Ординатура / Офтальмология / Английские материалы / Ophthalmic Drugs Diagnostic and Therapeutic Uses 5th edition_Hopkins, Pearson_2007
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258 OPHTHALMIC DRUGS
appear to be sight-threatening. Even problems that are normally selflimiting and without long-term sequelae, such as conjunctival haemorrhage, will cause concern to patients or their carers and result in requests for treatment. Treatment in these cases will reassure the patient and encourage compliance with other, non-medical components of the treatment.
CONTRAINDICATIONS AND PRECAUTIONS
Against the indications must be set certain general contraindications:
•Toxicity: very few drugs have no side-effects and the adverse responses produced by ophthalmic preparations must be borne in mind when selecting the treatment (Table 16.1). Adverse effects can vary from stinging or irritation on instillation to more cumulative effects on long-term treatment, such as the rise in intraocular pressure produced by topically applied steroids.
•Hypersensitivity: in addition to the adverse effects produced by the pharmacology or toxicology of the drug, additional problems can arise from hypersensitivity reactions caused by allergic and other mechanisms. These can be just as serious, if not more so, than adverse
Table 16.1
Drug category |
Precaution |
Anti-bacterials |
Must be used with caution in pregnancy, lactating mothers and infants under the |
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age of 1 year. |
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Anti-virals |
These agents are relatively toxic and may lead to a punctate keratopathy. |
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Anti-fungals |
These are toxic to the corneal epithelium and lead to superficial punctate |
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keratopathy. If used together, polyenes and imadazoles may antagonize each |
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other and reduce effectiveness. |
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Corticosteroids |
Contraindicated in acute superficial herpes simplex keratitis and fungal keratitis. |
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Corticosteroids may potentiate herpes simples virus replication and their long- |
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term use may increase intraocular pressure and induce cataract. |
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Non-steroidal |
Occasionally implicated in the development of sterile corneal infiltrates and |
anti-imflammatory |
sterile keratolysis. |
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Vasoconstrictors |
Excessive systemic absorption may cause hypertension and long-term use can |
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cause an acute or chronic inflammatory conjunctivitis due to the preservative. |
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Mydriatics and |
Will cause photophobia. Adults should not drive or operate machinery while the |
cycloplegics |
pupils are significantly dilated. Mydriatics have the potential to induce angle- |
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closure glaucoma in patients with shallow anterior chamber angles. |
INDICATIONS AND CONTRAINDICATIONS FOR OPHTHALMIC DRUGS 259
drug responses. It is important during history taking to ascertain whether the patient has a history of allergy.
•Drug interactions: although drug interactions generally involve systemically administered drugs and/or foods, there is a possibility that a topically administered drug could interact with a systemically administered one.
•Cost: this is rightly place at the end of the contraindications and should play little part in the selection of treatment. In terms of cost per day’s treatment, ophthalmic drugs are relatively cheap.
In examining the various conditions that are amenable to medical treatment, it is useful to divide acute from chronic conditions:
•Acute conditions: although they might be recurrent, acute conditions have a definite time course at the end of which the problem should be eradicated. Treatment for these conditions is aimed at resolving the problem as quickly as possible without causing further problems.
•In the treatment of chronic conditions, slightly different criteria have to be applied to selecting dose regimens. Unfortunately, it is often necessary to modify the treatment as the condition develops and treatment is usually very long term, unless other methods of treatment are employed such as surgery.
Bruce & Loughnan (2003) identified certain specific precautions in the use of ophthalmic drugs. Precautions relevant to drugs used in the treatment of glaucoma are mentioned in Chapter 14.
Many topical ophthalmic preparations utilize benzalkonium chloride as a preservative that has the capacity to bind to hydrogel contact lenses. Most conditions requiring treatment will oblige the patient to suspend contact lens wear. However, where contact lens wear is essential, they can be inserted 15 min after each instillation of preserved drops.
ACUTE CONDITIONS
These generally fall into three groups:
•infections and infestations
•allergies
•inflammations.
GENERAL PRINCIPLES OF TREATING INFECTIONS
AND INFESTATIONS
In principle, treatment is aimed at the swift eradication of the offending organism, with as few adverse effects on the host as possible. To achieve this it is important to select the correct drug at the right dose for the right length of time.
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Drug Given sufficient time and funds, it would be ideal to carry out a swab to identify the offending microorganism. However, the delay might lead to serious long-term effects, apart from the inconvenience to the patient. In addition, the organisms present in the conjunctival sac might not be the ones that are causing the problem. It is possible, that an eye exhibiting signs and symptoms of bacterial anterior segment will present a sterile conjunctival sac. It is, therefore, advisable to take the pragmatic view and use an antibiotic with a broad antibacterial spectrum with activity against the range of bacteria normally associated with bacterial conjunctivitis.
Dose Depending on the strain of bacteria present, it is important to maintain a minimum inhibitory concentration. These vary greatly, but can normally be achieved with the concentrations of antibacterials found in modern ophthalmic formulations providing that the drops are applied with sufficient frequency. The half-life of an aqueous drop is so short that 60 min after the drop has been applied little of the drug remains. Hourly dosing is not excessive!
Duration It is important that treatment should be continued for some time after the signs and symptoms have apparently disappeared. The level of infection might have been reduced below the clinical level but might able to increase again when the chemotherapeutic agent is discontinued. There is a real possibility of the emergence of resistant strains of the infecting organism(s).
GENERAL PRINCIPLES OF TREATING ALLERGIES
In general, treatment of allergies has a two-pronged approach. First, there is the removal of the allergen, wherever possible. If this is present in the environment (e.g. pollen in the case of hay fever), then this might not be possible. However, the allergen might be a medicinal product (either the actual pharmacological agent or some excipient) or some other item used personally by the patient (e.g. cosmetics or toiletries) or, in the case of a generalized reaction, some item of food. In these latter situations, it is important to identify and then isolate the offending chemical. Second, palliative, symptomatic treatment can be used in the form of antihistamines or mast cell stabilizers, which are aimed at alleviating the signs and symptoms of the condition.
GENERAL PRINCIPLES OF TREATING INFLAMMATION
Inflammation can arise from a variety of causes and, when possible, the primary cause (e.g. infection) should be treated. Whether or not this can be achieved, it is important to relieve signs and symptoms and to prevent
INDICATIONS AND CONTRAINDICATIONS FOR OPHTHALMIC DRUGS 261
any permanent damage occurring as a result of the inflammatory processes. These can include corneal scarring, adhesions between the iris and nearby structures such as the lens and cornea and secondary glaucoma.
A number of diseases affecting the anterior segment of the eye have been selected to provide graphic examples of the topical application of the various categories of ophthalmic drugs. The outline of treatment represents a consensus derived from various sources and is intended merely to illustrate the use of drugs and is not to be regarded as either a comprehensive or definitive account.
SOME COMMON ACUTE CONDITIONS
Phthiriasis palpebrarum/ pediculosis
Treatment
Figure 16.1 Lice and nits clinging to the lashes in phthiriasis palpebrarum (reproduced from Kanski 2003, with permission).
EYELIDS
Key features
This is a unilateral, or more usually bilateral, infestation of the eyelid by the crab louse, Phthirus pubis, normally associated with transmission by sexual contact. It is an indicator of poor hygiene. The patient complains of mild to moderate constant itching and irritation of the eyelids. Inspection will reveal the presence of live lice as well as eggs (nits) and empty shells (casts) adhering to the lashes (Fig. 16.1).
Forceps are used to remove both lice and eggs and prevent re-infestation. The irritation will subside as a result of the eradication of the lice.
A bland ophthalmic ointment such as yellow soft paraffin can be applied three times a day for up to 10 days to smother the lice and nits. Several insecticides are based on the long-acting anticholinesterases, or parasiticidal preparations such as permethrin 1%, which are indicated for the removal of lice and scabies. Some solutions are alcohol-based and care must be taken in their application. Clothing and bedding need to be washed thoroughly.
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Figure 16.2 Vesicles due to primary herpes simplex infection (reproduced from Kanski 2003, with permission).
Herpes simplex |
Key features |
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blepharitis |
Although herpes infections are normally associated with the cornea, |
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unilateral or bilateral infections of the eyelids can occur, typically in |
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children. These appear as small, fluid-filled vesicles that crust over and |
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heal in a few days. There is mild to moderate discomfort of the affected |
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area, sometimes with lacrimation and photophobia (Fig. 16.2). |
Treatment |
Initially, treatment is aimed at reducing eruptions and preventing |
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corneal or conjunctival involvement. Complete eradication of the virus |
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can be difficult. Two antiviral creams are available (aciclovir and |
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ganciclovir), which can be applied to the lids at regular intervals, care |
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being taken to avoid contact with the eye. However, some clinicians |
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question the value of antiviral therapy even when there is an accom- |
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panying keratitis. |
Anterior blepharitis |
Key features |
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Anterior blepharitis is a chronic inflammation of the lid margin caused |
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by either a staphylococcal infection or a more generalized seborrhoeic |
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problem, often affecting the scalp and face. The patient complains of a |
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foreign body sensation (i.e. burning, grittiness and photophobia) and |
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there is a redness of the lid margin caused by the inflammation. Crusting |
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is noted and often there are scales on the surface of the lids (Fig. 16.3). |
Treatment |
Although resolution of symptoms is the primary aim, chronic infective |
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blepharitis can lead to lid scarring and madarosis. Treatment is tedious |
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and consists of lid hygiene using either commercially available lid wipes |
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or weak solutions of baby shampoo or sodium bicarbonate. |
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Infective blepharitis will require antibiotic treatment. Tear substitutes |
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are helpful if the tear film is unstable. If secondary papillary conjunc- |
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tivitis, toxic epitheliopathy or marginal keratitis is present, a weak |
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corticosteroid such as fluoromethalone is required. |
INDICATIONS AND CONTRAINDICATIONS FOR OPHTHALMIC DRUGS 263
Figure 16.3 Hard scales in staphylococcal blepharitis (reproduced from Kanski 2003, with permission).
External hordeolum |
Key features |
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(stye) |
A relatively common problem caused by a pyogenic staphylococcus |
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infection of the lash follicle. A stye normally begins with a redness and |
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tenderness at the lid margin. The patient might experience a foreign |
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body sensation. Eventually a yellow spot will occur at the centre of the |
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swollen area (Fig. 16.4). |
Treatment
Figure 16.4 External hordeolum (stye) (reproduced from Kanski 2003, with permission).
Treatment is aimed at the resolution of the infection and the relief of symptoms. Warm compresses held over the closed lids for 15–20 min, four times daily, can help to reduce the inflammation. Antibacterial treatment with chloramphenicol or fusidic acid ointments can shorten the course of the infection and should be prescribed very soon after the onset of the condition.
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Simple bacterial conjunctivitis
Treatment
Figure 16.5 Severe crusting of the eyelids in bacterial conjunctivitis (reproduced from Kanski 2003, with permission).
CONJUNCTIVA
Key features
A common, often self-limiting, condition caused by a variety of organisms, some of which are normally present in the conjunctival sac as commensals.
The eye presents with a conjunctival hyperaemia of sudden onset, accompanied with grittiness and a mucopurulent discharge. This is most noticeable in the morning because of the crusty deposits on the lids. Both eyes are normally affected, because of cross-contamination, but one eye is usually affected first (Fig. 16.5).
Although the condition is often self-limiting and will usually resolve in less than 2 weeks if left untreated, it is advisable to treat the condition to improve cosmetic appearance, relieve the symptoms and reduce the possibility of more serious sequelae such as corneal involvement.
Cleaning the lids and lashes will accelerate resolution of the condition as it will remove much of the bacterial load and allow the antibacterial agent easier access. A wide range of topical antibacterial agents is available. The most commonly used preparations are:
•Chloramphenicol: should be applied every 1–2 hours for 2 days and then reduced to four times a day. Some practitioners advocate the use of drops during the day and ointment at night.
•Fusidic acid: being a gel preparation, needs to be applied only twice a day.
•Other antibacterials: these are available but their use is rarely justified due to the efficacy of chloramphenicol or fusidic acid and the desirability of keeping other antibiotics in reserve to treat more serious infections.
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INDICATIONS AND CONTRAINDICATIONS FOR OPHTHALMIC DRUGS |
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Clinical note |
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It is important that the patient continues treatment for some time after |
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the signs and symptoms have disappeared to avoid the re-appearance of |
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the infection with a new-resistant organism. |
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Chlamydial |
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Key features |
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conjunctivitis |
Chlamydial trachomatis infection is normally sexually associated with |
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pelvic inflammatory disease in females and urethritis in males. Typically, |
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the affected patient is a teenager or young adult. Infection can be |
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unilateral or bilateral and presents with an irritable, slightly red eye with |
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a watery or mucopurulent discharge which can become chronic if not |
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treated. Following papillary hypertrophy, follicles develop in the tarsal |
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conjunctiva and forniceal conjunctiva and there is sometimes keratitis |
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with subepithelial marginal infiltrates (Fig. 16.6). The preauricular lymph |
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node is often tender and palpable. |
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Treatment |
Initially it is important to eradicate the causative organism and relieve |
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the symptoms. Long-term infections can lead to conjunctival scarring |
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and corneal pannus. Topical treatment consists of antibiotic ointment |
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utilizing tetracycline two to four times daily for at least 3 weeks. Oral |
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antibiotic treatment might be required. |
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Allergic rhinoconjunctivitis
Figure 16.6 Large conjunctival follicles in adult chlamydial infection (reproduced from Kanski 2003, with permission).
Key features
As its name suggests, this is an ocular response to a variety of allergens. It can be a seasonal allergic conjunctivitis, when the allergens are pollens and the condition is associated with the general symptoms of hay-fever (sneezing with a watery nasal discharge) and occurs during spring and early summer. Perennial allergic conjunctivitis is less marked but can
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Figure 16.7 Allergic rhinoconjunctivitis (reproduced from Kanski 2003, with permission).
occur all the year round, probably more pronounced in the autumn. In this condition, the allergens might be house-dust mites. The presenting symptoms of allergic conjunctivitis are of itching and grittiness in the eyes which appear inflamed and watery (Fig. 16.7).
Treatment As removal of the allergen is almost impossible, treatment is usually symptomatic and is aimed at relieving the signs and symptoms. Application of a cool compress several times a day offers some relief.
As the majority of symptoms of allergic conjunctivitis are mediated through histamine, most treatments are at reducing the effects of this substance. Physiological antagonists such as the vasoconstrictor conjunctival decongestants (xylometazoline, naphazoline) produce immediate but short-term relief for 1 or 2 hours and are not recommended for long-term use because rebound vasodilation will occur. Antihistamines (e.g. azelastine, emedastine, levocabastine) or prophylactic use of mast cell stabilizers (e.g. lodoxamide, nedocromil, sodium cromoglicate) provide longer relief and the latter protect from the effects of the allergy. Ketotifen and olopatadine are antihistamines that also have the ability to stabilize mast cells.
Vernal Key features
keratoconjunctivitis Vernal keratoconjunctivitis is a far more serious problem than allergic (spring catarrh) rhinoconjunctivitis. It is often associated with general atopic conditions such as eczema and asthma. It most often affects children and young adults, especially males. As one would expect from the name, the problems appear to be worst during spring and early summer. The main symptoms are bilateral intense itching and tearing associated with a feeling of grittiness. A shield ulcer can cause photophobia and blurring of vision. The superior tarsal conjunctiva can exhibit giant papillae up to
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Figure 16.8 ‘Cobblestone’ papillae in severe vernal disease (reproduced from Kanski 2003, with permission).
Treatment
a few millimetres in diameter and there is an accompanying thick mucous discharge. Untreated, it can lead to epithelial erosions and ulcers (Fig. 16.8).
Apart from the relief of symptoms, it is important that the more serious sequelae are avoided. The cornea, rather than the conjunctiva, is the principal target for treatment. Medical treatment is aimed at suppressing the inflammation. Topical steroids, such as fluoromethalone, used intermittently, might be required in short, high-dose treatments to prevent permanent damage. Severe cases might require supratarsal injection of a steroid. In addition, mast cell stabilizers such as cromoglicate of nedocromil (up to four times a day) can be employed with antihistamines. As mast cell stabilizers act prophylactically, their use should commence several weeks before the onset of spring. Acetylcysteine, which has a mucolytic action, also has a place in the treatment of this condition.
Giant papillary |
Key features |
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conjunctivitis/contact |
This condition used to be a common occurrence in optometric practice |
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lens induced papillary |
and was principally associated with hydrogel contact lens wear. A poorly |
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conjunctivitis |
fitting contact lens leading to irritation of the superior palpebral con- |
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junctiva, or an allergic reaction to a contact lens solution or an immu- |
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nological reaction to a lens deposit, were considered to be the most |
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common causes. Giant papillary conjunctivitis can sometimes be |
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induced by a protruding suture or by an ocular prosthesis having a |
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rough surface. The patient complains of slight itching, increased aware- |
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ness of the lens, excessive lens movement, mucous discharge, decreased |
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lens tolerance and intermittent blurring of vision. The condition owes |
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its name to the papillae on the superior tarsal conjunctiva, which, in |
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advanced cases, may exceed 1 mm in diameter (Fig. 16.9). |