Ординатура / Офтальмология / Английские материалы / Medical Contact Lens Practice_Millis_2005

Figure 13.2 Reis–Buckler’s corneal dystrophy.

If recurrences continue phototherapeutic keratectomy3 may be considered.

Persistent epithelial defects

Persistent epithelial defects (PEDs) may be due to an abnormality of the epithelium, stem cells or surface environment of the eye.4 It is often due to a combination of these factors.

Chemical burns may result in a PED. Alkali burns have a worse prognosis than acid burns because the alkali rapidly penetrates the tissues. A TCL can reduce damage to the cornea and tissue loss due to collagenase.

Initially patients require cycloplegics, antibiotics and a pad. If there is no improvement a TCL can be applied. This may be a conventional highwater content soft lens or a silicone hydrogel lens. These are fitted with minimal movement to reduce corneal trauma. If there is little or no improvement after two months an amniotic membrane or limbal stem cell graft should be considered.

Bilateral corneal abrasions

Therapeutic contact lenses may be fitted to maintain vision when injury has affected both corneas instead of padding both eyes.

as damage to the trigeminal (cranial nerve V) o facial (cranial nerve VII) nerves and trauma due t eyelid deformities and eyelash abnormalities and from environmental conditions such as dust.

Cranial nerve palsy

If exposure keratitis from a nerve palsy is likely t be temporary, a thin, low-water content lens may be used.

If the condition persists it may be preferable to fi a scleral lens. With any type of lens the patient mus be closely supervised because the risk of infection i high. If there is little or no improvement, the uppe eyelid may be lowered, by inserting a gold weight or a lateral tarsorrhaphy may be performed.

Eyelid deformities, which can result in ocula trauma, include ectropion, entropion and scarring from injury or trachoma.

In very dusty environments a large hydrogel len will protect the eye from recurrent minor damage which assumes a greater importance in a dry eye.

Hydration

In dry eye disease such as ocular pemphigoid and Stevens–Johnson syndrome, and in chemical burns hydrogel lenses can be used, with copious lubrica tion, to protect the ocular surface. Large, thin medium-water content lenses are better than thin or high-water content lenses and patients must b seen frequently because of the risk of vasculariza tion in these very dry eyes. Silicone hydroge lenses are low-water content lenses with high oxy gen transmission and will absorb less tear film but may be less comfortable because they do no wet well despite their special surfaces.

Other means of improving hydration should b considered including punctal occlusion and envi ronmental humidification with advice to avoid drying conditions such as car heaters and air con ditioning as much as possible.

In all cases contact lenses increase the risk o infection and are fitted with extreme care.

Therapeutic contact lenses are used to protect the eye from desiccation due to exposure in cases such

Therapeutic contact lenses are used to protec the donor epithelium and to maintain hydration

following limbal stem cell and amniotic membrane grafting, or over corneal glue. They may also be used for patients who have had penetrating keratoplasty, lamellar keratoplasty and keratectomy. It is important to ensure that all sutures, when present, are intact and buried, because bacteria may track along the path of a loose or broken suture and cause intraocular infection. Very large high-water content lenses may be fitted over a trabeculectomy bleb to treat leaks. The use of prophylactic antibiotics should be considered in these cases.

MOLDING AND SPLINTING

Maintenance of fornices

In conditions such as ocular pemphigoid adhesions may form between the tarsal and global conjunctiva, which causes distortion of the eyelids, obliteration of the fornices and exposure of the globe. A large soft lens, or a scleral lens will, with the aid of lubricants, help to maintain the fornices.

Ptosis

A TCL may be used to improve a ptosis if surgery is not contemplated. Scleral lenses may be made with either a raised ledge for supporting the eyelid, or a horizontal slot in which the eyelid can rest. These lenses are now available in gas-permeable materials.

transport into the cornea depends on the physical properties of both the drug and the lens polymer, and the lens thickness. Soaking the lens in the drug before insertion results in an enhanced effect, and these lenses have been used in conjunction with topical application of the drug.

LENS SELECTION

Hydrogel lenses

Ultrathin low-water content lenses are the lenses of choice where the corneal surface is relatively regular, as in map-dot-fingerprint dystrophy or Thygeson’s.

High-water content, thicker lenses are preferred for an irregular cornea such as that found in bullous keratopathy.

Lenses should be fitted loose on normal epithelium, particularly on a dry eye, or the lens may tighten with dehydration, but a lens must be fitted with minimal movement in conditions with a loose epithelium to promote healing.

Lenses should be at least 15.5 mm in diameter and in some cases may need to be as large as 20 mm when fitting over a trabeculectomy bleb.

Conventional lenses tend to accumulate deposits that cause irritation, inflammation and papillary conjunctivitis. Disposable lenses have been used successfully as TCLs,6,7 but some problems have been encountered with very thin lenses.8

Lacerations and perforations

Corneal perforations and small lacerations that do not involve prolapsed uveal tissue may benefit from a TCL, which will seal a wound leak. A thicker steeper lens will provide a relatively tight fit that will help appose the wound margins, which swell, causing closure of the wound and reformation of the anterior chamber. In some cases cyanoacrylate glue is used to plug the wound and a lens is applied over the glue to minimize discomfort and prevent the glue being dislodged.

Silicone hydrogel lenses

Silicone hydrogel lenses with their high oxygen transmission would appear to have a useful function as TCLs now that they have been used as therapeutic lenses for periods of up to three months wear. In a study in which the lenses were replaced monthly, Lim et al.9 used them successfully in a variety of conditions, and concluded that they performed better than other TCLs used in their clinic, and they appeared safe and effective.

Rigid gas-permeable lenses

DRUG DELIVERY

Contact lenses have been considered a suitable method of delivery for water-soluble drugs.5 The

Rigid gas-permeable lenses have been used in postpenetrating keratoplasty to reduce irregular astigmatism.10 The corneas were found to remain

stable without significant warpage. A relatively flat, loose fit is advised to prevent wound dehiscence and difficulty with removal. The advent of reverse geometry lenses, which have a relatively oblate shape, has facilitated fitting these patients, and are suitable for use after refractive surgery for myopia.

Scleral lenses

Scleral lenses are useful in treating corneal disease (see p. 122) and are now made in gas-permeable materials, using preformed lenses, in sealed designs, which increase their wearing time.

Silicone rubber lenses

Silicone rubber lenses have very high oxygen transmissibility, but do not wet well. They can be very useful in chemical burns, but the diameters are limited and they are not helpful when large lenses are needed. The poor wettability means that they tend to collect deposits and patients often find them difficult to handle; they are particularly difficult to remove. In my experience they are best used while the patient is an inpatient or if the patient can attend very frequently, when the lens can be removed with sterile forceps. They are no longer available in the UK.

Collagen shields

Contact lenses made of porcine collagen, which dissolves over a period of one–three days, have been used as TCLs.11 They are translucent, not transparent, and so limit vision, and problems have been encountered when dissolution has been slow or incomplete. Tight lens syndrome, due to dehydration, has been reported12 when a collagen shield has been used in a dry eye.

Collagen lenses that have been pre-soaked in antibiotics have been used in the treatment of corneal disease, but aqueous concentration of the drug is not always adequate.13

Collagen shields are no longer available in the UK.

FIT TING THERAPEUTIC CONTACT LENSES

Great care must be taken to avoid contaminating the lens, particularly the back surface. Hands

should be washed and carefully dried on a lint free towel before inserting the lens. All effort should be made to prevent the posterior lens sur face from touching the patient’s face or eyelashe to prevent microorganisms and foreign bodie being carried onto the eye.

The use of topical anesthetic is best avoided so that that any discomfort may be recognized but in cases of severe blepharospasm a short acting, unpreserved, anesthetic such as Minims Benoxinate (Chauvin) may be used. The patient i advised to minimize the risk of foreign bodie entering the eye during the 10–15 minutes it i effective.

MANAGEMENT OF THERAPEUTIC CONTACT LENS WEAR

Although some patients use their TCLs on daily-wear basis, and need to maintain them with daily cleaning and disinfection, many wear thei lenses as extended-wear lenses. For those patient removing their lenses daily it is my opinion tha separate cleaning and disinfecting solutions ar preferred to multipurpose solutions, and that afte cleaning with a surfactant cleaner, an overnigh soak in 3% hydrogen peroxide with neutraliza tion the following morning gives the greates protection.

All patients should have access to 24-hour emer gency care. They should receive written instruc tions regarding the wearing of the lens and thos with extended-wear lenses should be provided with a bottle of lens disinfecting solution and a len case into which the lens can be placed in the even of the lens being dislodged from the eye. Thi acts simply as a suitable vehicle for temporary storage to prevent the lens drying and the patien placing the lens in tap water if suitable solution and containers are not provided. The lens should be returned to the practitioner for cleaning and sterilization (autoclaving), or replacement. Th patient must understand that the lens should no be reinserted in the eye before it has been fully sterilized.

Patients should be selected carefully; many o the patients are elderly and find the thought o lens wear daunting.

CONTRAINDICATIONS TO THERAPEUTIC CONTACT LENS WEAR

Contraindications to TCL wear include:

●active microbial infection

●poor hygiene

●difficulty in attending for follow up.

Diabetes mellitus, dry eye and anesthetic cornea are all greater risks and may be considered relative contraindications that require the risk–benefit to be carefully considered.

Patients should be reviewed 24 hours after the lens has been fitted, to ensure it has not tightened on the eye, and then at one week and one month after fitting, and three monthly thereafter. If the patient fails to attend they should be contacted to explain the importance of the visit and a new appointment made for the near future.

Lenses should be changed every 3 months or sooner if necessary. Some ophthalmologists prefer the patient to use prophylactic antibiotics and, where possible, these should be unpreserved.

Two lenses per eye should be ordered if the patient wears a conventional lens for extended wear so that one can be sent for cleaning and sterilizing without interrupting wear. This problem is easily resolved with the use of disposable lenses when new lenses should either be in the patient’s possession or held in stock.

COMPLICATIONS

Patients wearing a TCL are at risk of the same complications as any patient wearing an extendedwear lens (see Ch. 7), but are even more vulnerable to infection. This is particularly true of those with neurotrophic keratitis and dry eye syndromes and those with diabetes. It has been reported that the organisms involved are mainly Gram-positive organisms, and this differs from organisms found in cosmetic lens wearers, in which the organisms are mainly Gram negative. It was thought that this

difference may be the result of the use of prophylactic antibiotics in the therapeutic lens wearer.14 A considerable number of TCL wearers are on topical corticosteroid medication and should be monitored carefully for evidence of infection and raised intraocular pressure.

Deposits form more readily on dry eyes, on silicone rubber lenses and on extended-wear lenses and may cause redness, irritation and giant papillary conjunctivitis.

Minimizing risks

Risks can be minimized by assessing corneal sensation, and by treating any pre-existing condition, such as blepharitis, before applying a lens. The patient must be given written instructions describing urgent symptoms, and explaining what to do in this eventuality.

It is important to have in place a system that ensures the patient attends for regular follow up, and that 24-hour care is available and can be reached by the patient.

Changing the lens regularly will minimize deposits.

MEDICATION

Topical medication is essential for most of these patients, either for treatment of the corneal condition or for a concurrent condition such as glaucoma, and these may not be available in an unpreserved form. Preserved drops can be used, particularly at four times a day or less, but the clinician needs to be aware of possible toxic and allergic reactions and, where possible unpreserved drops should be used.

Therapeutic lenses are a useful adjunct to other ophthalmological treatments, but require careful fitting and intensive supervision and both patient and clinician must be prepared to accept this responsibility.

3.O’Brart DPS, Kerr Muir MG, Marshall J. Phototherapeutic keratectomy for recurrent corneal erosions. Eye 1994;8:378–383.

4.Millis E. Management of ocular surface disease. Contact Lens and Anterior Eye 1996;19:37–40.

5.Kaluyci D, Basci N, Kortunay S, et al. Penetration of topical ciprofloxacin by presoaked medicated soft contact lenses. CLAO J 1999;22:182–184.

6.Srur M, Dattas D. The use of disposable contact lenses as therapeutic lenses. CLAO J 1997;23:40–42.

7.Rubinstein MP. Disposable contact lenses as therapeutic devices. J Br Contact Lens Assoc 1995;18:95–97.

8.Gupta S, Arora R, Sota LD, Kumar M. An alternative approach to bandage contact lenses. CLAO J 1998;24:118–121.

9.Lim L, Tan DTH, Chan WK. Therapeutic use of Bausch and Lomb PureVision contact lenses. CLAO J 2001;27:179–185.

10.Gomes JAP, Rapuano CJ, Cohen EJ. Topographic stability and safety of contact lens use

after penetrating keratoplasty. CLAO J 1996;22:64–69.

11.Aquavella JV, Musco PS, Veda S, Locascio JA. Therapeutic applications of a collagen bandage lens: a preliminary report. CLAO J 1988;14:47–50.

12.Bouchard CS, Lemp MA. Tight lens syndrome associated with 24-hour disposable collagen lens: a case report. CLAO J 1991;24:141–142.

13.Taravella M, Stepp P, Young D. Collagen shield delivery of tobramycin to the human eye. CLAO J 1998;24:166–168.

14.Kent HD, Cohen EJ, Laibson PR, Arentson JJ. Microbial keratitis with corneal ulceration associated with therapeutic soft contact lenses. CLAO J 1990;16:49–52.

Aquavella JV. Therapeutic contact lenses. In: Contact Lenses: A Guide To Basic Science and Clinical Practice, ed. Kastl PR, vol III, pp 67–75. Iowa: Kendall/

Hunt; 1995.

Christie CL. Therapeutic contact lenses. Contact Lens and Anterior Eye 1999;22(Suppl.1):S20–S25.

Mackie IA. Therapeutic uses of contact lenses. In: Contac Lens Practice: A Systematic Approach, pp 164–190. Oxford: Butterworth Heinemann;1993.

Wilson MS, Millis E. Therapeutic soft contact lenses. In: Contact lenses in Ophthalmology, pp 120–125. Oxford Butterworth Heinemann;1988.

CHAPTER CONTENTS

Pharmacokinetics 137 Anti-infective drugs 140 Anti-inflammatory drugs 143 Ocular decongestants 145 Mydriatics 145

Topical anesthetics 146 Vital dyes 147

Lubricants and wetting drops 147 References 148

Further reading 148

PHARMACOKINETICS

A drug is a substance that, when taken into a livin organism, may modify one or more of its func tions. It may be a synthetic or natural substanc and is usually intended for the diagnosis, cure treatment or prevention of disease.

Pharmacokinetics considers the absorption distribution, metabolism and excretion of drugs.

Absorption

Drugs used in the diagnosis and treatment of th anterior eye are frequently given as drops instille into the lower fornix. The drug mixes with th tears to form a solution of unknown concentration Passive diffusion is the most important means o absorption into the cornea and conjunctiva. Th drug must be lipid soluble to cross the corneal cel membrane and enter the epithelium. Drugs in solu tion are present in ionized and nonionized forms, th exact ratio being determined by the pH of the solu tion. It is the nonionized form that is lipid soluble.

The concentration of the drug in the tears alter rapidly as a fresh supply of tears dilutes the solu tion. Drops should be instilled singly and shoul not be larger than 20 l. More, or larger, drop cause increased tearing and dilute the dose Increased tearing takes 5 minutes to return to nor mal, and so more drops, whether of the same o a different drug, should only be applied after 5-minute interval. Drop volume has been shown to vary significantly between manufacturers. Th handling angle was also a factor – an angle les

than 60° gave a smaller drop. Larger drops were associated with drugs in high concentration, and those in multidose bottles. The type of drug, possibly related to its viscosity, and the nozzle parameters were also influential.

Factors affecting absorption

Factors affecting absorption are as follows:

●Drugs may enter the eye from the lower fornix by crossing the conjunctiva and passing through the sclera.

●The cornea acts as a barrier due to the presence of tight junctions in the epithelium. If these are damaged greater amounts of drug can penetrate into the cornea.

Increasing contact with the eye increases absorption. This may be achieved with very viscous substances, such as methylcellulose, polyvinyl alcohol, hyaluronic acid, or using an ointment or gel as a vehicle for the drug.

●Lipid solubility is more important than water solubility if drugs are to pass through the corneal epithelium into the hydrophilic stroma.

●Preservatives, which are present in most drops, damage human cell membranes as well as those of microorganisms and result in increased permeability.

●The higher the concentration the greater the permeability of the drug.

●Large molecules cannot penetrate the epithelial barrier, whereas substances with a low molecular weight enter more readily.

Distribution

The blood– ocular barrier makes it difficult for many substances, administered systemically, to reach their target in sufficient concentrations. To avoid this, other routes, such as subconjunctival injection, intravitreal injection or corneal application may be used in some cases. Drugs reach the anterior chamber in 30–60 minutes and may then diffuse towards the limbus where they enter the systemic circulation. They leave the anterior chamber in the flow of aqueous. Some drugs bind to melanin and this can be seen in the longer time it

takes for mydriatics to take effect in dark brown eyes, and the prolonged mydriasis that occurs in light-colored eyes. Timolol and some antibiotics bind to melanin.

Drops are sufficient for most ocular surface infections and high concentrations may be obtained in the cornea by this means. Subconjunctival injections are only needed if compliance is poor.

Metabolism

Metabolism of drugs may take place in the eye by means of enzymes present in the ocular tissues. For those drugs that enter the systemic circulation, metabolism occurs mainly in the liver.

Excretion

In addition to those drugs that leave the anterior chamber a considerable amount is lost via the nasolacrimal system and may then be absorbed systemically by the very vascular nasopharyngeal mucosa. Drugs may be excreted by skin and gut, but most are excreted by the kidney. Drugs may also be excreted by breast milk, and for this reason some drugs should not be given to lactating mothers.

Nomenclature

Every drug has three types of name:

●a chemical name

●an approved name, which is shorter

●a commercial name (sometimes several).

The approved and commercial names are used most commonly. Prescriptions should be written using approved names. Examples are chloramphenicol, for which the commercial name may be Chloromycetin® or Sno-phenicol®, and fluoromethalone, which is commercially named FML®.

Vehicles for drug delivery

Drops

Normally multidose bottles of drops must contain a preservative and can then be used over a period of 4 weeks. Unpreserved multidose drops, which can only be used for one week, are available from some hospital pharmacies.

The most common preservative in eye drops is benzalkonium chloride, which acts by interfering with the permeability of the bacterial cell membrane. Chlorhexidine acts in a similar manner. Thimerosal is a mercurial preservative and is used much less commonly now because it can cause an allergic keratoconjunctivitis.

Preservatives have been implicated as a cause of sensitivity reactions, ocular irritation and dry eye. Toxicity reactions are more likely to occur if drops are used more than four times a day, or if there is any ocular surface disease.

The effect of the drug may be increased, and systemic absorption minimized by applying pressure to occlude the lacrimal system during and after application of the drops. Keeping the eyelids closed for 1–2 minutes after instillation also enhances the effect of the drug.

Ointments

Ointments usually contain petrolatum and mineral oil with lanolin. Some patients are allergic to lanolin. Most of the water-soluble drugs are present in ointments as microcrystals, which are dispersed throughout the ointment. Only those crystals at the ocular surface can have an effect, and the duration of action of the drug is increased as more crystals are brought to the surface and released by the shearing action of the eyelids and melting of the ointment. Although release occurs over a longer period, the concentration of drug achieved may not be so great as with frequently applied drops. Despite the prolonged effect, the drug application does not last all night unless the instillation is repeated.

Ointment has several disadvantages. It blurs the vision, it can act as a barrier to other substances, and it remains on the eye, coating lashes and contact lenses. It is present on the eye on waking, even when it was applied before going to sleep.

Gels

Gels are less sticky than ointments. They include methylcellulose, polyvinyl alcohol and poloxamer 407. They increase the contact time between the

drug and the eye, and the active drug is release from the gel in the same way as from an ointment Preservatives in gels include benzalkonium chloride, cetrimide, disodium edetate, and ben zododecinium bromide. They may cause toxicit and allergic reactions and are not suitable for us

with contact lens wear.

Prodrug

Some drugs such as dipivefrine are activated b enzymes in the eye, to produce the effective form of the drug, in this case epinephrine. Prodrugs ar usually more lipophilic than their active counter parts and are therefore a means for these agents t cross the cornea and reach the site of action.

Soft contact lenses

Soft contact lenses may be pre-soaked in a solutio containing the drug. They result in a prolonged but variable release of the drug into the eye a drug from the surface of the lens is released ini tially, and that from deeper in the lens is release later. Drug release is also influenced by the state o hydration of the lens.

Christensen2 has shown that if, before drops ar instilled, lenses are removed from the eye fo 5 minutes the amount of drug taken up by the len is minimized and binding of BKC is reduced.

Collagen shields

Collagen shields are biodegradable lenses mad from porcine collagen that can be soaked in th drug and placed on the eye. They dissolve after specified period of days. They have been used t deliver antibiotics and anti-glaucoma drugs, but ar not used commonly. This method would improv compliance and maintain delivery of a drug ove time. Sleep would be undisturbed, and this tech nique is less painful and less likely to cause perfora tion than a subconjunctival injection.3

The amount of drug is dependent on the initia concentration of the solution, the water conten and thickness of the lens. Thicker, higher wate content lenses deliver greater amounts of th drug.

Mechanism of action

Mechanisms of action of drugs are as follows:

●Drugs may combine with enzymes to activate or inhibit their actions.

●A drug may alter cell membrane permeability by attaching to receptors on the membrane.

●The drug may replace a part of the metabolic chain resulting in the formation of an inactive compound, which blocks the metabolic pathway.

●A drug may act with the cell membrane to produce cyclic adenosine monophosphate (cAMP), which produces the effect of the drug intracellularly.

If a drug stimulates receptors to function normally it is an agonist, and if it gives rise to the opposite effect it is an antagonist.

Lack of response to treatment may be due to poor compliance, an inadequate dose, drug resistance or drug interactions.

Management of drops in the practice

All unopened drops are sterile. Once open, sterility is compromised, but preservatives in multidose containers are adequate to give protection for up to 4 weeks of domestic use. Unpreserved drops may be used for 1 week provided they are kept in the fridge. In clinic, and sometimes domestically, it is more practical to use unit dose, preservativefree drops such as Minims® (Chauvin), which can be discarded after a single use. These are available for antibiotics, anti-glaucoma drops, mydriatics and miotics; also corticosteroid drops and diagnostic dyes, saline and topical anesthetics.

Compliance

Good compliance increases the effectivity of treatment, but is often not achieved. It is particularly important that patients should understand the reason for the treatment, for how long it should continue, and why.

With few exceptions only those who are medically qualified can, at the present time, prescribe drugs, but it is important that all contact lens practitioners should understand the uses and actions of medication being taken by their patients.

This review will consider those drugs most likely to be encountered by the contact lens clinician.

ANTI-INFECTIVE DRUGS

Antibiotics are substances that kill microorganisms, or inhibit their growth. Microbiological specimens taken for microscopy and culture can help identify which antibiotic would be most appropriate for a particular infection.

Gram’s stain is a method of staining that aids the microscopic identification of the bacteria, Grampositive organisms retain the color of the gentianviolet stain, while Gram-negative organisms lose the color and take the color of the counter stain. Organisms grown on culture plates can be used to test their sensitivity to different antibiotics.

Chloramphenicol

Chloramphenicol is the most commonly used topical antibiotic in the UK. It has a broad spectrum of activity against Gram-positive and Gram-negative organisms, and also chlamydia, but is not effective against pseudomonas. It acts by binding to the bacterial ribosomes and prevents protein synthesis. It is bacteriostatic – that is it inhibits or retards bacterial growth, but does not kill the organism. It is very lipid soluble, and so enters the cornea easily. It is rarely used systemically because of the risk of aplastic anemia, but Walker et al.4 have shown that the serum concentration of topically applied chloramphenicol was below detectable levels and conclude that, used topically, the drug is not a risk factor for inducing dose-related bone marrow toxicity.

Chloramphenicol is instilled as drops into the lower fornix four times a day for conjunctivitis, and hourly for microbial keratitis, if it is indicated, reducing to four times a day as the infection is controlled. The patient should continue to use the drops until 48 hours after resolution.

Chloramphenicol is also available as ointment, which is applied at night. If it is necessary to use it during waking hours it is applied three or four times a day. Ointment should be avoided in contact lens wearers, even at night, because the residue persists into the next day and coats the lenses.

Chloramphenicol may cause transient stinging, and an unpleasant taste as it enters the pharynx via the nasolacrimal system.

Aminoglycoside antibiotics

Aminoglycoside antibiotics include gentamicin, neomycin, and tobramycin. They inhibit protein synthesis and are bactericidal – that is they will kill microorganisms, by causing lysis of the cell membrane. They are effective against Grampositive and Gram-negative organisms. Gentamicin and tobramycin are active against Pseudomonas aeruginosa, but neomycin is not. They are useful in infection with Staphylococcus aureus and Staphylococcus epidermidis.

pseudomonas infection. It causes epithelial toxicity but has been used with collagen shields. Frequen topical use may lead to significant serum level and it is used only rarely.

Cephalosporins

Cephalosporins are similar to penicillin and should not be used in patients with a history of sensitivity to penicillin. The group includes cefazolin cefuroxime and ceftazidine. They are bactericidal acting against a broad spectrum of organisms by inhibiting synthesis of the bacterial cell wall. Cef tazidine is effective against Pseudomonas aerugi nosa, so can be very effective in microbial keratitis.

Gentamicin

Although the penetration of the eye is poor when the cornea is intact and there is no inflammation, therapeutic levels of gentamicin are achieved if the cornea is damaged or the eye inflamed. It is effective in a wide range of infections, including pseudomonas infections, if it is used in a fortified form. This is not available commercially, but is made by the hospital pharmacy.

In microbial keratitis drops must be instilled every hour day and night until the condition has improved. Gentamicin is now rarely used as such doses are toxic to the epithelium and cause marked hyperemia and punctate keratitis. The corneal and conjunctival epithelium may also show concentric lamellae of gentamicin, which accumulate in the lysosomes.

Neomycin

Neomycin is a bactericidal antibiotic that has a broad spectrum of activity against Gram-positive and Gram-negative organisms. It is often combined with other drugs.

Neomycin is available as drops or ointment, but is best avoided because it is a frequent cause of allergies. It is useful for treating Acanthamoeba infection.

Tobramycin

Tobramycin is active against Acanthamoeba and is more effective than gentamicin in the treatment of

Fluoroquinolones

This bactericidal group of drugs damage bacteria DNA and break the double strands. They ar effective against Gram-positive and -negative bac teria, including Pseudomonas aeruginosa, although some strains are developing resistance. Applied topically they produce a longlasting concentration in the tears. They should not be used for babies o less than 1 year of age, during pregnancy, or in lac tating mothers.

Fluoroquinolones are commonly used as first line treatment in the management of microbia keratitis and endophthalmitis, and therefor should not be used for more minor conditions o prophylaxis.

Ciprofloxacin

Ciprofloxacin may be used as a single agent in th treatment of microbial keratitis. This reduces th risk of contamination and increases the chance o compliance, but may cover an inadequate spec trum of organisms and cause a hypersensitivity reaction, or be toxic to the epithelium.

Ciprofloxacin may cause burning and itching tearing and photophobia. Superficial punctat keratitis may occur and white corneal precipitate of crystalline drug have been reported, and simi lar deposits may form on soft contact lenses.5 Thi is the result of evaporation of the fluid phase o the drug from the lens surface that was not com pletely covered by solution. It can be removed by