Continuing Education

Professors Michael J. Doughty and Gordon N. Dutton describe the nature and use of an antibacterial agent available for use by optometrists (C4061, 2 standard CET points)

A new set of Statutory Instruments (SIs 2005 nos. 764, 765 and 766) introduced in 2005 allows all UK registered optometrists to use, sell and supply appropriate products containing a narrow spectrum antibiotic called fusidic acid. As with previous statutory instruments, this new revision does not define the eye disease that might be treated by the optometrist but only that the sale and supply of fusidic acid containing ophthalmic products should be “(a) in the course of their professional practice, and (b) in an emergency”. This article examines the common causes of a bacterial conjunctivitis, the mechanism of action of this narrow spectrum antibiotic as a bacteriostatic agent. The susceptibility of common ocular isolates of bacteria to fusidic acid as the basis for its indicated use for the treatment of bacterial conjunctivitis especially that caused by Staphylococcus sp. is also considered.

When to consider use of an antibiotic on a red eye

An infection of the external eye by common microbes results in a ‘red eye’ and a certain degree of discomfort. The so-called classic sign of a bacterial conjunctivitis has long been diagnosed on the basis of signs and symptoms at first presentation yet still can be the subject of specific clinical trials.5  In short, in addition to generalized redness (injection) of the bulbar and palpebral conjunctiva accompanied by a burning (rather than an itching) sensation, an isolated acute bacterial conjunctivitis can be asymmetrical in its initial development but can progress to affect both eyes if personal hygiene measures are inadequate (TABLE 1).

 Once both eyes are affected, the patient is likely to seek advice and so the initial presentation is often of a bilateral condition. The degree of redness will generally depend on the period of time that has elapsed since infection and presentation. Most bacteria that cause a conjunctivitis do not cause any haemorrhaging of the conjunctival vessels, but where there is concurrent upper respiratory tract infection (PCF) then petechial-type haemorrhages may be evident.

 A mucopurulent discharge leading to the eyelids being stuck together on wakening is still considered to be the hallmark sign of acute bacterial conjunctivitis. The eyelids may appear wet and matted with signs of a yellow-white discharge, or if not regularly cleansed, the discharge can dry to produce substantial encrustation of the eyelashes (FIGURE 1). Excess lacrimation in any form of ocular irritation (including infections caused by a virus, chlamydia, associated with PCF or even allergies) can result in slight deposits (and discomfort) along the lid margins as the tears evaporate (FIGURE 2). However, it is the extent of this and the gummy nature that is typical of a bacterial conjunctivitis.

 In chronic conditions associated with blepharitis, the redness is more likely to be bilateral, but usually less severe than if bacterial conjunctivitis is present. The matted nature of the eyelashes and accompanying redness (and tenderness) of the peri-ocular skin is typical of Staphyloccocal blepharo-conjunctivitis (FIGURE 3). Examination of the lower cul-de-sac will show the redness and the cloudy nature of the mucopurulent discharge (FIGURE 4). The amount of mucopurulent discharge in the lower cul-de-sac may well be very substantial in some instances.

 It is possible that there are differences in the amount of discharge if the bacteria causing the infection are uncommon strains.

 In some allergic presentations, whitish mucus strands or small clumps may be evident instead, either of which can also adhere to the eyelid margin. Eyelid oedema is not a sign of bacterial infection per se, but a reaction triggered by the innate immune system. Conjunctival or eyelid tissue oedema may be considered more likely to be associated with an allergic reaction.


 As part of the differential diagnosis, examination of the fornix or the palpebral conjunctiva (especially that over the tarsal plate) will show whether there is accompanying papillae or follicles, neither of which would usually be expected to be substantial if there was a simple bacterial cause of the conjunctivitis (Table 1). Testing the pre-auricular nodes for swelling and tenderness should be done, especially in children, to assess if the red eye infection is associated with a systemic viral infection. This sign may be pronounced in viral infections and PCF.

 In the vast majority of cases, especially at initial presentation, a presumptive diagnosis of bacterial conjunctivitis (or blepharo-conjunctivitis) will be made without the use of cultures. If however, the muco-purulent discharge is not yellow-white and / or heavily laden with mucous, then less common infectious causes should be considered. These should include STD’s (including Chlamydia and gonorrhea caused by Neisseria sp.).

So how does fusidic acid work against bacteria?

Fusidic acid, like chloramphenicol, can be simply considered as a ‘protein synthesis inhibitor’. The specific action of fusidic acid as a protein synthesis inhibitor is however quite different from that of chloramphenicol and the reason why the two drugs do not work on all the same bacteria. This difference in mechanism is also the reason why fusidic acid is only a narrow spectrum antibiotic while chloramphenicol is broad spectrum. Such drugs, if presented at adequate concentrations, should adversely affect the ability of some bacteria to make new proteins that are required for them to make copies of themselves and so be able to multiply at a fast rate. Like chloramphenicol, fusidic acid is generally considered to be bacteriostatic, i.e. it produces a stasis in the bacterial population.

 Fusidic acid is a true antibiotic in that it is produced by one microorganism and has antimicrobial effects on others. It was originally isolated in the early 1960’s from the fungus, Fusidium cocinium and belongs to a class of chemicals called fusidanes. It is an interesting chemical molecule because it has a structure with similarities to another type of antibiotic, cephalosporin P1 and also to a totally different drug, the glucocorticosteroid prednisolone.

The latter characteristic is rather important to fusidic acid since it means that it can penetrate into the ocular tissue in a similar way to the anti-inflammatory drug, although it does not have any obvious anti-inflammatory activity per se. This chemical resemblance to prednisolone is the reason why fusidic acid is sometimes referred to as a ‘steroid’ or even a ‘sterol’ antibiotic.

 In order for new protein synthesis to occur in bacteria, a sequence of steps in a complex mechanism needs to occur. The site of protein synthesis is on protein structures called ribosomes found in the cytoplasm of bacteria (Figure 5). In many commonly occurring bacteria, these very large globular proteins are organized into two aggregates of different size, nominally referred to as a larger 50 S subunit and a smaller 30 S subunit.

 The schematic given is that for a bacterium with a substantial cell wall, classified as a gram positive organism. An example would be Staphyloccus aureus. Gram negative organisms (e.g. Haemophilus influenzae or Pseudomonas aeruginosa) have similar overall organization but will have an additional outer membrane enclosing the cell wall (which is part of the reason why they does not take up the gram stain well).
 For both fusidic acid and chloramphenicol, the protein synthesis mechanism is based on the fact that newly formed proteins are made up of chains of amino acids. The assembly of these chains is carried out on a template that is made up of messenger RNA (mRNA for short) that is a sequence of nucleic acid bases (Figure 6).

These bases contain recognition sites that are composed of sequences of three, i.e. what are known as the ‘triplet codons’. During active protein synthesis, this mRNA template is closely associated with the ribosomes in the cytoplasm and, during active protein synthesis, these also have numerous other smaller proteins associated with them. The cytoplasm of the bacteria also contain soluble amino acids. Via a special set of biochemical reactions, individual amino acids become conjugated to another form of RNA, called peptidyl transfer RNA (tRNA) each of which has a unique triplet codon that will match with the sequence on the mRNA template.

Therefore, individual amino acids, are brought into the vicinity of the template by their respective tRNA carriers and, once the match it made, a series of biochemical, enzyme-based reactions serve to both separate the amino acid from its tRNA and to then link it to the amino acid chain being assembled on the ribosomes. These initial steps include a peptidyl transferase step that associates the incoming tRNA with the 50S subunit. Fusidic acid acts on the protein synthesis mechanism at a special step after this tRNA binding and transfer.

  There are actually two adjacent sites within the ribosome-mRNA complex, usually referred to as an A site and a P site. As the tRNA is initially presented to the ribosome it is bound at the A site, partly via the peptidyl transferase. However, as part of the process by which it will ultimately be linked to the poly-amino acid chain, the tRNA needs to be moved to the P site within the ribosome complex. This process is shown as the broad curved arrow on Figure 6 and is called translocation, and requires the activity of an enzyme complex called a translocase. This is one of the smaller proteins associated with the ribosomes during active protein synthesis. Fusidic acid acts as a protein synthesis inhibitor by binding to, and so stopping the activity of this translocase.

So, fusidic acid can be referred to as a translocation inhibitor and its effect can be substantial.  This is because the  dissociating peptidyl-tRNA cannot stay bound to the A site on the ribosome complex and if it cannot stay bound, then intra-ribosome peptide transfer does not occur and the assembly of the amino acid chain is simply interupted, so yielding a partial (and generally dysfunctional) peptide. There is some evidence that very high concentrations of fusidic acid may also block the initial binding of a peptidyl-tRNA into the ribosome-mRNA complex, but its main effect is as a translocase inhibitor.
 
How much fusidic acid is required to stop the replication of bacteria ?

In general terms, a useful antibiotic will readily affect susceptible bacteria at low concentrations and will produce an inhibitory effect fairly quickly. This would be expected for gram positive organsism such as Stapylococcus sp., but not all bacteria are susceptible to fusidic acid especially via the specific mechanism just described (Figure 6). In some cases, bacteria simply do not respond to the presence of fusidic acid even if massive amounts of the drug are used. This would be true resistance to fusidic acid, and can be characteristic of specific gram negative bacteria such as Pseudomonas sp. Alternatively, resistance to fusidic acid may be acquired, i.e. a bacterial type normally expected to be susceptible to fusidic acid develops resistance to ever increasing amounts of the drug.

This is a possible reason why quite a few bacterial types show what is called partial or intermediate sensitivity (susceptibility) to fusidic acid. An example here would be Haemophilus sp. associated with upper respiratory tract infections. This means that, in some cases, a substantial dose of fusidic acid may produce some slowing of bacterial growth, but this amount of the drug is not that which is routinely realized for long enough periods of time for the bacterium to be considered as susceptible.  Therefore, for fusidic acid, it is only low concentrations of the drug that can be expected to quickly exert a negative (inhibitory) effect on susceptible bacteria. This low concentration is determined in a clinical pathology lab, and is usually referred to as the Minimum Inhibitory Concentration or MIC. There are very specific guidelines on how an MIC should be determined and because of this the MIC value can be determined in microscopic amounts of g / mL .

 Such studies routinely indicate that commonly occurring Staphylococcus sp. (e.g. S. epidermidis and S. aureus) are likely to be susceptible to just 0.1 g / mL fusidic acid, and it can be noted that this concentration is readily realized at the ocular surface for a sustained period of time equivalent to that for which the MIC was determined, i.e. between 18 to 24 h. However, in marked contrast, the MIC for some other gram positive bacteria such as Streptococcus sp or gram negative bacteria such as Haemophilus sp., the MIC values can be expected to be some 100 X those needed to affect common Staphylococcus sp.

This sort of level of fusidic acid cannot be achieved at the ocular surface for sustained periods of time.  Overall, and in the short term (i.e. minutes to an hour or so), the uptake and binding of fusidic acid by susceptible bacteria, slows the net rate of protein synthesis. During protein synthesis, it is likely that multiple copies are normally made of a range of specific proteins that are needed for the bacterial division process to occur rapidly, and even a reduction in these will result in the replication rate being slightly slowed. If there is enough fusidic acid, the replication rate will be abruptly slowed or even stopped, although fusidic acid does not kill the bacteria. This means that fusidic acid, for susceptible bacteria, is generally considered to be bacteriostatic.

Overall, while some bacteria may also respond slowly to high concentrations of the fusidic acid, a decision has to made as to whether a bacterium would be expected to be routinely susceptible and within a reasonably short time period. The resultant strategy is to adopt what is called a ‘break point’ concentration. For fusidic acid, this is usually considered to be 1 g / mL and this would include all susceptible organisms.
 
The causes of bacterial conjunctivitis

It might often be presumed that bacterial conjunctivitis is caused by Staphylococcus organisms, and in a way this is true. However, this should not be presumed to be the case and this issue is especially important when in comes to considering the use of fusidic acid viscous eyedrops which are considered as “useful for Staphylococcus infections”.Since the advent of chemical anti-infective agents such as the sulphonamide (or ‘sulpha’) drugs and the first introduction of penicillin for local ophthalmic use in the 1950’s, clinicians have not only been interested in what organisms might cause bacterial conjunctivitis but also how responsive they might be to treatment. So, it is possible to find quite numerous studies where clinicians have taken samples of the discharge associated with a presumed bacterial conjunctivitis and submitted this to culture tests. An analysis of a  fair number of these reports over a  50 year period certainly confirms that it is not uncommon for Staphylococcal sp. to be the cause of a presumed bacterial conjunctivitis but that other bacteria can be encountered (FIGURE 7).

 Figure 7 shows that the most common isolate from patients with presumed bacterial conjunctivitis was the gram-positive Staphylococcus epidermidis . As presented in detail elsewhere,10 an average of 33.1 % of isolates from 25 different studies were identified as being S. epidermidis, while 26.0 % were reported to be the closely related S. aureus. In summary, therefore, Staphylococcus sp. can be considered as the most likely organism to be cultured from external eye swabs, likely accounting for around 2/3rd of isolates. However, amongst other gram-positive bacteria, Streptococcal sp. have been reported to account for an average of 17.1 % of aerobic isolates with the key microorganism being Streptococcus pneumoniae. Streptococcus sp., in general, are unlikely to be very sensitive to fusidic acid and are often associated with infections of the nasopharyngeal region (i.e. a ‘strep throat’ or PCF), the ears (otitis media, especially in infants and young children) or even the lungs (more especially, perhaps, in elderly patients). Some Streptococcus sp., even in young adults, can be very virulent and cause contagious epidemic conjunctivitis and can cause haemorrhaging of the conjunctiva. As part of the analyses, it was also considered useful to examine how often gram-negative bacteria might be associated with a presumed bacterial conjunctivitis and the result was a little surprising (Figure 7). 

As expected, Pseudomonas sp., principally Pseudomonas aeruginosa, is rarely associated with a diagnosis of bacterial conjunctivitis, with the average frequency of isolates being only 1.4 %. One can conclude therefore that it would be highly unusual for Pseudomonas to be the cause of a simple and uncomplicated conjunctivitis (with mucopurulent discharge) in non-contact lens wearers. The gram-negative organism that needs to be considered is however Haemophilus sp., notably H. influenzae or H. parainfluenzae.

These, as with many Streptococcus sp., associated with nasopharyngeal infections ad have been reported to account for an average of 14.6 % of ocular isolates in patients with conjunctivitis. This is important for, as with Streptococcus sp., Haemophilus sp. are also unlikely to be very sensitive to topical ocular treatment with fusidic acid. Both however are likely to be sensitive to chloramphenicol. Fusidic acid has no relevant activity against viral infections or Chlamydia.

So how should fusidic acid viscous eye drops be used and why ?

Since its introduction some 25 years ago, fusidic acid has routinely been presented to the external eye in the form of a viscous eye drop. It is commercially available as PoM Fucithalmic  viscous eye drops (Figure 8). UK optometrists may purchase the product from a pharmacy by routine ordering, but it is also available through bulk suppliers such as Mid-Optic.

 Alternatively, the optometrist may also access ophthalmic fusidic acid, for a named patient and via a pharmacist, by a written order, and pharmacists have been advised of this change in the law (although it might still be worth checking with your local pharmacy before you send a first patient down with a written order !).
 The viscosity is achieved by the formulation of the fusidic acid into a polyacrylic acid polymer vehicle now commonly known as a Carbomer  gel.

For the ophthalmic presentation, it is Carbomer 934P and this is designed to increase the residency time of the drug on the ocular surface and facilitate penetration of the drug into the cornea and conjunctiva. Pre-clinical studies using fusidic acid viscous eye drops or gels on rabbit eyes generally confirmed this expected effect, and there have been some human pharmacokinetic studies.10 Studies on human volunteers indicate that tear film levels of fusidic acid of perhaps 30 g / mL can be expected 1 h after a single drop instillation, perhaps 15 g / mL  after 3 h, 5 g after 6 h and with still some 1 to 3 g/mL even after 12 h !. Therefore, even at 12 h after administration, the levels of fusidic acid in the tears can be expected to be around the MIC break point of 1 g / mL for susceptible organisms such as S. aureus. This type of pharmacokinetic profile achieved with fusidic acid viscous eye drops is similar to that which can be achieved with an ointment form of an antibiotic.

The instillation of the viscous eye drops is best achieved by tilting the head back slightly, gently pulling the lower eyelid downwards, a single ‘drop’ application is then made into the lower conjunctival cul-de-sac and the eyes closed for about 30 s. Some patients, especially children, may find it difficult to keep their eyelids closed even for this short period of time. In such cases, eyelid closure may be facilitated by exerting gentle finger pressure across the eyelids or across the puncta of both eyes. There is some controversy on patient instructions for use of ophthalmic products. Some might wish to argue that after the instillation of the viscous eye drops, the patient should be instructed to blink a few times to facilitate distribution of the drug into the tear film and across the ocular surface. There is however no obvious pharmacokinetic data to support such a procedure, and so the present writers do not recommend this.

A standard dosing is twice-daily (bd) and the duration of the treatment should be for at least 5 days. However, if the condition is considered moderate or even severe, then there is no reason why the initial and ongoing treatment cannot be qds (i.e. every 4 h or so).  Similarly, there are no substantial reasons why treatment cannot be extended to 10 or even 14 days providing the condition is responding to treatment.  If substantial mucopurulent discharge is present, and especially in an infant or child, cleansing of the eye will likely improve the chance of a speedy resolution. There is no age limit specified for patients that can be treated with fusidic acid eye drops.
Details of any special instructions (e.g. cleansing of the eye), the initial dosing and the duration of treatment should be provided in writing to the patient if the optometrist is electing to supply the fusidic acid, and it might be prudent to include a reason for extended treatment if this is being undertaken. If a written order is being used, then these details should be on the supply and labeling instructions to the pharmacist, e.g. supply 1 tube fusidic acid viscous eye drops 1 % for twice daily use, both eyes, for 5 days. By default, Fucithalmic would be dispensed because there is no other product or generic available. The written order should also include details of the patient’s name, address and age, and be on stationary that clearly indicates the optometrist’s registered practice. Some have suggested that an optometrist could usefully include their GOC registration number on a written order.

The necessity of using the eye drops as indicated needs to be stressed to the patient (or their parent or guardian for paediatric cases), and that treatment should continue for 2 days after a ‘cure’ has been achieved. This recommendation applies even if the course of treatment was just 5 days. For a milder infection, a sufficient improvement may have occurred in just 3 days such that the patient considers that they no longer need to bother with using the viscous eye drops. Follow-up should be as appropriate, depending on the severity of the condition and the expected compliance of the patient. As a guideline, as the optometrist is directly or indirectly initiating the supply, the patient should be advised to return if the condition gets worse. This can be facilitated by providing the patient with a business card (or similar) with the practice telephone number. A patient will, in all likelihood, be prompted to seek further attention if the condition does not resolve in a few days, and so there is no formal requirement for a specific follow-up visit (e.g. at 48 hrs or after 5 days of treatment), providing the patient has been given an instructions as to when and where to seek further attention. This follows the same sort of procedures used in UK accident and emergency departments. Notwithstanding, there is no reason why an optometrist cannot choose to see a patient for a specified follow-up visit (e.g. at 48 h) if they feel that it is appropriate.

So on whom should fusidic acid viscous eye drops be used and why ?

The UK product is a 1 % viscous solution of fusidic acid in a 5 g tube. It is preserved with benzalkonium chloride. Almost no significant side effects have been reported with the routine use of the fusidic acid viscous eye drops for conjunctivitis, and most of these have been no more than some degree of discomfort. The MHRA / CSM Yellow Card reporting system indicates no major side effects from topical ocular fusidic acid over a 15 year period (since the general introduction of the product in the UK), but a current MIMS lists “irritation” as a possible adverse drug reaction (ADR). From this perspective, some studies have reported that fusidic acid was preferred to chloramphenicol eye ointment while other have indicated no difference or the opposite.   

 The indicated use for fusidic acid viscous eye drops in the UK, as opposed to the use of chloramphenicol products, might be for when allergy to the latter antibiotic (or the preservative in the eye rops) is suspected. Other uses, especially for the elderly, might be where it is considered that a better compliance over the recommended treatment period might be achieved with a twice-daily use of a viscous eye drop rather than use of chloramphenicol eye drops on at least a four times / day basis. While the dosing used in a range of clinical assessments of the product was twice-a-day, an initial dosing of four-times-a-day might be considered a prudent starting regimen, and was actually used in quite a few of the clinical efficacy studies. The same consideration of compliance and perhaps ease of administration might be given to treatment of bacterial conjunctivitis in children, but with special care taken to check that the infections are not associated with systemic infections of the respiratory tract or ears. In all cases, the optometrist should assume responsibility for patient care and follow up. With the indicated use, no cultures will be taken and a correct differential diagnosis of conjunctivitis versus keratitis is important. For any patient in whom some positive response to treatment is not evident with 24 to 48 h, consideration should be given to their seeking a medical opinion.

 Over a 15 year period, various clinical trials have been reported on the use of fusidic acid viscous eye drops as part of the management of bacterial conjunctivitis. In many such trials, a ‘bacterial conjunctivitis’ was simply the presumed cause of the presenting condition and there were few other tests carried out. So too, therefore, the UK optometrist can start the use of fusidic acid viscous eye drops on the basis of a presumed diagnosis (Table 1). Overall, such clinical studies indicate that 9 out of 10 cases where susceptible bacteria are the cause of the conjunctivitis, a favorable outcome would be expected. No obvious differences in outcome, providing susceptible bacteria were the cause, can be predicted when comparing infants with adults or with the elderly (assuming that the drops were used properly and for the specified period of time). The true incidence of full resistance to fusidic acid is likely less than 5 % when bacterial conjunctivitis is the condition being treated. However, when cases of keratitis (and corneal ulcers) are being considered, then the resistance to fusidic acid may be anywhere between  40 and 60 %.

 In addition to its use for presumed bacterial conjunctivitis, fusidic acid has unlabelled uses for management of corneal and conjunctival abrasions or foreign bodies, as well as for some cases of blepharitis (or blepharoconjunctivitis). Single applications of fusidic acid viscous eye drops (perhaps followed by eye closure and application of a light compress patch with tape to keep the eye shut for 24 h), have been reported to have equivalent efficacy to the same type of use of chloramphenicol eye ointment. Such management should also include a cycloplegic (e.g. cyclopentolate 1 % eye drops applied 5 min before the antibiotic). The instillation of the viscous eye drops, in itself, may improve marginal bacterial infections including blepharoconjunctivitis and blepharitis. Whilst the eye drops are instilled into the low cul-de-sac, providing there is adequate retention of the eye drops (e.g. by eyelid closure for a reasonable period of time), then the viscous antibiotic solution would be expected to seep out and coat the marginal zone of the eyelids and even get around the bases of the eyelashes.The management of blepharitis is likely to be better accomplished not only with the use of the viscous eye drops on a four times daily (QDS) regimen but also with lid hygiene (lid scrub) measures.  
 
 
References
1. Statutory Instrument 2005 No. 764. MEDICINES. The Medicines (Sale or Supply) (Miscellaneous Provisions) Amendment Regulations 2005.
2. Statutory Instrument 2005 No. 765. MEDICINES. The Medicines for Human Use (Prescribing) Prescribing Order 2005.
3. Statutory Instrument 2005 No. 766. MEDICINES. The Medicines (Pharmacy and General Sale - Exemption) Amendment Order 2005.
4. Seal DV, Barrett SP, McGill JI (1982) Aetiology and treatment of acute bacterial infection of the external eye. Br J Ophthalmol 66:357-360.
5. Rietveld, R.P., Terriet, G., Bindels, P.J.E., Sloos, J.H. and Van Weert, M.C.P.M. (2004). Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms. Br Med J 329:206-210.
6. Johnson ME (2005) Chloramphenicol for the treatment of acute bacterial conjunctivitis. Optician 230 (no. 6025): 26-32.
7. Doughty MJ (2005) Drugs, Medications and the Eye. 14th Edn. Smawcastellane Information Services, Helensburgh G84 7HL.
8. Andrews, J.M. (2001) Determination of minimum inhibitory concentrations; BSAC standardized disc susceptibility testing method.  J Antimicrob Chemotherap 48 (suppl. S1), 5-16, 43-57.
9. British National Formulary (BNF) (2006) British Medical Association, and Royal Pharmaceutical Society of Great Britain. Volume 51, pp. 534-536.
10. Doughty MJ, Dutton GN (2006) Fusidic acid viscous eyedrops - an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK optometrists. Ophthal Physiol Optics – in press.
11. Kanski JJ (1999) Clinical Ophthalmology, 4th Edn. Butterworth-Heinemann, Oxford.
12. Hashemi K, Chuang AZ, Schweitzer C, Lanier JD (2000) Comparison of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin. Cornea 19: 459-463.

Providing exclusive eye care news, information and educational needs every week, including a FREE CET programme. Subscribe to Optician Print Edition.