BIOMATERIALS GROUP

INTRAOCULAR LENSES

Burak MUTLU, 10.01.2002

ABSTRACT

Eye is the vital organ in everyday life for recognizing the images around us. Due to age or some other outer factors the structure of the eye damaged and it cannot function properly. Cataract is one of these disorders, which is caused by the opafications on the transparent crystalline structure of the lens of the eye. The only method of curing cataract is surgery, which involves the removal of lens while leaving its capsule behind and implanting the Intraocular Lens instead. In this report, firstly information about general anatomy of the eye was given, and then the causes and treatments of cataract followed by properties and recent developments in Intraocular Lenses were given.

I would like to give my special thanks to Dr. Mustafa Onat for his infinite support and great helps throughout this research.

TABLE OF CONTENTS

I. Anatomy of the Eye............................................................................................. 1

1.1 Gross Anatomy and Physiology of the Eye................................................................ 2

1.2 External Features of the Globe.................................................................................. 2

1.2.1 Scleral/Corneal Layer....................................................................................... 2

1.2.2 Vascular/Chorodial Layer................................................................................. 2

1.2.3 Retinal Layer.................................................................................................... 3

1.3 Internal Feature of the Globe.................................................................................... 3

1.3.1 The Aqueous Humor........................................................................................ 3

1.3.2 The Viterous Humor......................................................................................... 3

1.3.3 The Lens.......................................................................................................... 4

II. CATARCT..................................................................................................................... 5

2.1 Causes and Symptoms of Cataract........................................................................... 5

2.2 Treatment of Cataract............................................................................................... 6

III. intraocular lenses......................................................................................... 7

3.1 PMMA IOLs........................................................................................................... 7

3.2 Foldable IOLs.......................................................................................................... 8

3.3 Developments of Materials....................................................................................... 9

3.4 Complications of Foldable IOLs............................................................................... 10

iv. referances............................................................................................................ 12

I. ANATOMY OF EYE

The eye is a complex structure that receives and translates light into impulses that our brain recognizes as images (Figure1). It is a nearly spherical hollow globe filled with fluids (humors). The outer layer or tunic (sclera, or white, and cornea) is fibrous and protective. The middle tunic layer (choroid, ciliary body and the iris) is vascular. The innermost layer (the retina) is nervous or sensory. The fluids in the eye are divided by the lens into the vitreous humor (behind the lens) and the aqueous humor (in front of the lens). The lens itself is flexible and suspended by ligaments which allow it to change shape to focus light on the retina, which is composed of sensory neurons. The human eye is a complex organ of vital importance for everyday life and a major target for a range of implants and accessory biomedical devices.

The physological structure of eye can be divided into three main parts: (i) Gross anatomy and physology of the eye, (ii) External Features of the Globe, and (iii) Internal Features of the Globe.

http://www.nlm.nih.gov/medlineplus/ency/imagepage/1094.htm

Figure1: Structure of the Eye

1.1 Gross anatomy and physology of the eye

The eye is mainly a soft tissue called the eyeball or globe. The globe is placed within the skull into an eye socket or the orbit. The orbit exceeds in the size of globe and the space between them is filled with fat and with a sheet of connective tissue. The linkage of the globe to central nervous system is achieved via the optic nerve.

1.2 External Features of the Globe

1.2.1 Scleral/Corneal Layer

This is the outer, slightly elastic collagenous layer. Posterior region of the layer is opaque and forms the sclera. The anterior part of sclera is visible at the surface and it is the white of eye. The foremost anterior sclera forms a specialized transparent layer known as cornea.The cornea is a transparent, avascular tissue with a highly ordered structure which minimizes the scattering of light. It is composed of three layers with a stratified epithelium on the anterior surface, a collagenous stroma comprising the bulk of the corneal thickness, and a layer of endothelial cells on the posterior face bounding the anterior ocular chamber. The endothelial cells, although capable of cell division, repair by cell enlargement usually. Thus, minimisation of endothelial cell damage is the main requirement on the development of ocular biomaterials.

The cornea and anterior sclera are protected against injury and particulate abrasion by the Eyelids and the Lachrymal System.

Many biomedical implants interact directly with the ocular surface and scleral layer including: keratoprostheses, contact lenses, lachrymal plugs and glaucoma filtration implants.

1.2.2 Vascular/Choroidal Layer

The majority of the vascular layer is pigmented which prevents the light scattering with in the globe. At the junction of the sclera and cornea choroid thickens and forms ciliary body, which is responsible for the production of aqueous humor. Anterior to the ciliary body is the iris. The iris (and ciliary body) is muscled and controls the size o pupil by contraction and relaxation of radial and circular muscle fibers.

Only few bioengineered devices interact directly with the choroidal layer, but the efficiency of all implantable systems is heavily influenced by the production of aqueous humour maintained by the ciliary body.

1.2.3 Retinal Layer

The retinal layer is a complex ennervated structure covering approximately two-thirds of the internal posterior surface of the globe. Light passes through the entire thickness of the retina to affect underlying cells containing photosensitive pigment; these cells are known as the rod and cone cells.

Relatively few devices are designed to interact directly with the retina. One promising example is the scleral buckle, which is a device designed to promote reattachment of the retina.

1.3 Internal Features of the globe

1.3.1 The Aqueous Humor

The lens and the cornea receive nutrients via the aqueous humour since they lack direct blood supplies. It is produced by ciliary body, passes through the pupil into the anterior chamber and drains away via the trabecular network. As a result of this process the globe has a measurable intraocular pressure which is largely dependent on the balance between rate of production of aqueous humour, the driving force behind its generation, and the rate of drainage of spent aqueous via the trabecular network. As a consequence of its role in the generation of aqueous humour the ciliary body is the most heavily vascularised part of the eye.

An important feature of the eye is the blood-aqueous barrier which serves to prevent the entry of high molecular weight, hydrophilic substances into the aqueous from the blood.Anti-inflammatory drugs such as indomethacin (an inhibitor of prostaglandin synthesis) can ameliorate the effects of barrier breakdown to some degree. Any biomaterial designed for intraocular use must not stimulate a pronounced inflammatory response as prostaglandins generated may further compromise the barrier.

1.3.2 The Viterous Humor

Viterous Humor imparts the stability of the posterior components of the eye, attenuating the stresses imposed on the retina by sudden movement. It is essentially a gel composed of Hyaluronic Acid, Collagen and plasma proteins which is bounded by the retina, the ciliary body and the posterior capsule of the lens

1.3.3 The Lens

The lens is situated just behind the iris and the pupil and is attached to the ciliary body via the suspensory ligament (Figure2). For distant objects limited refraction needed so the cross-section of lens thinned, on the other hand for close up objects the high refraction is done by thickening of the lens. The pull of ligament causes flattening in the structure, on contrary, relaxation causes thickening. This process is called Accommodation and it is controlled by autonomic nervous system.

http://www.medicinenet.com/Script/Main/art.asp?li=MNI&ArticleKey=314

Figure 2: The Lens

The lens itself is a transparent biconvex body covered by the capsule, an outer elastic envelope. Beneath the anterior portion of the capsule as far as the equator of the lens is a single layer of lens epithelial cells. These cells give rise to non-dividing, lens fibre cells which, together with interstitial material, form the internal lens substance. The high refractive index of the lens is due to the synthesis of specialised proteins, called the crystallins, by the lens cells

The important property of the lens is there is no meaningful cell loss and the proteins have long lives in a light-saturated environment. However, lens core proteins are exposed to environmental damage over many decades. Such damage either as a result of age-related environmental insults, sudden physical trauma, radiation pulse or poor nutrition, results in opafication of the lens and the condition known as Cataract.

II. CATARACT

A cataract is a cloudiness or opacity in the normally transparent crystalline lens of the eye (Figure 3) . This cloudiness can cause a decrease in vision and may lead to eventual blindness.

Figure 3: Difference between Normal and Cataract Lens

a. Normal

b. Cataract

2.1 Causes and Symptoms of Cataract

Cataracts are the world's leading cause of blindness, accounting for approximately 42 percent of all cases of blindness in all nations. As people age, degenerative changes in the lens' proteins occur. Most cataracts develop during the normal course of aging. Proteins in the lens change and group together. Over time, the lens becomes firmer or more opaque. Although it is rare, sometimes children and infants also have cataract. The possible reasons for this kind of cataract can be: Chromosomal abnormalities, such as Down syndrome; Diabetes and other metabolic disorders; Exposure to high-voltage electricity, including lightning; Heredity; Living at high altitudes with exposure to sunlight; Premature birth; or radiation treatment around the eye etc.

The main symptoms of cataract are:

· Cloudy or blurry vision

· Double vision (diplopia)

· A sense that colors appear faded

· Seeing halos around lights

· An increased sensitivity to glare

2.2 Treatment of Cataract

The only way to cure the cataract is by surgery. There are three ways of surgery:

Intracapsular surgery. The surgeon removes the entire lens, including the capsule. This method is completely not used now.

Extracapsular surgery. This is a rather old technique in which a 12mm incision is performed in the eye to extract the lens as a whole. The lens' capsule is left in place to hold an intraocular lens. Multiple sutures are required to seal the eye after surgery. These sutures must be carefully tightened not to produce astigmatisim.

Phacoemulsification. An ultrasound or laser probe is used to break the lens apart without harming the capsule (Figure 5). These fragments are then aspirated out of the eye. A foldable intraocular lens (IOL) is then introduced through the 3mm incision. Once inside the eye, the lens unfolds to take position inside the capsule.

No sutures are needed, as the incision is self-sealing. The risk of astigmatism and sudden pressure changes inside the eye are minimized. The procedure is safe enough to be done under topical anesthesia (anesthetic eyedrops). Visual rehabilitation is extremely fast and patients don't need to suspend their everyday activities.

Figure 5: Phacoemusification Method

III. INTRAOCULAR LENSES

During cataract extraction the anterior lens capsule is opened and the contents of the capsule bag removed. To correct the loss of the refractive power of the lens IOLs are being used. There are mainly three types of IOLs present: Anterior chamber IOL which sits in front of the iris but behind the cornea, an Iris Clip Lens which straddles the pupil, and finally a Posterior Chamber IOL which sits behind the iris within or on the capsular bag, which is now the lens of choice for the correction of aphakia.

The standard IOL consists of a central

optic which is supported by haptics, projections

from the main body of the lens, which provide

support in the eye (Figure 6).

3.1 PMMA IOLs

Polymethylmethacrylate (PMMA) has been the standard IOL material since the surgical approach was first developed in 1950s. It is a minimally reactive, optically clear, rigid acrylic polymer of the methyl ester of methacrylic acid. The methylmethacrylic acid monomer from which PMMA is produced is toxic, but the polymerized molecule that appears as PMMA is inert and virtually unreactive, making it suitable for long-term implantation. PMMA is hard and durable and it remains rigid below 100°C. IOLs of PMMA can be produced by casting, lathe cutting, injection molding, and compression polymerization .

Although PMMA has this advantages the major problems still occur as a consequence of its relatively low surface energy which may result in both corneal endothelial damage on insertion and post-operative adhesion of inflammatory cells to the IOL. Besides, for the implantation of PMMA IOLs relatively larger incisions needed. Also unlike the crystalline lens, which absorbs more than 99% of ultraviolent light, pure PMMA absorbs only 3%.

The biocompatibility of IOLs are improved by process modifications to produce a highly polished surface; the generation of both soft, high-energy surfaces using NVP and HEMA and hard low-energy surfaces using perfluoropropane; and the binding of heparin and hyaluronic acid to the outer surface of the lens. The most recent coatings are of phosphorylcholine-based polymeric coatings, which were shown to reduce protein adsorption, cellular adhesion and neutrophil activation by the PMMA surface and were shown in vivo to reduce cellular deposition on to the lens.

3.2 Foldable IOLs

By the Phacoemulsification method, the lens is implanted through a 3-3.5 mm incision. This small incision has encouraged the companies to design foldable and new models of IOLs (Figure 7).

http://www.drloden.com/intraocular.html

Figure 7: Foldable Plate IOL

These foldable lenses have been manufactured from various materials such as, silicone elastomers, collagen copolymers, PHEMA hydrogels and Acrylic polymers (Table 1).

Table 1: Examples of intraocular lens materials

The importance property of the lenses is their folding and unfolding characteristics. They are implanted though a very small incision and unfold within the capsule slowly and without leaving a mark. In this respect, acrylic lenses unfold more slowly and in a controlled fashioned than silicone lenses. Besides the high refractive index of acrylic materials give rise to thinner lenses.

The recent studies have also suggested that phosphocholine-based acrylate polymers may have application in the development of novel biocompatible foldable IOLs.

3.3 Developments of Materials

Posterior Capsule Opacification

This phenomenon is attributed to the migration of lens epithelial across the posterior capsule bag. It is so called secondary cataract and leads to a considerable reduction in visual acuity and problems with glare. The treatment of PCO with a neodymium:YAG (Nd:YAG) laser capsulotomy is relatively easy but is costly in time and money for both the health care system and patients. In addition, an Nd:YAG laser capsulotomy carries a risk of complications including retinal detachment, or macular edema which are serious.

According to the comparative study between PMMA IOL and AcrySof acrylic IOL, in three years follow up 22.2% of patients using PMMA have PCO where as only 6.2% of patients using AcrySof have PCO. The relative risk was 3.6 times higherfor PMMA. According to an other comparative stucy between Hydroview hydrogel and AcrySof acrylic IOL 55.6% in the Hydroview IOL group and 3.5% in the AcrySof IOL group required a PC YAG; the risk difference was 52.0%.

It was clear from the in vivo studies that PCO occurs less often following the implantation of acrylic IOLs than other materials. This may be attributed to the physical inhibition of lens cell migration by adhesion of the posterior capsule to the IOL following implantataion.

Accomodation

Unlike the natural crystalline lens, standard IOLs provide no means of accommodation for near and far vision. In most cases the visual adjustment is achieved through the wearing of standard spectacles.

A two-piece lens system has been patented in which the distance between the two lenses is controlled by the pressure exerted by the cilary muscle on an U-shaped flange connecting the periphery of the two lenses. Relaxation of the cilary muscle causes the lens to flatten thereby changing the focal distance of the lens.

An other approach rely on the postoperative healing following surgery during which the anterior capsule remnant fuses to the posterior capsule causing fibrosis around the lens haptic on the implanted lens which leads to a rearward deflection of the lens against the posterior capsule. Accommodation is achieved through contraction and relaxation of the cilary muscle that relaxes and stretches the fused remnant causing the lens to move forwards and backwards relative to the retina thereby adjusting the focal distance.

An other approaches include the use of viscoelastic IOL implants which may be injected into the capsular bag following removal of the natural crystalline lens. The viscoelastic gel's dimensions and refractive properties are modified as the cilary muscle contracts and relaxes causing the capsular bag to either stretch or bulge, respectively.

UV Radiation

The crystalline lens is capable of absorbing almost 99% of the uv light in the 300-400 nm range, however pure PMMA can only absorb 30%. In recent developments, uv transmission can be blocked completely by the addition or chemical bonding of a chromophore to the IOL material. The chromophores are generally derivatives of benzotriazole, typically hydroxybenzophenone or hydroxybenzotriazole.

4.3 Complications of Foldable IOLs

A survey of members of the American Society of Cataract and Refractive Surgery (ASCRS) to evaluate the complications of foldable IOLs requiring explantation or secondary intervention was begun in 1998. This annual survey allows an analysis of ongoing trends related to complications of foldable IOLs, which can then be evaluated for each particular lens material and design. 4 ma’n types of explanted IOLs are compared: 3-piece monofocal silicone; 3-piece acrylic; 1-piece (plate type) silicone; 3-piece multifocal silicone.

According to this survey, 3-piece monofocal silicone IOLs were the most frequently removed or exchanged. The main reason for the removal and exchage is incorrect lens power (40%), followed by disloccation/decebtration (32%) and glare/optical abbrrations and damaged IOL during insertion (9%). This high frequency of the removal of 3-piece silicone lenses isbecause they are the most commonly implanted IOLs during the time of survey.

3-piece acrylic group is in the second place according to their removal. The main reason is again the incorrect lens power (39%). This is followed by glare/optical abbrevattions (24%) and dislocation/decentration (15%). The evidence suggests that the sharp or squared optic edge in the most commonly used 3-piece acrylic IOLs in conjunction with the high refractive index of the acrylic material may be responsible for some of these symptoms. Changes have been made to the edges of newer 1-piece acrylic IOLs as well as in more recently approved 3-piece acrylic IOLs that may help minimize symptoms of glare/optical aberrations in the future.

In the third place there is 1-piece plate-haptic silicone IOLs. Other than the previous two these lenses are removed because of disloacation/decentration frequently (50%). Plate-haptic silicone IOLs requires a well performed continuous curvilinear capsulorhexis (CCC) with intact capsule due to prevent decentration due to lack of haptic fixation within the capsule bag. The newer IOLs have a larger positioning hole, however, even with the increased use of the larger positioning hole, the incidence of decentration /dislocation remains high with these IOLs.

The number of explanted 3-piece multifocal silicone IOLs has decreased over three years. However, the main reason for the removal is because of glare/optical abbreviations (89%).

In overall the most frequent reason for the removal of foldable lenses is now the incorrect lens power. The axial length and keratometry measurements are essential and should be done carefully by the surgeon. Newer methods of measuring the axial length using laser interferometry rather than ultrasound may improve the accuracy. Secondly, a CCC followed by careful removal of all crystalline lens material and placement of foldable IOL completely within the capsular bag may help to eliminate the problems of dislocation/decentration. Lastly, IOLs should be folded, loaded, and inserted carefully to prevent cracking or tearing during loading or insertion.

IV. REFERENCES

ARTICLES

1. “Ocular biomaterials and implants”,

Biomaterials, 22 (2001) 769-785

2. “A review of the development of a synthetic corneal onlay for refractive correction”,

Biomaterials, 22 (2001) 3319–3328

3. “Complications of foldable intraocular lenses requiring explantation or secondary

intervention—2000 survey update”,

J Cataract Refract Surg, Vol 27, August 2001

4. “The Effect Of Ionizing Radiation On IntraocularLenses”,

Int. J. Radiation Oncology Biol. Phys., Vol. 51, No. 1, pp. 184–208, 2001

5. “Posterior capsule opacification and lens epithelial cell layer formation: Hydroview hydrogel versus AcrySof acrylic intraocular lenses”,