Ординатура / Офтальмология / Английские материалы / Medical Contact Lens Practice_Millis_2005

Table 5.3 Management of corneal vascularization

an altered edge lift to improve tear exchange may alleviate the situation.

Silicone hydrogel lenses may offer a viable alternative as extended-wear lenses if hypoxia is the cause of the condition, but will not necessarily solve the problem of a stagnant tear film beneath the lens. Silicone hydrogel lenses, used as dailywear lenses, are useful in cases of vascularization (Fig. 5.18).

Other causes of limbal hyperemia that should be excluded are a tight lens and a decentered rigid lens.

In all cases the care systems should be reviewed and an unpreserved system used in place of one with preservatives. Careful follow-up is essential to make sure the vessels do not recur after lens wear recommences.

PATIENT-RELATED PROBLEMS

Motivation

In all cases the reason for wanting contact lenses should be elicited to judge whether or not expectations can be met.

Busy executives are often not prepared to devote the necessary time to learning to insert and remove their lenses and often cut corners with their care regimen. The latter can be avoided by fitting 1-day lenses, although some of these are very thin and difficult for a novice to handle. Many keratoconus patients find difficulty in adapting to rigid lenses and the reason for choosing these lenses needs to be carefully explained.

Young children are sometimes encouraged to wear contact lenses by their parents who are anxious for their offspring not to wear spectacles

(A)

(B)

Figure 5.18 A: Vascularization of the cornea.

B: Improvement when changed to silicone hydrogel lens.

because they fear this might make them vulnera ble to teasing. It is the author’s practice not to fi children unless the child is enthusiastic to hav lenses or there is a medical reason for the lenses Parents usually understand when it is explained that a traumatic episode attempting to inser lenses in an unwilling child may well delay len wear. The objective can be achieved more rapidly if the child is given literature to read, and th process of fitting and caring for the lenses i explained. The parents are advised to make an appointment in 6 or so months when the child ha had time to consider. Many children are happie if, from the start, they are allowed to inser the lenses themselves rather than if the lense are inserted by the practitioner. This means tha

sufficient time must be allowed to teach the patient at the initial visit.

In all but the youngest children, the pros and cons should be explained in simple language to the child (whose wishes should always be taken into consideration), together with a more detailed explanation for the parents. If a lens is needed for medical reasons it is essential to explain this to the child. Most children are capable of understanding that without the lens they may not see well and that this may affect them when they are older, for instance they may not be able to drive or take up a job they want. Children are sensitive and do not like to be excluded from the discussion.

Noncompliance

Patients fail to:

●clean their lenses

●use a rub and rinse step

●change their disinfecting solutions daily

●change their cases regularly. In addition they:

●wear lenses for longer than they should

●may wear inappropriate lenses overnight and increase the risk of microbial keratitis.

It is inadvisable to wear lenses while swimming, but many lens wearers do, particularly if they have high refractive errors, and they fail to heed the advice that lenses should not be worn if the eye is red, painful, photophobic or has reduced vision.

The clinician should ensure that the instructions for wearing and caring for the lenses are explained fully by a trained member of staff at the initial teaching session, and that this is reinforced at follow-up visits by reviewing the patient’s regimen and pointing out where it is inadequate. If a particular care system is proving difficult a change should be made to an alternative simpler regimen. If patients are already contact lens wearers the instructions they have received previously should be reviewed and any necessary adjustments made.

Contact lens acute red eye

The contact lens acute red eye (CLARE) syndrome is associated with soft lens extended wear and

causes a painful red eye, which wakes the patient (see Fig. 7.3). There is corneal swelling and stagnation of the tear film beneath the lens, under the closed eyelid. Contaminated lenses and cases have been implicated in some instances and, in particular, infection by Pseudomonas and Serratia spp.22

Poor blinking

Many people “flick” blink, that is they do not completely close their eyes and so fail to rewet their lenses adequately. Patients can be taught to close their eyes gently and completely as in sleep. These exercises are particularly useful in those with reduced tear film and VDU users.

AVOIDING COMPLICATIONS

Most patients can be fitted with lenses if they and the practitioner are prepared to invest sufficient time. The patient’s work, lifestyle and hobbies must be taken into account when selecting a suitable lens and care system, and the reasons for making particular choices should be fully explained.

Both practitioners and patients should wash their hands before handling lenses. Watch the patient when they are inserting or removing lenses because they often hold them under running tap water, lick their fingers before touching the lens, or lick an RGP lens.

Aftercare visits should record the recent history and the eye should be examined fully. Check that patients are using the lenses and solutions prescribed, and if they are not discuss the reasons for this. Patients should be encouraged to bring their solutions with them to the consultation because many cannot remember which they are using.

All contact lens cases should be examined at each visit because they are often filthy, even though many solution manufacturers now include a new case with each new bottle. This may be because the patient has not bothered to change the case, or prefers an older, and often obsolete, design.

Ensure that vision with the lenses is adequate and assess the fit. Consider whether or not it could be improved, or whether one of the many new developments might solve a problem. It is

important to ensure that the patient has spectacles with an up to date prescription so that they are adequate for use in an emergency.

Complications are most likely to arise with larger lenses and longer wearing times. Despite

the potential for problems with contact lens wea most complications do not cause lasting damag and the risks can be minimized by taking the tim to explain how they may be avoided.

1.Begley CG, Barr JT, Edrington TB, et al. Characteristics of corneal staining in hydrogel contact lens wearers. Optom Vis Sci 1996;73:193–200.

2.Itoi M, Kim O, Kimura T, et al. Effect of sodium hyaluronate ophthalmic solution on peripheral staining of rigid contact lens wearers. CLAO J 1995;21:261–267.

3.Schnider CM, Terry RL, Holden BA. Effect of lens design on peripheral corneal desiccation. J Am Optom Assoc 1997;68:163–170, 242–245.

4.Schnider CM, Terry RL, Holden BA. Effect of patient and lens performance characteristics on peripheral corneal desiccation. J Am Optom Assoc 1996; 67:144–150.

5.Little SA, Bruce AS. Role of the post-lens tear film in the mechanism of inferior arcuate staining with ultra-thin hydrogel lenses. CLAO J 1995;21:175–181.

6.Little SA, Bruce AS. Environmental influences on hydrogel lens dehydration and the post lens tear film. Int Contact Lens Clin 1995; 22:148–155.

7.Goldberg EP, Bhatia S, Enns JB. Hydrogel contact lens–corneal interactions: a new mechanism for deposit formation and corneal injury. CLAO J 1997;23:243–248.

8.Efron N, Veys J. Defects in disposable contact lenses can compromise ocular integrity. Int Contact Lens Clin 1992;19:8–18.

9.Tripathi RG, Tripathi BJ. Lens spoilage. In: Contact Lenses: The CLAO Guide to Basic Science and Clinical Practice, ed. Dabezies OH Jr, pp 45.1–45.33. Boston: Little Brown;1984.

10.Hart DE, DePaolis M, Ratner BD, Mateo NB. Surface analysis of hydrogel contact lenses by ESCA. CLAO J 1993;19:169–173.

11.Hart DE. Contact lens/tear film interactions: depositions and coatings. In: The CLAO Guide to Basic Science and Clinical Practice, eds Dabezies OH Jr, Ilhan B, pp 45A.1–45A.27. Boston: Little Brown;1990.

12.Jones LWJ. A review of techniques for analysing hydrogel lens deposition. Trans of the BCLA, Annual Clinical Conference, pp 36–40. 1990.

13.Minarik L, Rapp J. Protein deposits on individual hydrophilic contact lenses: effects of water and ionicity. CLAO J 1989;15:185–188.

14.Jones L, Evans K, Sariri R, et al. Lipid and protein deposition of N-vinyl pyrrolidone-containing Group II and Group IV frequent replacement contact lenses. CLAO J 1997;23:122–126.

15.Ilhan B, Irkec M, Orhan M, Celik H. Surface deposits on frequent replacement and conventional daily wear soft contact lenses: a scanning electron microscope study. CLAO J 1998;24:232–235.

16.Jones L, Franklin V, Sariri R, Tighe B. Spoilation and clinical performance of monthly vs three monthly Group II disposable lenses. Optom Vis Sci 1996; 73:16–21.

17.Guillon M, McGrogan L, Guillon J-P, et al. Effect of material ionicity on the performance of daily disposable contact lenses. Contact Lens and Anterior Eye 1997;20:3–8.

18.Alongi S, Rolando M, Colonna A, et al. Bacterial load and protein deposits on 15-day versus 1-day disposable hydrophilic contact lenses. Cornea 1998;17:146–151.

19.Hart DE, Plociniak MP, Grimes GW. Defining the physiologically normal coating and pathological deposit: an analysis of sulfur-containing moieties an pellicle thickness on hydrogel contact lenses. CLAO J 1998;24:85–101.

20.Sweeney DF. Corneal exhaustion syndrome with long-term wear of contact lenses. Optom Vis Sci 1992;69:601–608.

21.Boyce P, Carman SK. A method to quantify vascularisation. Int Contact Lens Clin 1998;25:77–84.

22.Holden BA, La Hood D, Grant T, et al. Gramnegative bacteria can induce contact lens related acute red eye (CLARE) responses. CLAO J 1996;22(1):47–52.

Most complications of contact lens wear, with th exception of polymegethism, resolve withou permanent sequlae when lens wear ceases. How ever, microbial keratitis is a potentially sight threatening condition of the cornea characterize by epithelial ulceration and stromal infiltration. I can result in corneal scarring or even perfora tion,1,2 and contact lenses have come to be recog nized as a major cause of microbial keratitis.3

Contact lens-related microbial keratitis (CLRMK is most often due to infection with Pseudomona aeruginosa, Staphylococcus aureus or Streptococcu pneumoniae. Rarely, it is due to infection by fungi an Acanthamoeba spp. Most cases of infection b Acanthamoeba spp. are associated with contact lenses

It is generally accepted that for infection t occur there must be an epithelial defect as well a pathogenic organisms.

PRINCIPLES OF OCULAR SURFACE PROTECTION

The eye is constantly exposed to bacteria, bu infection rarely develops. This is because protec tive mechanisms remove or kill most organism before infection occurs. These mechanisms includ the immune mechanisms, which may be nonspe cific (natural or innate) or specific (adaptive o acquired). They are designed to protect the bod from damage by microorganisms.

Nonspecific immunity

Nonspecific (innate) immunity is a response tha is not specific for a particular organism. Als

the response does not increase with repeated exposure.

Nonspecific immunity includes mechanical as well as physiological means of preventing infection. It is conferred by intact, strong, physical barriers such as skin, epithelium and basement membranes. In the eye it includes:

●the eyelashes and blink reflex, which prevent many foreign bodies from entering the eye

●blinking, which reduces adherence of organisms to the cornea

●tear flow, which washes organisms and debris from the eye.

The tears contain enzymes and antibodies, and cells that can ingest and kill organisms, so preventing bacteria from living on the surface of the eye.

Mucin provides a physical layer of protection for the cornea and prevents bacteria binding to the corneal cell surface, the integrity of which is maintained by tight junctions.

Sloughing of surface epithelial cells from intact epithelium removes any microorganisms that have managed to gain entry or become adherent to the cell because these organisms will be lost at the same time.

When the cornea is injured bacteria gain entry to deeper cells and are not removed by sloughing, and it is easier for the organisms to avoid host defenses and immune factors, but they create an inflammatory response.

An immediate defense against foreign organisms is provided by cytotoxic natural killer cells and macrophages (phagocytes that ingest and destroy foreign material). These mechanisms do not rely on specific recognition or memory. Lysozyme is an enzyme secreted by macrophages that causes the deaths of organisms by breaking the peptidoglycan bonds in the bacterial cell wall. Lactoferrin enhances the activity of natural killer cells.

The conjunctival mucosa secretes an adhesive coating of mucus, which traps bacteria and other foreign bodies. The normal bacterial flora obstructs the growth of pathogens by competing for nutrients.

Nonspecific immunity protects the eye by:

●engulfing foreign material (phagocytosis)

●killing infectious organisms (cytotoxicity)

●causing an inflammatory reaction at the site of the infection.

Specific immunity

Specific immunity differs from nonspecific immunity in that it is specific for a particular antigen and has memory that results in an enhanced response on further contact with that antigen.

An antigen is any molecule that is recognized by the immune system and results in the formation of antibodies. Antigens, such as bacteria, may be introduced into the host, or they may be formed within the host, for example bacterial toxins.

In specific immunity an immunocompetent cell encounters an antigen, which it recognizes, and this results in sensitization and the production of antibodies (immunoglobulins). Alternatively the cells mature into immunocompetent effector cells, and antibodies and cells act to eliminate the antigen.

Cells of the immune response

Small lymphocytes are the key cells of the immune response. They are white blood cells that can recognize “foreign” material as different from “self” by means of antigen receptor molecules on the cell surface. There are two types:

●B cells (B lymphocytes), which mature after contact with antigen into antibody-secreting cells

●T cells (T lymphocytes), which regulate the immune response, help B cells make antibody, destroy virus-infected cells and cause phagocytes to destroy pathogens they have ingested.

Bcells

Bcells develop in the bone marrow and divide

and differentiate into plasma cells, which form antibodies (immunoglobulins [Igs]). Antibodies can be secreted into the tissue fluid to be complexed with antigen, or they are bound to the B cell as an antigen receptor.

Antibodies bind antigen and interact with host tissues to remove antigen. There are five classes of Ig:

●IgG is the major serum immunoglobulin and the main long-term antibody produced in response to most antigens

●IgA occurs as monomers, dimers and polymers of the basic unit and is the main ocular antibody – secretory IgA is dimeric (i.e. it consists of two units and a joining [J] chain) and is most common in secretions, including in the ocular surface, where it protects mucous membranes by preventing the adherence of microbes

●IgM acts in primary immune responses, and an early peak is seen after antigen exposure.

●IgE binds to mast cells and basophils and causes them to release chemical mediators after contact with antigen – these chemical mediators are agents such as histamine, which causes itch, vasodilation, and leakage of fluid out of vessels to produce edema, and is important in allergic reactions, including asthma and hay fever

●IgD, which at present has an unknown role.

T cells are required to initiate antibody production against many antigens.

Tcells

Tcells are derived from cells in the bone marrow

and migrate to the thymus gland where they are developed into immunocompetent cells. They have T-cell antigen receptors (TCRs) and differentiate into two “cluster differentiated (CD)” types, one characterized by the CD4 marker and the other by CD8.

T cells recognize antigen formed within the host’s cells and attack cell surface antigens. There are several other subclasses of T cells:

●cytotoxic T cells (Tc) can destroy cells infected by virus and are usually CD8 cells

●most helper T cells (Th) are CD4 and contain cytokines, which act as messengers between cells, and as inflammatory mediators, which can amplify the immune response – they help B cells differentiate into plasma cells to form antibody, and they are active against extracellular antigens.

Phagocytes

Phagocytes (Greek: phagein – to eat, kytos – cell) include blood monocytes, macrophages (big eaters) and polymorphonuclear leukocytes (neutrophils [PMNs]).

Particles, including microbes, cell debris an antigens attach to the cell membrane of the phago cyte, which then extends pseudopodia around th particle and engulfs it into the cell.

Lysosomes are specialized structures in all cell that contain enzymes. In macrophages thes enzymes damage and digest the phagocytose elements, which are then released back into th tissues.

Monocytes are cells that circulate in the blood but can migrate into the tissues and turn int macrophages. They engulf and digest cell debri and foreign material, and participate in the pres entation of partially degraded antibody–antige complexes or free antigen to T and B cells.

Polymorphonuclear leukocytes are the larges group of white blood cells and include the phago cytic cells that migrate into the tissues in respons to chemotactic stimuli. They are characteristic o acute inflammation.

Other cellular elements

Eosinophils can damage some pathogens an control inflammation, and are present in allergi disease.

Basophils, mast cells and platelets contai inflammatory mediators such as histamine, an link the immune responses to the inflammator reaction. Basophils circulate in the blood, and mas cells are present in mucosal surfaces, and skin.

Antigen-presenting cells are cells that presen antigen to B and T cells so that the B and T cell can respond to it.

Although specific and nonspecific immunit are described as two separate entities there i a considerable interaction between the tw systems.

The mucosa-associated lymphoid tissu (MALT)4 is an immune defense system that i independent of systemic immunity. It involve mucosal areas in the body as well as the eye These produce antigen-stimulated B cells, whic travel via lymphatic vessels and reach the systemi circulation and the lacrimal gland, where the clonally expand, and differentiate into immun oglobulin A (IgA) plasma cells. The plasma cell synthesize dimeric IgA beneath the surfac epithelium of the gland and this is bound to

secretory component formed by the acinar cells. This complex is then transported across the cytoplasm and secreted into the lacrimal ducts and enters the tears. IgA is the major immunoglobulin of the external eye and covers the conjunctiva. It prevents bacterial attachment and reduces antigen absorption.5,6 It remains effective because it is not affected by ocular proteolytic enzymes.

Normal flora of the conjunctival sac maintain a balance in the environment and may have an inhibitory effect on the survival of pathogens,7,8 possibly by competing for nutrients.

Despite all the protective mechanisms present, it is thought that the most important factor in the prevention of infection is an intact corneal epithelium. Recent work,9 has shown that some strains of Pseudomonas are cytotoxic and can injure the intact corneal surface in vitro by disrupting the corneal cell membrane, and this raises the possibility that an intact epithelium may not be a barrier under all circumstances.

Corneal epithelial cells produce antibacterial substances (defensins) when they come into contact with an organism, and this may explain why bacteria do not approach the apical cell surface, there are few organisms in tears, and infection is rare. Those that are present may be transient contaminants from the skin.

ETIOLOGY

The etiology of CLRMK is summarized in Table 6.1.

Alterations in the cornea

Epithelial changes

Changes in the epithelium have been associated with all types of contact lens wear. These include a reduction in microvilli and altered cell shape,10 disruption of tight junctions, and dilation of the intercellular spaces.11 There is an increase in the permeability of the epithelium, which has been reported with hard lenses, and thinning of the cornea due to epithelial cell loss associated with soft lenses. Epithelial microcysts have been found with all types of lens, but are seen most commonly with extended-wear soft lenses and result from hypoxia. Preservatives in solutions may be toxic

Table 6.1 Etiology of contact lens-related microbial keratitis

Etiologic factor

Altered cornea (epithelium, stroma and endothelium) Trauma

Hypoxia

Reduced corneal sensation

to the epithelium and can cause areas of punctate staining, which may become confluent.

Corneal abrasions may be caused by difficulty or carelessness when inserting or removing the lens particularly in those such as the elderly and diabetics, who may have reduced sensation in their fingers, and in those with long fingernails. It is often possible to see small areas of superficial stain at the six o’clock position in those who have just removed a soft lens, and central splits in a soft lens may also cause epithelial cell loss as the split opens and closes with the blink.

It is surprising how little trauma may result from peripheral damage of an RGP lens, although the patient may be aware of some discomfort. It is usually possible to permit the patient to continue to wear the affected lens, provided it does not cause an abrasion or discomfort, until a replacement lens has been obtained.

Stromal changes

Contact lenses may cause some degree of stromal edema, which is least with RGP daily-wear lenses and greatest with soft extended-wear lenses.

Effect of contact lenses on the endothelium

Three changes have been reported in the endothelium,12,13 namely:

●blebs

●polymegethism

●bedewing.

In the posterior endothelium blebs are transitory swellings that resolve after 30 minutes, and bedewing is thought to be clusters of inflammatory cells on the posterior endothelial surface, possibly due to a

mild uveitis associated with contact lens wear, that resolve rapidly once lens wear ceases. Polymegethism is a variation in cell size that appears to be irreversible, but does not cause clinical symptoms. It is best viewed with the specular microscope.

Hypoxia

The eye obtains oxygen from the atmosphere via the tear film, the aqueous and the limbal blood vessels. With the eye open the oxygen tension in the tears is 20.7 kPa (155 mmHg), but this falls to 7.3 kPa (55 mmHg) when the eye is closed. These figures are further reduced when a contact lens, particularly a soft lens, is worn on the closed eye. It has been estimated that the minimum oxygen transmissibility to prevent corneal edema in extended wear is 75 10 9 which is equivalent to an oxygen tension of 5.3 kPa (40 mmHg).14

The contact lens acts as a barrier to the transmission of oxygen to and the removal of carbon dioxide from the cornea and results in a build up of lactic acid that may cause edema. Tear film stagnates beneath lenses if there is an insufficient tear pump effect, which is minimal with soft contact lenses and with lenses that are worn overnight because of the lack of the blink.

Reduced corneal sensation

Corneal sensation is reduced in contact lens wear and this reduction is greater with PMMA and lowDk RGP lenses than with soft lenses, and takes longer to return to normal when lens wear ceases. Reduced sensation also occurs in diabetics, in trigeminal nerve (cranial nerve V) palsy, and following intraocular surgery. Postoperative hypoesthesia recovers in the weeks following surgery and may make fitting easier in the early postoperative weeks.

RISK FACTORS

The risk factors for CLRMK are summarized in Table 6.2.

Contact lenses

Contact lenses are the commonest cause of new cases of microbial keratitis.3 Soft lenses,

Table 6.2 Risk factors for contact lens-related microbial keratitis

Contact lenses

Dry eye

Lens solutions

Immunosuppression

Tap water

Diabetes mellitus

Corneal exposure

Topical corticosteroids

Smoking

particularly if used on an extended-wear basi carry a significantly higher risk compared to rigid lenses.15 Studies have suggested an annual inci dence of 1 in 450 for extended-wear soft lense and 1 in 2500 for daily-wear soft lenses.16

The risk of ulcerative keratitis is 10–15 time greater for conventional extended-wear than fo daily-wear soft lenses. “Disposable lenses” hav been reported as being a greater risk than conven tional daily soft lenses.17 The term “disposable has been used to refer to the use of lenses used fo overnight wear and “disposed” of after 1 week but should be restricted to those lenses worn fo 1 day and then discarded. Longer periods of wea should be referred to as “frequent lens replacement and lenses worn overnight should be termed “extended-wear”.

It was expected that the new generation o extended-wear, silicone hydrogel lenses, which transmit more oxygen, would reduce the risk o infection. Despite their high oxygen transmission recent reports18,19 demonstrate that the risk o CLRMK has not been eliminated, although they suggest that the incidence of CLRMK with silicon hydrogel lenses may be lower than with low-Dk soft lenses used for extended wear.

These risks show that infection is fortunately not common and only a large practice is likely t see it. In the UK many patients with CLRMK pres ent to the accident and emergency departments o their local hospital rather than to the prescribing practice. Nevertheless the consequences of infec tion are such that all clinicians need to be aware o the potential risks.

Solutions

Cases of CLRMK have been associated with inadequate care regimens and when there has been failure to comply with the care instructions. Nevertheless compliance seems to be less important in some cases of bacterial keratitis where patients, who have shown good compliance have still suffered infection.20 Acanthamoeba infection is best avoided by adhering to the recommended care regimen (see below).

Solutions may become contaminated with use (each squeeze of the bottle resulting in an intake of nonsterile air), by leaving bottles open and by contaminating the opening with hands that are not clean. Although the solutions have disinfectant activity, this gradually declines with the increased bacterial load until it is no longer effective. Patients need to understand the need to cap bottles and the rationale for discarding old solutions. Practitioners should also ensure that all clinic staff understand the need to recap all bottles immediately after use.

The problem of getting patients to clean and disinfect their lenses adequately and to maintain the regimen over years has not been solved, but regimens have been simplified in an attempt to improve compliance. Meanwhile it is important that time and effort is spent on educating the patient. Good compliance is more likely when patients understand the reason for cleaning and disinfecting their lenses.

Other factors

Eyelid abnormalities, such as a facial nerve (cranial nerve VII) palsy and lagophthalmos, which result in corneal exposure because of an inability to close the eyelids, result in a greater risk of corneal damage and infection. Ectropion and a blocked nasolacrimal duct cause the formation of a stagnant pool of tear fluid in the lower fornix that easily becomes infected and may give rise to corneal infection if an abrasion occurs.

A very dry eye, such as is seen in Sjögren’s disease or Stevens–Johnson syndrome, causes abnormalities of the epithelium and there is a failure to wash away debris and bacteria from the surface of the eye.

Immunosuppressed patients on systemic corticosteroids, and those who have AIDS, carry a higher risk of infection, as do diabetics, those on topical corticosteroids and smokers, in whom it is thought that smoking may contribute to a relative hypoxia.21 These conditions make the wearing of a contact lens more risky.

PATHOGENICITY AND TISSUE DAMAGE

Pathogenesis is determined by three factors:

●virulence of the organism causing the infection

●host response

●anatomic features of the site of infection.

Water

Water, particularly tap water, has been implicated in Acanthamoeba infection, both when it has been used to wash and rinse rigid lenses and when it has contaminated soft lenses that have been worn in the jacuzzi (hot tub) or when swimming.

In the USA, Acanthamoeba infection was associated with homemade saline using salt tablets and distilled water, neither of which is sterile. Now that homemade saline is no longer used the incidence of Acanthamoeba keratitis has fallen in the USA.

In the UK the use of chlorine disinfecting systems, which are ineffective against Acanthamoeba spp, and the use of tap water for rinsing lenses and cases, have been implicated in Acanthamoeba keratitis.

Virulence

The virulence of an organism is dependent on its ability to invade tissue, resist the host mechanisms and produce tissue damage.

Invasion

Pathogens from contaminated contact lenses, foreign bodies or solutions are found in the tear film and can invade the cornea following minor trauma. Recently Fleiszig et al.9 found evidence in vitro that certain strains of Pseudomonas could penetrate the intact epithelium, but this took 2 hours to occur, and may explain why it does not cause problems in vivo unless there is injury or a contact lens is worn.

Bacteria adhere to corneal epithelium by means of adhesive protein molecules (adhesins) on their surface, which attach to receptors on the host epithelial cell. Some organisms adhere more readily to ulcerated epithelium than others, including

Staphylococcus aureus, Streptococcus pneumoniae and

Pseudomonas aeruginosa, which are those organisms most often associated with CLRMK.2 Adhesion of P. aeruginosa is facilitated by the presence of numerous hair-like structures (pili) on the surface of the bacteria and by its ability to secrete and surround itself with biofilm in response to adverse environmental conditions.

Once adherence to the corneal epithelium has occurred the cell walls of the bacterium and the epithelial cell fuse, and the bacteria are engulfed by the cell. The inclusion of bacteria may be part of the ocular defense system as the cells slough off. When the cornea is injured, bacteria gain entry to deeper cells where they can avoid most antibiotics and immune factors, but create inflammation.

Enzymes produced by the bacteria including proteases, leukocidin and hemolysins, aid in the destruction of the cornea and assist penetration into the stroma where bacteria multiply, producing toxins, which diffuse into the surrounding tissue.

Invasion occurs rapidly, and Dart and Seal found, experimentally in an animal model, that an inoculum of P. aeruginosa had disappeared from the surface of corneal epithelium within 4 hours, and invasion of traumatized epithelial cells occurred after 7.5 minutes.22

Bacteria also adhere to new and worn contact lenses and are found in higher numbers adhering to unworn nonionic lenses compared to ionic lenses. Those organisms with greater surface hydrophobicity adhere in greater numbers than less hydrophobic organisms. There does not appear to be any preferential adherence to lathing marks or surface defects.23 Bacteria adherent to a lens are held in close proximity to the eye for considerable periods of time, depending on the mode of wear, and this increases the opportunity to cause infection.

Resistance to host defense mechanisms

Bacterial biofilm exists on surfaces such as contact lenses or lens cases. It consists of microorganisms

organized within an exopolymer matrix (glycoca lyx), which is secreted by the bacteria in respons to an adverse environment. Bacteria eventuall become irreversibly bound to the lens or lens case The biofilm allows the passage of gases and nutri ents, but protects the organism from phagocytosis bacterial viruses (bacteriophages) and the actio of disinfectant solutions. Bacteria in biofilm hav been shown to be 20–1000 times less sensitive t antibiotics than planktonic organisms.24

Within the biofilm, which may contain mor than one type of organism, daughter cells ma form and are released to become free floatin (planktonic) organisms in the solution or the may attach to the lens in the case.25

Currently contact lens solutions are tested onl against planktonic organisms, and many are inef fective against sessile (adherent) organisms i biofilm, with the exception of hydrogen peroxid systems, and manufacturers are not required t test for activity against Acanthamoeba spp. Ai drying of the case for 10 hours reduces the surviv ing organisms, but does not kill all the bacteria and a seed inoculum may persist.26

Tissue damage

Following invasion, bacterial toxins and enzyme are produced, which cause corneal necrosis an sloughing. Exotoxins are secreted by activel multiplying organisms, such as staphyloccoci an streptococci. In contrast endotoxins are release from Gram negative organisms only after thei death, and so they continue to cause damage afte the elimination of the pathogen. Pseudomona aeruginosa produces endotoxin and also exotoxi A27, which is secreted in a form that is highl toxic.27 It inhibits protein synthesis in the hos cells and reduces phagocytosis.

Proteases are enzymes that break down pro teins. They can degrade immunoglobulins an cause the dispersal of collagen fibrils by degrad ing proteoglycans. Leukocidin is toxic for PMNs A deep ulcer surrounded by infiltrate form where there is extensive necrosis and sloughing White cells migrate into the anterior chamber an may cause a hypopyon. Further necrosis cause greater destruction of collagen and may result i stromal thinning and even corneal perforation.