General principles

There are several methods of achieving therapeutic drug concentrations within the eye and its surrounding structures. By far the most common is topical administration but, when higher concentrations of the drug are required, local injection or systemic administration is considered. Prescription and/or administration of the latter is most commonly initiated in the Eye Clinic, with the exception of a few conditions, e.g. suspected cases of giant cell arteritis.

Topical administration

Eye drops

• Principally absorbed through the cornea but absorption through conjunctival mucosa also occurs, giving rise to systemic effects.
• High intra-ocular concentrations are achieved if applied regularly.¹
• Drops may be in solution form (clear, e.g. anaesthetic drops) or in suspension (cloudy, e.g. steroids).
• There is a short drug-eye contact time so they tend to need a more frequent application.

Eye ointments

• Ointments allow a prolonged contact time; therefore, less frequent applications are required (good for night use).
• Help lubrication so that concurrent lubricant use is not always necessary (unless there was previous intensive usage or there is a large abrasion).

Eye lotions

These are solutions used for irrigation of the conjunctival sac (to flush out particles and chemical irritants). Sterile normal saline is the norm but clean water will do in an emergency.

Systemic absorption of topical drugs

• This occurs more readily with drops than with ointment; absorption occurs via conjunctival vessels.
• It can be limited to some degree by compressing the medial punctum and nasolacrimal sac on drop application ('press your finger firmly over your lids, next to the nose').⁸
• The fellow eye may be affected by systemic absorption of the drug applied to the treated eye.¹
• A common culprit is betablockers - check risk factors.
• Usual rules regarding pregnant and breast-feeding patients apply.

Multiple drug treatment

• If the patient needs more than one drop, allow 5 minutes between each drop.
• If there is a mixture of drops and ointments: instil drops first and then ointment after 4-5 minutes.
• Topical and systemic treatment: check for duplication (e.g. betablockers) and drug interactions (e.g. carbonic anhydrase inhibitors and loop diuretics).

Avoiding microbial contamination

• Use single application packs in the surgery clinic/emergency department (e.g. fluorescein drops).
• Wash hands before and after application; this is particularly important if you suspect, or are treating, infective eye disease.
• Discard bottles 28 days after opening.

'Drop allergy' - preservative toxicity²

A wide variety of preservatives is used in ophthalmic topical medication to keep it sterile. These preservatives may be toxic to the precorneal tear film and about 10% of patients also experience a hypersensitivity reaction to the preservatives, notably to the most commonly used one: benzalkonium chloride.¹ They may experience redness, itching, burning, blurring of vision and, in more severe cases, punctuate keratitis (tiny spots of fluorescein uptake on the cornea) or corneal oedema (the cornea goes hazy). The patient often clearly relates symptoms with starting the drops. Change to single-dose drops: Minims® (they come in little individual plastic vials that can only be used once). Check with the ophthalmology team if there is doubt over a link between drops and symptoms and signs.

High phosphate concentration in eye drops may be harmful to the cornea (this was noted with phosphate used as a buffer for sodium hyaluronate artificial tears).⁹

Topical drugs and contact lens wear¹⁰

• If treatment is initiated in the community, it is essential that you should be happy that you are not treating a CL-induced corneal ulcer: this needs specialist treatment and monitoring.
• Avoid soft CL wear with drops unless preservative-free; hard lens wear is acceptable.
• Remove soft CLs before instilling drops and wait for at least 15 minutes before re-inserting them. With rigid (hard) corneal CLs, drops may be instilled while wearing the lens.⁴
• Ointments and oily eye drops are not compatible with CL wear.⁴

Common difficulties in topical administration - and helpful tips

• Drop instillation can be tricky ("I can't touch my eyes, Doc", elderly patient with rheumatic hands): consider an ointment alternative or a drop dispenser (handed out by pharmaceutical companies for their individual product: talk to the dispensing chemist). Dispensers are re-usable.
• Ointment can be messy or awkward and can give rise to contact dermatitis:¹ wipe excess away after application or consider drops.
• Adherence to treatment for chronic eye conditions (e.g. glaucoma) may be improved by simplifying eye drop regimes, providing adequate information and giving individualised support.¹¹

Local injections and systemic treatment

Local injections: what to expect

If a patient is told that they will have an 'injection in the eye' (such as the local anaesthetic before cataract surgery or steroid treatment in severe uveitis), they will experience the following:

• An anaesthetic drop will be administered.
• A small spring will be applied to hold the lids open (painless).
• A small incision is made in the conjunctiva: they should not feel it.
• They will probably feel the agent being infiltrated in: the sub-Tenon approach is favoured (Tenon's fascia is a tough fibrous coat around the globe) - the needle does not penetrate the globe.
• The spring is removed and a pad is placed over the eye.
• Discomfort/pain varies between individuals and depends on what is being injected.
• Patients will commonly have a red eye or may have a small subconjunctival haemorrhage afterwards: this should begin to resolve over 24-48 hours.

Systemic treatment for ophthalmic problems

Physiological barriers limit systemically administered drug penetration to the eye, although this improves in inflamed states. Examples of systemic drugs used for eye conditions are antibiotics for orbital cellulitis, steroids for giant cell arteritis and acetazolamide for severely raised intra-ocular pressure. Another important area of systemic drug prescription for ophthalmic problems is to control pain, e.g. following a corneal abrasion. Topical local anaesthetics are not recommended (other than at the point of initial assessment); oral paracetamols and non-steroidal anti-inflammatory drugs (NSAIDs) are suitable choices in these patients.

Systemic treatment for systemic problems: effect on the eye

Ocular side-effects from systemic drugs, such as cataract formation from prolonged systemic steroid use, can occur. Other examples are listed below:^10,12

• Amiodarone: corneal deposits.
• Anticonvulsants: ocular motility dysfunction.
• Atropine: pupillary dilation.
• Digoxin: abnormalities of colour vision.
• Ethambutol, quinine: optic neuropathy.
• Hydroxychloroquine, chloroquine: retinal changes and corneal deposits.
• Isosorbide dinitrate: transient myopia.
• Opiates: pupillary constriction.
• Phenothiazines: retinal changes and ocular motility dysfunction.
• Sulphonamides and NSAIDs: Stevens-Johnson syndrome.
• Tamoxifen: retinal changes.

A number of drugs interfere with contact lens (CL) wear, including the oral contraceptive pill, aspirin, drugs affecting blink rate and drugs affecting lacrimation.⁴ See the separate articles Contact Lenses (Types and Care) and Contact Lens Problems for more information.

Over-the-counter eye preparations¹³

There are a number of commonly used over-the-counter preparations, examples of which include:

• Antihistamines, e.g. Otrivine-Antistin®.
• Antimicrobials, e.g. Brolene®, Golden Eye Ointment®, chloramphenicol antibiotic drops.
• Artificial tears, e.g. Viscotears®, Lacri-Lube®.
• Astringents, e.g. Eyedew Clear®, Optrex Fresh Eyes®.
• Mast cell stabilisers, e.g. Opticrom® allergy eye drops.

Research

There is interest and research into methods of delivering drugs to the posterior segment of the eye.¹⁴

Document references

1. Forrester JV, Dick AD, McMenamin PG, Lee WR. The Eye: Basic Sciences in Practice (2nd ed.) 2002, WB Saunders
2. Glaucoma, Clinical Knowledgs Summaries (September 2010)
3. How to use eye ointment, Pharmweb - National Pharmaceutical Association, Accessed December 2010
4. British National Formulary; 60th Edition (September 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)
5. How to give your child eye drops, Great Ormond Street Hospital for Children, September 2006
6. How to give your child eye drops, A short video from Great Ormond Street Hospital for Children (2008)
7. IGA; International Glaucoma Association's Information Service
8. Salminen L; Review: systemic absorption of topically applied ocular drugs in humans. J Ocul Pharmacol. 1990 Fall;6(3):243-9. [abstract]
9. Bernauer W, Thiel MA, Kurrer M, et al; Corneal calcification following intensified treatment with sodium hyaluronate Br J Ophthalmol. 2006 Mar;90(3):285-8. [abstract]
10. Batterbury M, Bowling B. Ophthalmology: An Illustrated Colour Text, 2002, Pp56-57 Churchill Livingstone ISBN: 0-443-05537-8
11. Gray TA, Orton LC, Henson D, et al; Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006132. [abstract]
12. Patel M. Optometry Today - Ocular Side-Effects of Systemic Drugs 1999-2003
13. Titcomb LC; Over-the-counter ophthalmic preparations. The Pharmaceutical Journal 264 (7082), p212-218 February 5, 2000.
14. Fischer N, Narayanan R, Loewenstein A, et al; Drug delivery to the posterior segment of the eye. Eur J Ophthalmol. 2010 Nov 11;21(S6):20-26. [abstract]

Acknowledgements