|
Category /Preservative |
Consequence |
Source
(see bellow) |
| All Quaternary ammoniums (including
BAK) |
Contact Allergy/Eczema (Type IV delayed
hypersensivitivy) in 4 to 11% of patch tests for BAK |
1 ; 2 ; 5 ; 6 ; 9 ; 10 |
| Benzalkonium Chloride
(BAK or BAC) |
Disruption of the tear film ;
soap effect in contact with the lipid layer of the tear film |
1 ; 2 ; 6 ; 13 ; 26 |
| Dissecating effect;
Dryness, Reduced tear secretion |
1 ; 2; 8 ; 19 |
| Cytotoxic (in general) |
1 ; 16 ; 17 |
| Pseudo-pemphigoïd (rare) ;
Sub-epithelial fibrosis |
8 ; |
| Delayed Healing |
14 ; |
| Epithelial denegeneration;
Cessation of normal cell mitotic activity ; reduced cytokinesis
|
17 ; 2 |
| Cell exfoliation, abrasion,
cell lysis; desquamation |
11 ; 18 |
| All cells died in 24
hours at 0.1% concentration but reported cell death in concentration
as low as 0.0001 % |
21 ; |
| corneal and conjunctival damage,
epithelial alterations, various degrees of keratinization,
limbal inflammatory infiltrates and within the conjunctival
stroma and epithelium |
22 |
| short-term exposure can alter the
precorneal mucin |
27 |
| Cetremide
or Cetrimonium Chloride |
corneal and conjunctival damage,
epithelial alterations, various degrees of keratinization,
limbal inflammatory infiltrates and within the conjunctival
stroma and epithelium |
22 |
| Benzododecinium
Bromide |
corneal and conjunctival damage,
epithelial alterations, various degrees of keratinization,
limbal inflammatory infiltrates and within the conjunctival
stroma and epithelium |
22 |
| Polexitonium (polyquarternium-
42) |
"very
low toxicity" |
28* |
| Mercurial
Derivatives (particularly Thiomersal or Thimerosal) |
Delayed Allergy (Type IV) in 13
to 37% of patch tests. |
9 |
| Thiomersal or
Thimerosal |
Severe allergic reaction;
irritation |
1 ; 2 |
| Penetration of the
tissue: Greyish Coloration of the Lens (Iatrogenic
Catact/mercurial impregnation)/ detectable in several eye
tissues |
1 ; 23 |
| Band Keratitis, superficial
keratitis |
1 ; |
| Cytotoxic (including enlarged
inter-cells space ; reduction of natural surface microvillosities) |
1 ; 9 ; 11 |
| Increased Permeability in Dry Eye
Patients |
12 |
| Modification of corneal
endothelial cells |
15 |
| Cell lysis;
Desquamation |
9 |
| Corneal
and conjunctival damage, epithelial alterations, various degrees of
keratinization, limbal inflammatory
infiltrates and within the conjunctival stroma and epithelium |
22 |
| Amidines (including
Chlorhexidine) |
|
|
| Chlorhexidine |
Hypersensitivity (allergy) in
contact lens wearers |
1 ; 7 |
| Cell lysis;
Desquamation |
9 |
| Accumulation in
corneal and conjonctival epithelial cells |
2 |
| Alcohols |
|
|
| Chlorobutanol |
Cytotoxicity: including
Epithelial denegeneration; Cessation of normal cell mitotic activity
; reduced cytokinesis |
17 ; |
| Cell exfoliation ; abrasion |
18 ; |
| Irritation in over 50% of
patients |
20 ; |
| Increased Permeability in Dry Eye
Patients |
12 |
| Increased
evaporation |
2 |
| Parabens |
|
|
| Methylparahydroxybenzoate |
Corneal
and conjunctival damage, epithelial alterations, various degrees of
keratinization, limbal inflammatory
infiltrates and within the conjunctival stroma and epithelium |
22 ; |
| Other
Preservatives |
|
|
| EDTA (or Na2EDTA, ededate
disodium) |
Modification of corneal
endothelial cells |
15 ; |
| PBS |
corneal and conjunctival damage,
epithelial alterations, various degrees of keratinization,
limbal inflammatory infiltrates and within the conjunctival
stroma and epithelium |
22 ; |
Studies (some studies' abstracts may be available at
Pubmed)
1: Les Conservateurs en
Ophtalmologie, Docteur Patrice Vo Tan, Docteur Yves Lachkar, Librairie
Médicale Théa, 64 pages.
2: American
Optometric Association. Care of the patient with ocular surface
disorders. St. Louis (MO): American Optometric Association.
3:
Comparative study of topical anti-allergic eye drops on human
conjunctiva-derived cells: responses to histamine and IFN
gamma and toxicological profiles
Pauly A,
Brignole-Baudouin
F,
Guenoun JM,
Riancho L,
Rat P,
Warnet JM,
Baudouin C.
U598, INSERM, Cordeliers Biomedical Institute, 15 rue de l'ecole de
medecine, 75006, Paris, France. CONCLUSIONS: The
ability of topical ocular anti-H(1) drugs to significantly reduce the
production of IL-6 and IL-8 argues that they may help treat the
inflammatory processes occurring in allergic ocular surface disorders.
Nevertheless, preserved ophthalmic formulations may enhance epithelial
conjunctival expression of ICAM-1 in the presence of a low inflammatory
stimulus, such as IFNgamma, and displayed toxic as well as pro-oxidative
effects on these cells. Therefore, BAC used as preservative might in
part interfere with the potential anti-inflammatory properties of the
active compound by modulating the immuno-inflammatory response of
epithelial conjunctival cells. To
display study click here
4: A
comparative study of the ocular tolerance after administration of
anti-allergic eye drops with or without a preservative. [Article in
French] ,
Beden C, Helleboid L, Marmouz F, Liard F. Societe Naxis, Lyon, France.
CONCLUSION: The prescription of eye drops with no preservative allows a
significant decrease in ocular adverse drug reactions and a greater
acceptance by the patient regarding his/her anti-allergic treatment.
5: Ophtalmologie et allergie cutanée, OPA Pratique, Castelain M & PY, 1991, 50, 1-4.
6: Que faire des malades allergiques au benzalkonium? Verin, Casamayor, Coulon, Williamson, Mortemousque, Ndiyae Pa, Bull.
Soc. Ophtalmol. Fr., 1992, 33, 7, 2233-2241.
7: Ocular inflammation in patients using soft
contact lens solution, Rietschel, Wilson, Arch. Dermatol., 1982,
118, 3, 147-149.
8: ß-Bloquants et
conservateurs, Pr. Christophe Baudouin, Centre Hospitalier d'Ophtalomologie
des Quinze-Vingts et INSERM U-598, Paris, Visions partagées - April
2004.
9: Allergie, Collyres et
conservateurs: rappels, B. mortemousque et Ph. Vérin, CHU Hôpitaux de
Bordeaux, Librairie Médicale Théa, n°2.
10: Patch testing in ocular drug
allergies, Marsh, Towns, Evans, Trans. Ophthalmol. Soc UK, 1978, 98, 2
278-280.
11: Quantitative
cytotoxicity of preservatives evaluated in cell culture with Chang's
human conjunctival cells--effect of temperature on cytotoxicity.
n. Takahashi, Jpn. Journal of Ophthalmol.
1982;26(2):234-8
12: Corneal
epithelial permeability of dry eyes before and after treatment with
artificial tears, Göbbels, Spitznas, University
Eye Hospital, Bonn, Germany, Ophthalmology,
1992 June;
99(6):873-8.
13:
Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man.
WS Wilson, AJ Duncan and JL Jay. 1975 by the British Journal of Ophthalmology.
14:
The effect of ophthalmic preservatives on the
healing rate of the rabbit corneal epithelium after keratectomy,
American Journal of Ophthalmology, Collin, Grabsch,
1982 Mar;59(3):215-22.
15: The effect of ophthalmic
preservatives on the shape of corneal endothelial cells.
Collin, Grabsch, Acta
Ophthalmol. Copenhague, 1982 Feb;60(1):93-105.PMID:
6182733 [PubMed - indexed for MEDLINE]
16:
A new method evaluating quantitative
time-dependent cytotoxicity of ophthalmic solutions in cell culture.
Beta-adrenergic blocking agents, Nobuo Takahashi,
Department of
Ophthalmology, Kanazawa Medical University, Uchinadamachi 1-1, Kahoku
gun, 920-02 Ishikawa, Japan,
Graefe's Archive for Clinical and Experimental Ophthalmology.
17:
Cytotoxic effects of
benzalkonium chloride and chlorobutanol on human corneal epithelial
cells in vitro., Tripathi BJ & RC, Eye Research
Laboratories, University of Chicago, IL 60637,
Lens Eye Toxic Research,
1989;6(3):395-403. PMID: 2486935 [PubMed -
indexed for MEDLINE]
18:
Acute effects of chlorobutanol- or benzalkonium
chloride-containing artificial tears on the surface features of rabbit
corneal epithelial cells, Doughty MJ, School of
Optometry, University of Waterloo, Ontario, Canada,
Optometric Vision Sc.
1994 Sep;71(9):562-72.
[PMID: 7816427 [PubMed - indexed for MEDLINE]
19:
Adverse effects of topical antiglaucomatous
medications on the conjunctiva and the lachrymal response,
R. Nuzzi1, C. Finazzo1 and A. Cerruti1,
Institute
of Ophthalmology, University of Turin, Italy,
International Ophthalmology.
20:
Irritation associated
with tear-replacement ophthalmic drops. A pharmaceutical and subjective
investigation.
Fassihi AR, Naidoo NT. S Afr Med J
1989;75:233-235. PMID:
2648609 [PubMed - indexed for MEDLINE]
21:
Effects of benzalkonium chloride on growth and survival of Chang
conjunctival cells. De Saint Jean M, Brignole F, Bringuier AF, Bauchet
A, Feldman G, Baudouin C. Invest Ophthalmol Vis Sci 1999;40:3:619-30.
22:
Histopathological effects of topical ophthalmic preservatives on the rat
corneoconjunctival surface. Becquet F, Goldschild M, Moldovan MS,
Ettaiche M, Gastaud P, Baudouin C. Current
Eye Research 1998;17:4:419-25.
PMID: 9561834
[PubMed - indexed for MEDLINE]
23. Conservateurs et
Surface Oculaire, Quelques bonnes raisons pour abandonner l'utilisation
des collyres conservés. Dr. Magda de Saint-Jean, Pr. Christophe
Baudouin, Hôpital Ambroise Paré, Librairie Médical Théa.
24.
Comparison of
toxicological profiles of benzalkonium chloride and polyquaternium-1: an
experimental study. Labbe A, Pauly A, Liang H,
Brignole-Baudouin F, Martin C, Warnet JM,
Baudouin C. Department of Ophthalmology III, Quinze-Vingts National
Ophthalmology Hospital, and INSERM U598, Cordeliers Biomedical
Institute, University of Paris 5, Paris, France.
PMID: 16910868,
J Ocul Pharmacol Ther. 2006 Aug;22(4):267-78
[PubMed - indexed for MEDLINE]
25.
Quantitative evaluation of the corneal epithelial
barrier: effect of artificial tears and preservatives,
Lopez
Bernal D, Ubels JL.
Department of Ophthalmology, Medical
College of Wisconsin, Milwaukee 53226,
Curr Eye Res.
1991 Jul;10(7):645-56.
PMID:
1914501 [PubMed - indexed for MEDLINE]
26.
How the most common preservative affects the
Meibomian lipid layer, Kaercher T.; Hönig D.; Barth
W., Orbit, Volume 18, Number 2, June 1999, pp.
89-97(9), Taylor & Francis Ltd.
27.
Impact of
short-term exposure of commercial eyedrops preserved with benzalkonium
chloride on precorneal mucin, Chung SH, Lee SK, Cristol SM, Lee ES, Lee
DW, SEO KY, Kim EK, Institute of Vision Research,
Department of Ophthalmology, Yonsei University College of Medicine,
Seoul, Korea.
Mol Vis.
2006 Apr 26;12:415-21
PMID: 16688112 [PubMed - indexed for MEDLINE]
28.
*No published studies to
date address the toxicity and surface consequences of polexitonium, to
our current knowledge only the Draize test was carried out, which does
not warrant total safety of this new preservative. Further independent
testing is nedeed in our opinion for use in therapeutic eye drops.
However, there are
Reference on polexitonium, including " Contact Lenses Solutions...making
sense of the multitude, Fiona Flynn-Smith". Remember that safety
criteria for contact lens use, which are made for healthy eyes is
different from safety for unhealthy corneas (contact lens may require
sterile saline cleansing of the lenses before wear and therefore the
toxicity of the preservative can be avoided). One manufacturer/ reseller
mentions clinical studies at
http://www.dryeyezone.com/encyclopedia/busan1507.html but does not
provide further indications on safety data. Another manufacturer claims
that "FreshKote®
has a unique preservative that is not only harmless to the eye but also
makes the ocular surface more wettable, just the opposite of what some
other preservatives do"
in the following webpage
http://www.freshkote.com/FAQ.asp.
We did not focus that
much on immediate allergy (Type I) since all molecules involved here and
even the active substance is likely to cause this type of allergy.
However, this consequence is easy to recognise and is usually quickly
solved by avoidance of the product. However, let's not forget that
removal isn't the solution for the underlying cause for the treatment.
If the étiology of the allergy is the preservative then the solution is
a preservative-free version of the product... if it exists. 