Preservatives in eye
There are several
antimicrobial preservatives used in ocular preparations that may be
classified as follows:
First they may be
divided into two types: chemical and oxidative.
I. Main Chemical Preservatives:
Chemical preservatives alter cell membrane
permeability and lyse (divide) cytoplasmic
ammoniums, surfactant and disinfectant agents, among which are
benzalkonium chloride, cetremide or cetrimonium
chloride or bromide, benzododecinium bromide, miramine,
cetylpyridinium chloride, polidronium chloride or polyquarternium-1, polyquaternium-42
(also known as polexitonium), sepazonium, etc
derivatives such as the phenylmercury salts (acetate, borate or
nitrate), mercuriothiolate sodium (otherwise called thiomersal or
thimerosal) and mercurobutol
such as chlorhexidine digluconate or polyhexamethylene biguanide (PHMB)
such as chlorobutanol or phenylethanol, phenoxyethanol
or esters such as parahydroxybenzoic acid,
II. Oxidative Preservatives
Oxidative preservatives are able to penetrate cell membranes and
interfere with a cell’s functions.
Sodium perborate or GenAqua®
which works by oxidizing cell's
membranes and disrupting cellular function. When combined with water,
sodium perborate is converted to hydrogen peroxide, thus
In contact with the tear film, it
converts itself into oxygen and water molecules.
Stabilized oxychloro complex (SOC)
is a compound usually used for water
oxyborate complex or Dissipate™
Anti-Oxidant Preservative and other complexes having a preservative
(EDTA, (di)sodium edetate)
Sodium silver chloride complex
and silver sulfate
Sorbate (sorbic acid)
many preservatives have synonyms and several commercial/trademark names:
Synonyms for BAK: parasterol, alkyl benzyl dimethylammonium chloride,
alkyl dimethyl benzylammonium chloride, benirol, cequartryl, drapolene,
enuclene, germitol, gesminol, rodalon, ammonyx, zephiran chloride,
[various further trade names… but best known as Benzalkonium chloride.]
Synonyms for EDTA: H4EDTA,
Versene, ethylenedinitrilotetraacetic or
ethylenediaminetetraacetic acid, Diaminoethanetetraacetic
acid, N, N ' - 1 , 2 - ethanediylbis (N-(carboxymethyl)
(glycine) edetic acid, ethylenedinitrilotetracetatic acid, celon A,
gluma cleanser, nervanaid B acid, nullapon B acid, sequestrene AA,
tetrine acid, titriplex, trilon BS, versene acid, vinkeil 100,
warkeelate acid, YD 30, edetate (di or tri) sodium, and
various further trade names… but best known as
EDTA. It’s "Funny" to notice that EDTA is mentioned as an
eye-irritant by several manufacturers of the product for many
Synonym for Cetremide:
cetrimonium bromide or
Synonyms for sodium
chlorite: Purite® or stabilized oxychloro complex (SOC)
Synonyms for sodium
perborate: PBS or GenAqua®.
polidronium chloride: polyquarternium-1 or
Synomyms for polexitonium:
polyquarternium 42 or Busan 1507
are preservatives for? Do preservatives really
play their safety role? Why are they used then?
Preservative are added to
preserve eyedrops to ensure the sterility over the course of several
weeks and sometimes months (usually less than a month). So they're not
there to prevent infection in the eye but just to maintain sterility of
the bottle against microbes (viruses, bacteria, and fungi
or molds.. But are they really effective in doing so?
Some studies indicate that
preservative do not protect agains all type of possible contamination of
the bottle. Quartenary ammoniums have a limited efficacy against some
gram positive and negative bacteria but particluarly against some mould
spores such as mycobacteria and clostridium for instance[1,2].
One study found that 29%
of solutions were contaminated by micro-organisms. Another study done
in ophthalmic consultations services and in a home for the elderly [though
usually trained in hygienic measures], demonstrated that 16,3 %
of all bottles were contaminated,
including 5,4 % very severely
Another study on
a broad range of preservatives, concluded that only the combination of
Benzalkonium and EDTA was able to meet the safety criteria for European
Pharmacopoeia. But this combination is also one of the worst for the
eye's heatlh (see
What are the consequences?)
. So long term efficacy seems to be a chimera if not a dangerous
illusion leading to increased accidents. Since preserved bottles suppose
many instillations, the risk is increased and usually the tip if
infected due to improper use or some kind of contact with any
contaminating surface (eye or finger for instance). With single use
vials such problem does not exist.
You may find a very broad
spectrum of litterature on this subject, particularly on contact
lenses-related solutions and the CLARE syndrome.
Benzalkonium chloride: failures as an antiseptic,
JAMA,1976 Nov 22;236(21):2433
2. Conservateurs et
Surface Oculaire, Quelques bonnes raisons pour abandonner l'utilisation
des collyres conservés. Dr. Magda de Saint-Jean, Pr. Christophe
Baudouin, Librairie Médical Théa.
Microbial contamination of in-use
ocular medications, O. D. Schein, P. L. Hibberd,
T. Starck, A. S. Baker and K. R. Kenyon,
Dana Center for Preventive Ophthalmology, Wilmer
Institute, Johns Hopkins University, Baltimore, Md 21205.
PMID: 1731727 [PubMed - indexed for MEDLINE]
Are Multidose Over-the-Counter Artificial Tears
Charnock, Colin PhD,
Cornea. 25(4):432-437, May 2006.
5. Etude de la contamination bactérienne
de collyres en usage clinique (Bacterial contamination study of in-use
eyedrops), Raynaud C., Rigal D., Bonicel P, Service d'Ophtalmologie, CHU
G. Montpied, BP 69, 63000 Clermont-Ferrand, FRANCE & Laveran H, Service
d'Hygiène Hospitalière, Université d'Auvergne Clermont-Ferrand I, BP
38, 63000 Clermont-Ferrant, FRANCE.
This is what we call the 'Preservative Paradox!
our Eyes, not our Drops!