Many ophthalmic preparations are used in the practice of medicine. You
probably know solutions, suspensions, and ointments are commonly used as
ophthalmic products. Most ophthalmic products are no longer prepared in the
pharmacy. However, you should be familiar with some of the characteristics of these important products.
DEFINITION OF OPHTHALMIC PREPARATIONS
Ophthalmic preparations are sterile products that are intended to be applied to the eyelids or placed in the space between the eyelids and the eyeball.
TYPES OF OPHTHALMIC PREPARATIONS
Three types of ophthalmic preparations are commonly encountered in the
pharmacy. Each type of preparation has its advantages and disadvantages.
a. Solutions. Ophthalmic solutions are rather easily placed into the eye.
However, care must be taken to ensure the solution remains in the eye in order to produce the desired therapeutic effect. Ophthalmic solutions usually do not impair or interfere with the vision of the patient.
b. Suspensions. Ophthalmic suspensions are also easily placed into the eye.
In general, suspensions produce a longer effect than do solutions. Suspensions do
have one disadvantage; it is difficult to ensure that the suspension does not contain
particles large enough to produce eye irritation.
c. Ointments. Ophthalmic ointments (for example, certain antibiotic ointments)
are commonly used. They are relatively easy to apply (except in the eyes of children).
Ophthalmic ointments remain in contact with the eye tissues for an extended period.
Hence, they usually produce a therapeutic effect of long duration. One major disadvantage of ointments is that they leave a film over the patient's eye.
Thus, the patient's vision can be impaired.
General principles involved in the extemporaneous compounding of ophthalmic preparations
There are several important factors to consider when called upon to compound a sterile ophthalmic preparation . In many cases, the drugs involved have a narrow therapeutic range and even small errors when introduced have the potential to cause irreversible damage to the eye. Unfortunately, it is not difficult to locate court cases that have centered around loss of sight of a patient due to a compounding error. The following considerations are recommended whenever you prepare such a product.
1- Ensure that there is adequate support in the literature for the product that is prescribed and that the requested concentration is within an acceptable range. Also make sure that there is not a suitable commercial product available that would eliminate the need to extemporaneously prepare a product. The advent of new formulations in the past few years has already drastically reduced the need for many previously compounded items.
2- Sterility of the final product is a must: strict adherence to aseptic technique as well as any other preventative measures must be in place.
3- The pH of the final product must be within an acceptable range.
4- Anticipated stability of the final product must be known, as well as the recommended storage requirements
5- Adequate knowledge of potential diluents or vehicles is required in order to ensure proper tonicity, viscosity, or dissolution of the final product
6- Establishment of written procedures that fully ******** each step is an important consideration in order to reduce the likelihood of errors. Whenever calculations are required, there should be a secondary source available to verify the accuracy. Also, if multiple dilutions are needed, it is recommended that a new syringe be used for each step in order to minimize the impact of residual contents. One should also use the smallest possible syringe for each measurement in order to increase accuracy.
7- If the preparation of a product requires the breaking of an ampule or the reconstitution of a powder (e.g. cefazolin), it is recommended that the final product be filtered prior to packaging in order to eliminate any particulate matter.
8- The preparation of intra-ocular products requires the use of preservative-free ingredients. Many preservatives have been found to be toxic to the inner ocular tissues.
9- Finally, before dispensing the finished product, always indicate the storage requirements, concentrations of ingredients, and the expected expiration date.
Drugs are administered to the eyes in a wide variety of dosage forms,some of which require special consideration.They are discussed in the following paragraphs.
Ophthalmic ointments are ointments for application to the eye.Special precautions must be taken in the preparation of ophthalmic ointments.They are manufactured from sterilized ingredients under rigidly aseptic conditions and meet the requirements.If the specific ingredients used in the formulation do not lend themselves to routine sterilization techniques,ingredients that meet the sterility requirements ,along with aseptic manufacture,may be employed.Ophthalmic ointments must contain a suitable substance or mixture of substances to prevent growth of,or to destroy,microorganisms accidentally introduced when the container is opened during use,unless otherwise directed in the individual monograph,or unless the formula itself is bacteriostatic
The medicinal agent is added to the ointment base either as a solution or as a micronized powder.The finished ointment must be free from large particles and must meet the requirements for Leakageand for ****l Particles.The immediate containers for ophthalmic ointments shall be sterile at the time of filling and closing.It is mandatory that the immediate containers for ophthalmic ointments be sealed and tamper-proof so that sterility is assured at time of first use.
The ointment base that is selected must be nonirritating to the eye,permit diffusion of the drug throughout the secretions bathing the eye,and retain the activity of the medicament for a reasonable period under proper storage conditions.
Petrolatum is mainly used as a base for ophthalmic drugs.Some absorption bases,water-removable bases,and water-soluble bases may be desirable for water-soluble drugs.Such bases allow for better dispersion of water-soluble medicaments,but they must be nonirritating to the eye.
Ophthalmic solutions are sterile solutions,essentially free from foreign particles,suitably compounded and packaged for instillation into the eye.Preparation of an ophthalmic solution requires careful consideration of such factors as the inherent toxicity of the drug itself,isotonicity value,the need for buffering agents,the need for a preservative (and,if needed,its selection),sterilization,and proper packaging.Similar considerations are also made for nasal and otic products.
Lacrimal fluid is isotonic with blood,having an isotonicity value corresponding to that of a 0.9%sodium chloride solution.Ideally,an ophthalmic solution should have this isotonicity value;but the eye can tolerate isotonicity values as low as that of a 0.6%sodium chloride solution and as high as that of a 2.0%sodium chloride solution without marked discomfort.
Some ophthalmic solutions are necessarily hypertonic in order to enhance absorption and provide a concentration of the active ingredient(s)strong enough to exert a prompt and effective action.Where the amount of such solutions used is small,dilution with lacrimal fluid takes place rapidly so that discomfort from the hypertonicity is only temporary.However,any adjustment toward isotonicity by dilution with tears is negligible where large volumes of hypertonic solutions are used as collyria to wash the eyes;it is,therefore,important that solutions used for this purpose be approximately isotonic.
Many drugs,notably alkaloidal salts,are most effective at pHlevels that favor the undissociated free bases.At such pHlevels,however,the drug may be unstable so that compromise levels must be found and held by means of buffers.One purpose of buffering some ophthalmic solutions is to prevent an increase in pHcaused by the slow release of hydroxyl ions by glass.Such a rise in pHcan affect both the solubility and the stability of the drug.The decision whether or not buffering agents should be added in preparing an ophthalmic solution must be based on several considerations.Normal tears have a pHof about 7.4and possess some buffer capacity.The application of a solution to the eye stimulates the flow of tears and the rapid neutralization of any excess hydrogen or hydroxyl ions within the buffer capacity of the tears.Many ophthalmic drugs,such as alkaloidal salts,are weakly acidic and have only weak buffer capacity.Where only 1or 2drops of a solution containing them are added to the eye,the buffering action of the tears is usually adequate to raise the pHand prevent marked discomfort.In some cases pHmay vary between 3.5and 8.5.Some drugs,notably pilocarpine hydrochloride and epinephrine bitartrate,are more acid and overtax the buffer capacity of the lacrimal fluid.Ideally,an ophthalmic solution should have the same pH,as well as the same isotonicity value,as lacrimal fluid.This is not usually possible since,at pH7.4,many drugs are not appreciably soluble in water.Most alkaloidal salts precipitate as the free alkaloid at this pH.Additionally,many drugs are chemically unstable at pHlevels approaching 7.4.This instability is more marked at the high temperatures employed in heat sterilization.For this reason,the buffer system should be selected that is nearest to the physiological pHof 7.4and does not cause precipitation of the drug or its rapid deterioration.
An ophthalmic preparation with a buffer system approaching the physiological pHcan be obtained by mixing a sterile solution of the drug with a sterile buffer solution using aseptic technique.Even so,the possibility of a shorter shelf-life at the higher pHmust be taken into consideration,and attention must be directed toward the attainment and maintenance of sterility throughout the manipulations.
Many drugs,when buffered to a therapeutically acceptable pH,would not be stable in solution for long periods of time.These products are lyophilized and are intended for reconstitution immediately before use (e.g.,Acetylcholine Chloride for Ophthalmic Solution).
The sterility of solutions applied to an injured eye is of the greatest importance.Sterile preparations in special containers for individual use on one patient should be available in every hospital,office,or other installation where accidentally or surgically traumatized eyes are treated.The method of attaining sterility is determined primarily by the character of the particular product Whenever possible,sterile membrane filtration under aseptic conditions is the preferred method.If it can be shown that product stability is not adversely affected,sterilization by autoclaving in the final container is also a preferred method.
Buffering certain drugs near the physiological pHrange makes them quite unstable at high temperature.
Avoiding the use of heat by employing a bacteria-retaining filter is a valuable technique,provided caution is exercised in the selection,assembly,and use of the equipment.Single-filtration,presterilized disposable units are available and should be utilized wherever possible.
Ophthalmic solutions may be packaged in multiple-dose containers when intended for the individual use of one patient and where the ocular surfaces are intact.It is mandatory that the immediate containers for ophthalmic solutions be sealed and tamper-proof so that sterility is assured at time of first use.Each solution must contain a suitable substance or mixture of substances to prevent the growth of,or to destroy,microorganisms accidentally introduced when the container is opened during use.
Where intended for use in surgical procedures,ophthalmic solutions,although they must be sterile,should not contain antibacterial agents,since they may be irritating to the ocular tissues.
Apharmaceutical grade of methylcellulose (e.g.,1%if the viscosity is 25centipoises,or 0.25%if 4000centipoises)or other suitable thickening agents such as hydroxypropyl methylcellulose or polyvinyl alcohol occasionally are added to ophthalmic solutions to increase the viscosity and prolong contact of the drug with the tissue.The thickened ophthalmic solution must be free from visible particles.
Ophthalmic suspensions are sterile liquid preparations containing solid particles dispersed in a liquid vehicle intended for application to the eye (see Suspensions).It is imperative that such suspensions contain the drug in a micronized form to prevent irritation and/or scratching of the cornea.Ophthalmic suspensions should never be dispensed if there is evidence of caking or aggregation.
Fluorescein sodium solution should be dispensed in a sterile,single-use container or in the form of a sterile,impregnated paper strip.The strip releases a sufficient amount of the drug for diagnostic purposes when touched to the eye being examined for a foreign body or a corneal abrasion.Contact of the paper with the eye may be avoided by leaching the drug from the strip onto the eye with the aid of sterile water or sterile sodium chloride solution.
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Diseases & Drugs
infective conjunctivitis
Infective conjunctivitis can be bacterial, viral, chlamydial or fungal in origin. Staphylococcus species are the most common infecting bacteria in the United Kingdom, but others include streptococcus and haemophilus species.3 Viral infection may be caused by adenovirus and Herpes simplex virus. Chlamydia infection causes trachoma, which is the greatest cause of preventable blindness worldwide. Fungal conjunctivitis is rare in the UK, but may be encountered in rural areas.
Infective conjunctivitis is characterized by a diffuse redness of the conjunctiva with a purulent (bacterial) or watery (viral) discharge. Viral infections are commonly associated with upper respiratory tract infections and swollen pre-auricular nodes.
Most cases of infective conjunctivitis are self-limiting but can be treated with the antimicrobial diamidines propamidine isethionate or dibromopropamidine isethionate.
Antimicrobials Historically, Golden Eye ointment contained mercuric oxide. This product was discontinued because of concerns about absorption and the adverse effects of inorganic mercury. In 1992, the brand name was used again when Golden Eye drops and ointment were reintroduced. These new products contain a diamidine as an antimicrobial and are an alternative to the well-established brand Brolene.
Brolene and Golden Eye drops contain the diamidine propamidine isethionate which has antibacterial, trypanocidal and fungicidal activity and is active against Staphylococcus aureus, Streptococcus pyogenes and certain other streptococci and clostridia.
The ointment preparations contain dibromopropamidine isethionate which has antibacterial and antifungal properties. It is active against pyogenic cocci, Staphylococcus aureus, and certain Gram-negative bacteria, including Escherichia coli, Proteus vulgaris and some strains of Pseudomonas aeruginosa. Fungi susceptible to the drug include Aspergillus niger and Candida albicans. The antibacterial activity of these diamidines is not reduced in the presence of organic matter, such as tissue fluids, pus and serum.
Both drops and ointment are licensed as "an anti-infective for use in local infections of the superficial structures of the eye due to micro-organisms sensitive to its action." The products may be used in adults and children at a frequency of up to four times a day for the drops and once or twice a day for the ointment.
If no improvement is seen within two days, medical opinion should be sought.
The aim of antimicrobial therapy is to achieve a concentration of the antimicrobial agent at the site of infection high enough to kill or stop the growth of the infecting organism. It is doubtful that the licensed frequency of administration will achieve this, and Edwards and Stillman suggest hourly use of propamidine isethionate eye-drops.5
Combining this intensive therapy during the day with the longer-acting eye ointment at night will increase the possibility of resolving the infection.
Propamidine isethionate, in combination with a wide range of agents, has been used in the treatment of Acanthamoeba keratitis.6 This use of the product is outside its current product licence. Several types of hypersensitivity reactions in the eye are recognised. Those amenable to treatment with OTC medicines are of the immediate hypersensitivity type and include acute allergic conjunctivitis, seasonal or hay fever conjunctivitis and vernal keratoconjunctivitis.
In all cases, the disease process is thought to be initiated by allergens combining with immunoglobulin E which is bound to conjunctival mast cells. This interaction causes mast cell degranulation leading to the release of numerous chemical mediators, such as histamine.7 These mediators trigger the inflammatory cascade, resulting in vasodilatation, increased vascular permeability and oedema and give rise to the classical symptoms of allergic conjunctivitis (see Panel).
Preparations used to treat allergic conjunctivitis contain mast cell stabilisers, antihistamines, sympathomimetics and astringents.
Clinical features of allergic conjunctivitis
Signs
Hyperaemia (redness)
Eyelid swelling
Puffy eyelids
Ciliary flush
Peripheral corneal vascularisation
Diffuse infiltration of eosinophils
Symptoms
Itching and burning
Lachrymation
Foreign body sensation
Stinging
Watery discharge
Photophobia
Two mast cell stabilisers may be sold in the pharmacy for the prevention, relief and treatment of seasonal and perennial allergic conjunctivitis - sodium cromoglicate 2 per cent in the form of aqueous eye-drops in packs of up to 10ml, and nedocromil sodium in a container of not more than 3ml with a maximum strength of 2 per cent. Sodium cromoglicate may also be sold in the form of a 4 per cent eye ointment in packs of up to 5g for the treatment of acute seasonal allergic conjunctivitis.1 However, at the time of writing this article, there are no commercially-available preparations of sodium cromoglicate eye ointment; the prescription only product, Opticrom, was discontinued in 1998. As yet, no company has received a pharmacy licence for nedocromil.
Sodium cromoglicate eye-drops may be used in adults and children at a frequency of four times a day. As the drug has no intrinsic vasoconstrictor or antihistaminic activity, it should be used regularly to prevent symptoms. The drops have been shown to be superior to placebo in suppressing eye symptoms in seasonal allergic conjunctivitis. In a double-blind, placebo-controlled trial of sodium cromoglicate in 43 patients,8 both patients and physicians assessed sodium cromoglicate to be more effective than placebo. Another trial9 showed that there was a trend for associated nasal symptoms and the requirement for nasal beclomethasone to be lower in the treatment group.
In a randomised trial involving 62 adults with ragweed pollen conjunctivitis, subjects received sodium cromoglicate regularly four times a day or when needed, up to four times daily. The researchers concluded that there might be some additional therapeutic benefit from using sodium cromoglicate regularly throughout the ragweed pollen season.10 Although diary symptoms were similar in the two treatment groups, quality of life was better in the regular treatment group and the "when needed" group required more terfenadine for uncontrolled eye symptoms.
Topical sodium cromoglicate has been compared with oral antihistamines and found to be as effective as terfenadine and more effective and faster in relieving symptoms than astemizole.
In vernal keratoconjunctivitis, sodium cromoglicate eye-drops were found to be as effective as Decadron (dexamethasone sodium phosphate) and superior to Antistin-Privine (antazoline sulphate and naphazoline nitrate).
If nedocromil sodium becomes available as an OTC product, it has a number of advantages over sodium cromoglicate. Twice daily nedocromil sodium has been shown to be as effective as sodium cromoglicate four times daily.14 Nedocromil sodium is useful in patients with perennial allergic conjunctivitis unresponsive to sodium cromoglicate, and it produces a more rapid and marked improvement in symptoms of vernal keratoconjunctivitis than sodium cromoglicate.
Antihistamines Histamine released from mast cells causes dilatation of the small precapillary blood vessels and constriction of the larger venules, resulting in passive capillary dilatation. In addition, histamine causes oedema by constricting cells of the small venules, thus exposing the basement membrane and allowing plasma to pass into the extracellular space. In the eye, histamine release produces characteristic symptoms of ocular allergy: itching, redness, tearing and chemosis (build-up of fluid under the conjunctiva).
Oral H1-antagonists, such as astemizole and loratadine, are effective and generally well tolerated in seasonal allergic conjunctivitis. However, although these drugs are well absorbed after oral administration, it may take several hours to achieve maximum antihistaminic effects. With topical treatment, maximum therapeutic effects are achieved rapidly because the drug is applied directly to the affected organ. In addition, the risk of systemic adverse effects will be considerably reduced. There are two topical antihistamines available OTC: antazoline contained in Otrivine-Antistin, in combination with the sympathomimetic xylo****zoline, and the newer, more potent drug, levocabastine.
Antazoline Antazoline was introduced over 50 years ago and a paper published in 194818 reported that an ophthalmic solution of the drug proved of definite therapeutic value in 50 cases of ocular allergy.
The use of combination drops in allergic conjunctivitis is widespread and well accepted. Studies of such preparations have shown that they are useful in controlling symptoms and well tolerated by patients. Otrivine-Antisitin eye-drops are licensed for use in adults and children over five years at a frequency of two to three times daily.
Levocabastine In 1998, this new H1-antagonist, available on prescription as Livostin, became classified as a pharmacy medicine in the form of aqueous eye-drops for the symptomatic treatment of seasonal allergic conjunctivitis in a container of not more than 4ml. The OTC version of the drops, Livostin Direct, was launched in March,1999.
Levocabastine has been specifically developed for ocular and nasal administration. Its potency is significantly greater than that of antazoline.20 It does not display anticholinergic or antiserotonin activity21,22 and repeated instillations do not cause any sedative effects.23 Levocabastine has a rapid onset of action, providing relief from symptoms of histamine-induced conjunctivitis within 10 minutes of instillation24 and has a sufficiently long duration of action to permit a convenient twice daily dosage.
In a comparison between levocabastine and naphazoline/antazoline eye-drops in seasonal allergic rhinoconjunctivitis, significantly more patients using levocabastine rated it excellent. Patients using levocabastine also experienced fewer side effects.
A number of trials have compared levocabastine twice daily with sodium cromoglicate four times a day in the treatment of seasonal allergic conjunctivitis. Levocabastine was shown to be equally effective26-28 or more effective29 than cromoglicate. Moreover, levocabastine has been shown to be significantly more effective than sodium cromoglicate in inhibiting itching, redness, eyelid swelling, chemosis and tearing in an allergen challenge model of allergic conjunctivitis, and it inhibits the signs and symptoms of allergic conjunctivitis after a single instillation.30 However, in one study of children between six and 16 years of age,31 in which levocabastine or sodium cromoglicate were administered in addition to regular oral terfenadine, the sodium cromoglicate group experienced slightly fewer eye symptoms throughout the trial.
Several studies comparing topical levocabastine with oral antihistamines have shown that the topical drug is as effective as,32-34 or more effective than,35,36 the systemic antihistamine in relieving ocular symptoms. All these studies report that levocabastine was well tolerated. A significantly faster relief of ocular symptoms was seen with levocabastine eye-drops than with oral cetirizine in a study reported by Drouin et al.37 In a review of levocabastine, Bahmer concludes that the topical drug is an attractive alternative to oral antihistamines as a first-line therapy for the treatment of seasonal allergic rhinoconjunctivitis.
Levocabastine has also been shown to be effective and well tolerated in the treatment of vernal conjunctivitis,38,39 seasonal allergic rhinoconjunctivitis,40,41 and allergic conjunctivitis from house dust mite in a variety of patient groups, including children under 12 years of age.42 However, these indications are currently outside the licensed indications. The OTC preparation is only licensed for the symptomatic treatment of seasonal allergic conjunctivitis in adults and children over 12 years. In addition, although several studies have shown efficacy and lack of tachyphylaxis over periods of up to 16 weeks,43 the use of Livostin Direct eye-drops is currently limited to a total of four weeks in any one year.
Sympathomimetics Three sympathomimetic drugs are available in OTC remedies "for the temporary relief of redness of the eye due to minor eye irritation" or "as a decongestant for relief of minor eye irritation." Following topical application to the eye, constriction of conjunctival blood vessels occurs at concentrations that generally do not cause pupillary dilatation. These agents provide only palliative therapy, since they have no effect on the conjunctival response to antigen.16
Phenylephrine At the concentration used for ocular decongestion, 0.12 per cent, phenylephrine causes vasoconstriction by direct stimulation of a-receptors on conjunctival vasculature, causing a decrease in conjunctival hyperaemia and oedema. Dilatation of the pupil can occasionally occur, particularly if the corneal epithelium is damaged or diseased.44 Chronic use can cause a rebound of conjunctival congestion resulting in conjunctivitis medicamentosa.
Although phenylephrine is also classified as a pharmacy medicine in the higher strengths of 2.5 per cent and 10 per cent, and available as Minims phenylephrine hydrochloride in these strengths, these preparations are licensed not as decongestants but as mydriatics. Over-the-counter sale of both of these higher strength products should only be made if the patient is using the drug under the direction of an ophthalmologist.
Naphazoline Naphazoline is included in OTC eye-drops at a concentration of between 0.01 to 0.012 per cent, either alone or in combination with an astringent. The majority of clinical trials comparing naphazoline with other decongestants have used concentrations of the drug higher than those available in the UK.16 However, one study compared naphazoline 0.012 per cent with phenylephrine 0.12 per cent and tetrahydrozoline 0.05 per cent in 40 healthy adults.46 None of the drugs caused significant changes in pupil size or anterior chamber depth, however; naphazoline produced a somewhat higher average intraocular pressure than the control.
The use of naphazoline in products marketed as cosmetic products for "bright sparkling eyes" and "clearer whites" should be limited to occasional use, as the vasoconstriction produced by naphazoline will mask diagnostic signs of eye disease.
Xylo****zoline The effect of xylo****zoline is similar to naphazoline but its action is somewhat less intense and less prolonged and the drug is better tolerated by some patients.
Hurwitz states that it is of greatest value in surface ocular conditions with congestion of the conjunctiva lining the eyeball and eyelids and its attendant symptoms, ie, tearing, photophobia, blepharospasm and smarting. The vasoconstrictor action of xylo****zoline starts immediately after ocular instillation and continues for two to four hours. It is well tolerated with a minimal burning sensation.48 The author describes 48 cases and comments that the drug is "strikingly effective in relieving epiphora [watering], photophobia, conjunctival congestion, smarting and foreign body sensation, with 70 per cent of the patients being symptomatically relieved." Untoward symptoms consisted of mild, burning sensation and an occasional blurring of vision. No damage or irritation to the conjunctiva or cornea was seen.
In the UK, xylo****zoline is only available at a concentration of 0.05 per cent in combination with the antihistamine antazoline (see above) as Otrivine-Antistin. Trew et al49 studied 16 healthy subjects and recorded the sympathomimetic responses to evaluate any possible risks associated with the use of Otrivine-Antistin, which is contrainidicated in narrow angle glaucoma. The drops produced mild sympathomimetic responses in the eye: small, though statistically significant, changes in pupil diameter, palpebral height and conjunctival vessel diameter compared with the placebo vehicle. Importantly, the mydriatic response was too small to be of clinical significance or to impose any risk of pupil block or irido-corneal angle closure and thus of acute glaucoma, even in susceptible subjects. The eye-drops had no effect on corneal sensitivity or on intraocular pressure and produced some mild and transient irritation in some subjects, consistent with clinical experience. The authors concluded that Otrivine-Antistin produces mild sympathomimetic responses in the eye but that, in its use as a decongestant, these are harmless and impose no risk to the subject.
Adrenaline Adrenaline eye-drops, neutral BPC are also listed as a pharmacy medicine. However, as both commercially available preparations of this formulation, Eppy and Simplene, used for the treatment of primary open angle glaucoma, are classified as prescription only medicines, a request for a sale would be unlikely.
Astringents Preparations containing the astringents distilled witch hazel and zinc sulphate are indicated for the relief of minor eye irritations. Astringents are locally acting drugs that precipitate proteins. These preparations are so poorly penetrative that only the cell surface is affected, resulting in greatly reduced cell permeability and thus watering.19
Distilled witch hazel is employed at a concentration of 12.5 to 13 per cent v/v in products indicated for the temporary relief of redness of the eye due to minor eye irritations. Zinc sulphate, which also has a mild antiseptic properties, is employed at 0.25 per cent. There is little information in the literature on the efficacy of such preparations. In a study on eye irritation in hay fever, Clark et al reported that 71 per cent of patients derived benefit from Optrex eye lotion used three times daily.50 Another study, published in a French journal, reported a very good or excellent result in 78 per cent of cases after the addition of zinc sulphate to a topical antihistamine preparation.51 However, most authors are dismissive of the benefits of astringents. They have been described as of "doubtful value" and best recommended where no specific syndrome exists, for example, in cases where a patient complains of "tired eyes" but has no significant conjunctivitis.5,52
Severe cases of infective conjunctivitis should be referred for treatment with antibiotic therapy and cases of allergic conjunctivitis that are non-responsive to OTC medicines can be prescribed alternative mast cell stabilisers or antihistamines by the general practitioner. The term "dry eye" refers to a group of ocular disorders related to deficiencies in the quantity and/or quality of the tear film. Dry eye may result from dysfunction or absence of the meibomian glands which secrete the lipid component of the tears, deficiency of the basal mucin layer of the tears or aqueous tear film deficiency. A decreased blink rate or defective spreading of the tear film may also result in a dry eye.
Dry eye is most frequently encountered in menopausal and postmenopausal women, but can affect individuals at any age and of either sex. Non-pharmacological measures, such as the use of room humidifiers, may offer the patient a degree of relief but the mainstay of pharmacological treatment is artificial tears, many of which are available OTC.
Artificial tears Preparations containing substituted cellulose ethers of high viscosity, such as methylcellulose, used in ophthalmology since 1945,54 are useful in aqueous tear deficiency. Other substituted cellulose ethers, particularly hydroxyethylcellulose and hydroxypropylmethylcellulose (hypromellose), are somewhat less viscous than methylcellulose but possess cohesive (film-forming) and emollient properties equal or superior to those of methylcellulose. However, although viscous agents enhance the ocular retention time of tear substitutes, high viscosity itself does not provide relief for all dry eye conditions.
Other less viscous hydrophilic substances, such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (povidone or PVP), have been included as the polymeric ingredients of many artificial tear formulations.
The tears of patients with dry eyes due to aqueous deficiency have been shown to have a higher osmolarity than normal subjects,56 a factor which may be responsible for the ocular surface disease in this condition.57 In such patients, hypotonic solutions such as polyvinyl alcohol 1 per cent with an osmolarity of 150 mOsm/L have been shown to be superior to an isotonic solution of 300 mOsm/L in providing symptom relief.58,59
Ingredients such as PVA and PVP impart good wetting properties to the corneal surface and are therefore useful in patients with mucin deficiency. PVA at a concentration of 1.4 per cent has surface tension equivalent to normal tears and optimal wetting characteristics. All these preparations have been shown to prolong tear break up time, a measure of the stability of the tear film.60,61
Patients with mild dry eye may benefit from instillation of one of these artificial tear drops up to four times a day. However, in moderate to severe cases, these preparations need to be instilled more frequently.
To overcome this problem, preparations containing a longer-acting polymer, polyacrylic acid, also known as carbomer 940, have been introduced. Such preparations have a much longer retention time in the eye and symptom relief is obtained with significantly fewer instillations.62,63
Fewer instillations of an artificial tear preparation will also expose the patient to less preservative load, an important factor because benzalkonium chloride, the preservative most frequently used in artificial tear preparations has been shown to be toxic to the corneal endothelium.64 Göbbels and Spitznas65 have shown a decrease in epithelial permeability in patients treated with unpreserved polyvinylpyrrolidone 2 per cent, while those receiving the same preparation preserved with benzalkonium chloride 0.005 per cent showed an increase in permeability. The authors suggest that, in dry eyes, treatment with unpreserved artificial tears may lead to an objective improvement in corneal surface disease, with this effect being counteracted by preservation of tear substitutes with benzalkonium chloride.
An extensive range of preservative-free artificial tear preparations is now available. Although Göbbels and Spitznas's findings would recommend their use in all patients, it is unlikely that patients purchasing dry eye products OTC would wish to bear the cost of unit dose preparations unless they fall into the category of patients in whom preserved eye-drops are contraindicated. These include patients allergic to, or intolerant of, preservative and patients who wear soft contact lenses.
Preparations vary in composition and viscosity and as patients with dry eye are very sensitive to such differences, the patient may need to try a range of preparations before settling upon one which suits them.
Lubricating ointments Ophthalmic lubricating ointments contain white soft paraffin, lanolin and liquid paraffin. These preparations melt at the temperature of the ocular tissue and are retained longer than other ophthalmic vehicles.66 They are not generally recommended as tear substitutes during the day as vision is blurred after instillation. They are, however, a useful adjunct to artificial tears if used at bedtime.
Lack of response to OTC preparations in patients with dry eye conditions warrants referral because ophthalmic examination may reveal underlying pathology amenable to medical or surgical correction.
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