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Medicinal products promoted, recommended or marketed for use as eye-drops or eye ointments are not available for general sale — they are all classified as pharmacy medicines.1 Although ophthalmic complaints did not feature as one of the top 10 ailments for self-treatment recently described by Huw and Noyce,2 there are a number of eye disorders which may be treated by over-the-counter (OTC) preparations.
Conjunctivitis is the first condition discussed in this article. This disorder is an inflammation of the mucous membrane that lines the eyelids and covers the anterior surface of the eye (excluding the cornea). Conjunctivitis may result from microbial infection or be allergic in origin. Both types are amenable to treatment with OTC preparations.
The OTC treatment of dry eye conditions is also discussed in this article. Table 1 describes the preparations available for OTC treatment of conjunctivitis, dry eye conditions and other minor eye irritations.
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. Chlamydial 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.4
Infective conjunctivitis is characterised 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.
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.
Panel: Clinical features of allergic conjunctivitis
- Hyperaemia (redness)
- Eyelid swelling
- Puffy eyelids
- Ciliary flush
- Peripheral corneal vascularisation
- Diffuse infiltration of eosinophils
- Itching and burning
- Foreign body sensation
- Watery discharge
Mast cell stabilisers
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 terfenadine11 and more effective and faster in relieving symptoms than astemizole.12
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).13
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.15
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).16
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.17 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 xylometazoline, and the newer, more potent drug, levocabastine.
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.19 Otrivine-Antisitin eye-drops are licensed for use in adults and children over five years at a frequency of two to three times daily.
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.25
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.36
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.
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
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.45
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 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.
The effect of xylometazoline is similar to naphazoline but its action is somewhat less intense and less prolonged and the drug is better tolerated by some patients.47
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 xylometazoline 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, xylometazoline 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 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.
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.
Dry eye conditions
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.53
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.55
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.
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.
- Medicines, Ethics and Practice. A guide for pharmacists. Number 22. London: The Royal Pharmaceutical Society of Great Britain, 1999.
- Huw D, Thomas V, Noyce PR. The interface between self-medication and the NHS. BMJ 1996;312:688-91.
- Seal DV, Barrett SP, McGill JI. Aetiology and treatment of acute bacterial infection of the external eye. Br J Ophthalmol 1982;66:357-60.
- Armstrong RA, Smith SN, Titcomb LC. Fungi and the eye. Opt Today 1997;May:32-5.
- Edwards C, Stillman P. Minor illness or major disease? (5) Eye disorders. Pharm J 1993;250:839-43.
- National Acanthamoeba Keratitis Study Group. Acanthamoeba keratitis: multicentre survey on England 1992-6. Br J Ophthalmol 1998; 82:1387-92.`
- Rowley S. Conjunctivitis: causes, diagnosis and management. Prescriber 1997;8:33-44.
- Lindsay-Miller ACM. Efficacy of sodium cromoglycate eye drops in the treatment of seasonal allergic conjunctivitis. Clin Allergy 1979;9:271-5.
- Kray KT, Squire EN Jr, Tipton WR, Selner JC, O’Dea J, Nelson HS. Cromolyn sodium in seasonal allergic conjunctivitis. J Allergy Clin Immunol 1985;76:623-7.
- Juniper EF, Guyatt GH, Ferrie PJ, King DR. Sodium cromoglycate eye drops: regular versus “as needed” use in the treatment of seasonal allergic conjunctivitis. Ibid 1994;94:36-43.
- Leino M, Carlson C, Kilkku O, Kumpulainen T, Kyronpalo-Kauppinen S, Laaka V et al. The effect of sodium cromoglycate eye drops compared to the effect of terfenadine on acute symptoms of seasonal allergic conjunctivitis. Acta Ophthalmol 1992;70:341-5.
- Brough D, Olver M, Small K. Eficacia y velocidad del incio del cromoglycate del sodio en el tratamiento de sintomas oculares de la fiebre del heno. Review Espanol Allergologie and Immunologie 1987;2:293 (H980).
- El-Hennawi M. Clinical trial with 2 per cent sodium cromoglycate (Opticrom) in vernal keratoconjunctivitis. Br J Ophthalmol 1980;64:483-6.
- Leino M, Ennevaara K, Latvala AL, Nordgren P, Posti AM, Suves R et al. Double-blind group comparative study of 2 per cent nedocromil sodium eye drops with 2 per cent sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy 1992;22:887-8.
- Verin P. Treating severe eye allergy. Ibid. 1988;28(Suppl):44-8.
- Bartlett JD, Jaanus SD, editors. Clinical Ocular Pharmacology. 3rd ed. Boston: Butterworth-Heinemann,1995.
- Simons FER. H1-receptor antagonists. Clinical pharmacology and therapeutics. J Allergy Clin Immunol 1989;84:845-61.
- Hurwitz P. Antistine in ocular allergy. Am J Ophthalmol. 1948;31:1409-21.
- Ciprandi G, Buscaglia S, Canonica GW. Management of allergic conjunctivitis. Clinical Immunotherap 1996;5:374-91.
- Yanni JM, Stephens DJ, Parnell DW, Spellman JM. Preclinical efficacy of emedastine, a potent, selective histamine H1-antagonist for topical ocular use. J Ocular Pharmacol 1994;10:665- 75.
- Remsky A, Wolf S, Schulte S, Arend O, Reim M. Influence of levocabastine on accommodation in healthy subjects. Allergy 1993;48(Suppl):30.
- Bahmer FA. Topical levocabastine – an effective alternative to oral antihistamines in seasonal allergic rhinoconjunctivitis. Clin Exp Allergy 1995;25:220-7.
- Arriaga F, Rombaut N. Absence of central effects with levocabastine eye drops. Allergy 1990;45:552-4.
- Stokes TC, Feinberg G. Rapid onset of action of levocabastine eye drops in histamine-induced conjunctivitis. Clin Exp Allergy 1993;23:791-4.
- Bende M, Pipkorn U. Topical levocabastine, a selective H1-antagonist, in seasonal allergic conjunctivitis. Allergy 1987;42:512-5.
- Ciprandi G, Cerqueti PM, Sacca S, Cilli P, Canonica GW. Levocabastine versus cromolyn sodium in the treatment of pollen-induced conjunctivitis. Ann Allergy 1990;65:156-8.
- Wihl JA, Rudbald S, Kjellen H, Blychert LA. Levocabastine eye drops versus sodium cromoglycate in seasonal allergic conjunctivitis. Clin Exp Allergy 1991;21:37-8.
- Odelram H, Bjorksten B, Af Klercker T, Rimas M, Kjellman NIM, Blychert LO. Topical levocabastine versus sodium cromoglycate in allergic conjunctivitis. Allergy 1989;44:432-6.
- Frostad AB, Olsen AK. A comparison of topical levocabastine and sodium cromoglycate in the treatment of pollen-provoked allergic conjunctivitis. Clin Exp Allergy 1993;23:406-9.
- Stricker WE. The effects of levocabastine (a new, potent and specific histamine H1-receptor antagonist) vs cromolyn, in the allergen challenge model of allergic conjunctivitis. J Allergy Clin Immunol 1994;93:296.
- Njaa F, Baekken T, Bjaamer D, Holme JI, Korsrud F, Woxen O et al. Levocabastine compared with sodium cromoglycate eye drops in children with both birch and grass pollen allergy. Pediatr Allergy Immunol 1992;3:39-42.
- Bischoff P, Geber M. Levocabastine eye drops vs terfenadine in the treatment of allergic conjunctivitis. Allergy 1992;479(Suppl):305.
- Livostin Study Group. A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis. Ibid 1993;48:530-4.
- Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Ibid 1994;49:611-615.
- Sohoel P, Freng BA, Kramer J, Poppe S, Rebo R, Korsrud FR et al. Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis. J Allergy Clin Immunol 1993;92:73-81.
- Bahmer FA, Ruprecht KW. Safety and efficacy of topical levocabastine compared with oral terfenadine. Ann Allergy 1994;72:429-32.
- Drouin MA, Yang WH, Horak F. Faster onset of action with topical levocabastine than with oral cetirizine. Mediators Inflamm 1995;4:5-10.
- Blockhuys S, Goes F. Levocabastine eye drops in vernal conjunctivitis. Schweiz Med. Wochenschr 1991;121(Suppl):22.
- Goes F, Blockhuys S, Janssens M. Levocabastine eye drops in the treatment of vernal conjunctivitis. Doc Ophthalmol 1994;87:271-81.
- Vermeulen J, Mercer M. Comparison of the efficacy and tolerability of topical levocabastine and sodium cromoglycate in the treatment of seasonal allergic rhinoconjunctivitis in children. Pediatr Allergy Immunol 1994;5:209-13.
- Wuthrich B, Gerber M. Levocabastine eye drops are effective and well tolerated for the treatment of allergic conjunctivitis in children. Mediators Inflamm 1995;4:16-20.
- Tiszer Cesik E, Nowak W. A comparison of levocabastine and sodium cromoglycate in children with allergic conjunctivitis due to house dust mite. Allergy Clin Immunol News 1994;2:16.
- Parys W, Blockhuys S, Janssens M. New trends in the treatment of allergic conjunctivitis. Doc Ophthalmol 1992;82:353-60.
- Weiss DI, Shaffer RN. Mydriatic effects of one-eighth per cent phenylephrine. Arch Ophthalmol 1962;68:727-9.
- Ciprandi G, Buscaglia S, Cerqueti PM. Drug treatment of allergic conjunctivitis. Drugs 1992;43:154-76.
- Butler K, Thompson JP, Yolton DP. Effects of non-prescription ocular decongestants. Rev Optometry 1978;115:49-52.
- Hurwitz P. Otrivin in ophthalmology. Eye, Ear, Nose, Throat Monthly 1953;32:140-2.
- Hurwitz P. Ophthalmic Otrivin Solution. Am J Ophthalmol 1960;50:467-9.
- Trew DR, Wright LA, Smith SE. Otrivine-Antistin – pupil, corneal and conjunctival responses to topical administration. Eye 1989;3:294-7.
- Clark MJ, Chapman ND, Noyelle RM, Lancaster L. An open multiple dose study of Optrex Eye Lotion in eye irritation due to hayfever. Br J Clin Pract 1989;43:357-9.
- Favennec F, Catros A. Zinc et conjonctivites saisonnieres. Allerg Immunol (Paris) 1993;25:119-22.
- Li Wan Po A. Non-Prescription Drugs. London: Blackwell Scientific Publications, 1982.
- Woolard E, Frank M. Management of dry eye. On Continuing Practice 1991;18:41-5.
- Swan KC. Use of methylcellulose in ophthalmology. Arch Ophthalmol 1945;33:378-80.
- Blaug SM, Canada AT. Relationship of viscosity, contact time and prolongation of action of methylcellulose-containing ophthalmic solutions. Am J Hosp Pharm 1965;22:662-6.
- Gilbard JP, Farris RL, Santamaria II J. Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol 1978;96:677-81.
- Gilbard JP, Farris RL. Tear osmolarity and ocular surface disease in keratoconjunctivitis sicca. Ibid 1979;97:1642-6.
- Gilbard JP. Topical therapy for dry eyes. Trans Ophthalmol Soc UK 1985;104:484-8.
- Gilbard JP, Kenyon K. Tear diluents in the treatment of keratoconjunctivitis sicca. Ophthalmol 1985;92:646-50.
- Geeting DG, Baker SR. In vivo comparison of ocular lubricants in patients having reduced tear film break-up times. J Am Optometric Assoc 1980;8:757-80.
- Lemp MA, Goldberg M, Roddy MR. Effect of tear substitutes on tear film break up time. Invest Ophthalmol 1975;14:225-58.
- Brodwall J, Alme G, Gedde-Dahl S, Smith J, Lillliedahl NP, Kunz PA et al. A comparative study of polyacrylic acid (Viscotears) liquid gel versus polyvinylalcohol in the treatment of dry eyes. Acta Ophthalmol Scand 1997;75:457-61.
- Bron AJ, Mangat H, Quinlan M, Foley-Nolan A, Eustace P, Fsadni M et al. Polyacrylic acid gel in patients with dry eyes: a randomised comparison with polyvinyl alcohol. Eur J Ophthalmol 1998;8:81-9.
- Lemp MA, Zimmerman LE. Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride. Am J Ophthalmol 1988;105:670-3.
- Göbbels M, Spitznas M. Corneal epithelial permeability of dry eyes before and after treatment with artificial tears. Ophthalmol 1992;99:873-8.
- Hardburger R, Hanna C, Boyd CM. Effect of drug vehicles on ocular contact time. Arch Ophthalmol 1975;93:42-5.