Management of Contact Lens–Induced Pathology

Antimicrobial agents *

* Antimicrobials are substances that act against microorganisms (bacteria, viruses, fungi and/or protozoa). They can be either synthetically derived or produced by other organisms. Antibiotics are strictly substances produced by microorganisms to combat the growth of other microorganisms (bacteria, viruses, fungi and/or protozoa) and are not synthetically derived. Antibacterials are the largest class of antimicrobials and refer to agents that act selectively against bacteria. Selective toxicity means an agent that has the ability to kill the microbial cells but not the host cells.

Antimicrobial agents are used to manage infections by microorganisms. The key to their success is selective toxicity, * where there is little or reduced toxicity to the host organism when they are used at therapeutic concentrations. There are numerous commercially and non–commercially available agents used to manage common infections in contact lens wearers. The general principle of effective use of antibiotic agents is to use the minimum dosage per day (often four times a day) over the minimum treatment period (often 7–10 days) to produce effective outcomes while preventing the development of resistance. There have been discussions within the ophthalmic and wider medical literature regarding the use of antibiotics unnecessarily and the impact on resistance development ( , ).

A summary of the topical antimicrobial agents typically used in the management of contact lens–related complications is found in Table 17.1 .

Antibacterials ^* ( p. 345

* See footnote on antibacterials, [CR] .

)

Antibacterial agents generally target bacteria apparati that:

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  synthesise proteins

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  replicate DNA

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  maintain or synthesise the bacterial cell wall.

Due to the association of Gram-negative bacteria such as Pseudomonas aeruginosa with contact lens–related infections and complications, agents with ample Gram-negative activity (fluoroquinolones and aminoglycosides) are most frequently used when complications arise ( ).

The commercial availability and usage of the fluoroquinolones vary throughout the world. For example, in Australia, ophthalmic fluoroquinolone use is reserved for management of sight-threatening corneal infections, with routine use for conjunctivitis or prophylaxis actively discouraged in an effort to aid resistance prevention. In other areas, usage is much more liberal, with the newest, fourth-generation fluoroquinolones frequently used for both prophylaxis and active infection. Non–commercially available, compounded formulations are also occasionally used in the empirical management of corneal infections, with a combination of a Gram-positive covering cephalosporin (5% cephalexin) paired with a Gram-negative covering aminoglycoside (1.4% gentamicin or tobramycin) to ensure the broadest spectrum of activity possible ( ).

Antifungals

The most common commercially available antifungal agent is a 5% natamycin suspension (Natacyn, Alcon). Natamycin is generally well-tolerated and provides broad antifungal activity against filamentous fungi but may not be as effective with deeper stromal infections ( ). Other agents such as Amphotericin B and the azoles (ketoconazole, fluconazole, voriconazole) are occasionally used but must be compounded ^†

† Compounding is the mixing or combining of drugs to produce a compound that is tailored for the patient. This includes when a different formulation (e.g. liquid for patients unable to swallow) or concentration of a drug is necessary. A drug that is compounded at a higher concentration than what is commercially available is referred to as ‘fortified’.

for topical use ( ).

Antiamoebic drugs

The US Food and Drug Administration does not currently approve any agents specifically for the treatment and management of Acanthamoeba ocular infections. Antiseptic agents such as polyhexamethylene biguanide (PHMB), chlorhexidine and propamidine are all used in combination to combat the trophic and cystic forms of the organism, although due to their nonselective activity, significant toxicity to the ocular surface is expected while undergoing treatment ( ).

Anti-inflammatory agents

The vast majority of contact lens–related complications which require therapeutic intervention are inflammatory in nature. Corticosteroids are the most potent anti-inflammatory agents used to manage these conditions, often with concurrent prophylactic antibacterial coverage. Corticosteroids are useful for short-term, acute inflammatory management. Long-term use is associated with increased risk of secondary infection, intraocular pressure (IOP) rises and cataract formation. The anti-inflammatory activity of different corticosteroids varies, from relatively weak activity with hydrocortisone to significant potency with dexamethasone, prednisolone and difluprednate. The dose of corticosteroids also has to be decreased gradually after prolonged usage to prevent rebound inflammation, a process known as “tapering” ( ).

Three other classes of anti-inflammatory agents are also commonly used ophthalmically:

• 1.

  Nonsteroidal anti-inflammatory drugs (NSAIDs) affect only one arm of the inflammatory cascade and thus are less efficacious at managing inflammation than corticosteroids but have less long-term side effects. They are also useful as a means of pain relief ( ).

• 2.

  Immunomodulators are used to manage inflammation and the immune response long term. Cyclosporine A is the most commonly used ophthalmic agent for the management of keratoconjunctivitis sicca (Hom et al. 2006).

• 3.

  Histamine anti-allergy agents affect a subset of the inflammatory cascade associated with allergy, and in most cases are safe for use long term. These agents work either to block the activity of histamine in producing signs and symptoms of allergy or to prevent the release of histamine from sensitised mast cells ( ).

A summary of the anti-inflammatory agents useful in the management of contact lens–related inflammatory conditions is summarised in Table 17.2 .

Cycloplegics

Topical cycloplegic agents used in eye care are in the antimuscarinic class, and work to inhibit actions of the parasympathetic nervous system. They are useful as adjunct management to paralyse the ciliary muscle and dilate the pupil to improve patient comfort and aid in management of anterior uveitis. Agents available include 0.5%–1% cyclopentolate, 2% and 5% homatropine and 1% atropine, with dosage between one and four times a day used, depending on the inflammation severity ( ).

Microbial Keratitis (Bacterial, Acanthamoeba, Fungal)

Infection of the cornea (microbial keratitis [MK]) is the most serious complication of contact lens wear as it threatens vision. In lens wearers, the majority of corneal infections are due to bacteria (bacterial keratitis) ( ). The type of causative bacteria varies with climate and the environment. For example, Pseudomonas aeruginosa (Gram-negative) keratitis is more prevalent in warmer climates, and keratitis associated with Staphylococcus aureus, a Gram-positive organism, predominates in cooler climates ( ). A small number of cases occur due to the protozoan Acanthamoeba and filamentary fungi and tend to be more severe than bacterial keratitis.

The gold standard for diagnosis of corneal infection is corneal culture ( ). Samples are collected from the corneal lesion, and culture of organisms is attempted. Corneal cultures are only 50% sensitive, but the technique is essential in large, deep ulcers or where unusual or virulent organisms are suspected. Corneal polymerase chain reaction (PCR) investigations, in which samples of microbial DNA are amplified to facilitate rapid identification of causative organisms, is becoming more widely available and has higher sensitivity than corneal culture, but it cannot differentiate live versus dead organisms without manipulation ( ). Advances in ocular imaging, such as in vivo confocal microscopy, has also allowed visualisation of Acanthamoeba cysts and fungal elements and is available in some specialised centres, but the quality and sensitivity of these techniques in identifying organisms appears to be operator dependent ( ).

Bacterial Keratitis

The common symptoms of bacterial keratitis are:

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  pain

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  photophobia

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  redness

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  decreased vision

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  discharge.

The signs include:

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  A focal infiltrate and overlying epithelial defect (ulcer), anywhere on the cornea. Focal infiltrates appear:

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    large (>1 mm)

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    with irregular margins

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    composed of replicating microbes, inflammatory cells and necrotic tissue

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    showing diffuse inflammation and/or oedema of the surrounding corneal tissue.

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  Compromised vision even if the lesion does not cross the visual axis.

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  Conjunctival and limbal vessels are engorged across the entire ocular surface due to the robust immune and inflammatory response.

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  Bystander effects, such as lid swelling, conjunctival chemosis, and anterior chamber reaction (secondary anterior uveitis) are common.

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  Hypopyon – pus accumulation inferiorly in the anterior chamber. Tends to occur in severe cases. Fig. 17.1 illustrates a severe bacterial keratitis with hypopyon.

  

Keratitis due to Pseudomonas aeruginosa ( Fig. 17.2 ) is associated with contact lens wear and is of particular note as it can progress rapidly.

The hallmark signs of pseudomonas keratitis are corneal oedema and a ring abscess (defined as a circular infiltrate with a less-dense centre) ( ) although a ring abscess (ring infiltrates or Wessely rings *

* A Wessely ring is a Type 3 hypersensitivity response marked by antibodies interacting with antigens diffusing outward from an inflammatory source ( ).

; ) can also occur in other severe forms of keratitis.