deflected glare image at the retina. The study found that unequal biconvex designs produced a greater degree of glare than did those of equi-biconvex design. The program determined the glare in unequal biconvex lenses to be sixty times that of equi-biconvex lenses. The study also found that lenses composed of materials with higher index of refraction indexes such as acrylics produced more glare than lenses composed of materials with lower indexes of refraction such as silicone. Silicone has the lowest refractive index (1.43) and acrylic has the highest (1.55). It was determined that acrylic lenses produce five times the amount of glare produced by silicone lenses. The study determined that if minimal glare is desired acrylic lenses made with an unequal biconvex design should be avoided. (Erie)

Another study measured the movement of the anterior capsule following implantation of an intraocular lens, through studies of PMMA, acrylic, and silicone lenses. They found that capsule movement was greatest within the first three months following surgery and was statistically significantly less for AcrySof compared to PMMA and silicone IOLs. (Ursell)

PMMA remains the world’s most popular choice for intraocular lenses because it has many advantages including not being biodegradable in the eye, being resistant to damage caused by infrared light, having the ability to maintain a smooth surface even when in contact with active tissues, and causing only a minor inflammatory reaction. Probably the most convincing benefit of PMMA lenses however, is cost. Whereas most acrylic lenses cost about three to four hundred dollars, and most silicone lenses cost around two hundred dollars, PMMA lenses are often available for around fifty dollars. (Harstall) However, one disadvantage is that it is rigid and so requires a larger incision for insertion than the newer foldable materials. Surface modifications of PMMA with heparin have been found to reduce the inflammatory cell precipitates found on the anterior IOL surface post-operatively.

Future

Currently trials are being conducted for a variety of potentially revolutionary technologies for intraocular lenses. These include multifocal and accommodative lenses, both of which hope to eliminate the patient’s need for glasses following the insertion of an intraocular lens. These lenses attempt to help the eye to adjust to focusing on objects at different distances. Accommodative lenses attempt to do this through slight changes is form while multifocal lenses use rings of varying optical strength. Current accommodative lenses produce massive amounts of PCO because the shape changes cause openings between the lens and the capsular bag. Multifocal lenses are very close to being approved for insertion. The field of intraocular lenses is exciting and rapidly changing. The new technologies of today could very well be outdated in the matter of a few short years.

Conclusion

Intraocular lenses have improved the lives of millions of people around the world. Hopefully as technologies continue to improve, intraocular lens insertion will become less traumatic to the eye while improving the results.

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