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Antimicrobial surfaces and materials for contact lenses and lens cases.

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  • Maastricht University | University of Buraimi

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ANTI-MICROBIAL SURFACES AND MATERIALS FOR CONTACT LENSES & LENS CASES: THE
FUTURE & CHALLENGES
Babu Noushad (M.Optom, FLVPEI, FIACLE)
Department of Optometry, Manipal College of Allied Health Sciences, Manipal
University, Manipal
BACKGROUND
Advancements in the contact lens (CL) and lens care technologies during the past few
decades have contributed significantly to the safety and efficacy of lens wear, making
contact lenses an option for more patients than ever before. In fact, it is estimated that
over 125million people worldwide are wearing contact lenses and over 90% of them are
using some form of soft contact lenses1. In India, the contact lens usage has increased
significantly for the last 5 years and is expected to grow at 20% per annum.
However, despite the improvements in contact lens materials and the effectiveness of
new lens care solutions, some patients still experience lens related adverse responses.
The use of contact lenses is known to increase the microbial load in the eye which can
adversely affect the corneal health2. The harmful impact can range from a mild ocular
redness and irritation to a very severe sight threatening situation like
Acanthamoeba
keratitis3. Poor contact lens hygiene and microbial contamination of the lens storage
case have been observed to be significant risk factors for contact lens related microbial
keratitis4.
In developed countries, contact lens wear, specifically extended wear with hydrogel
lenses, overrides all other risk factors for the development of microbial keratitis in
otherwise healthy eyes2. The presence of the CL influences development of infection
as the lens biomaterial acts as a vector for adherence of microorganisms with
subsequent transfer to the ocular surface. Epidemiological studies of contact lens wear
over the past 20 years have shown that there remains an almost constant rate of
microbial keratitis associated with lens wear; 2-4/10,000 wearers per year if lenses are
worn on a daily wear schedule and 20-26/10,000 wearers per year if worn on an
extended wear (i.e. sleep in lenses) schedule5. Furthermore, contact lens wear is
associated with other non-infectious forms of keratitis including contact lens induced
acute red eye (CLARE) and contact lens induced peripheral ulcers (CLPU)6. Holden et al.7
have hypothesized that endotoxin released from gram-negative bacteria is a primary
cause of the cellular response and infiltration seen when CLs are highly contaminated
with gram-negative bacteria. However the pathway between bacterial contamination of
CLs and corneal inflammatory events is not as straightforward as the link between CL
bioburden and microbial keratitis. There are many other speculative causes of
inflammation (lens deposits or defects, hypoxia, cytotoxicity of care solutions, changes
in pH and oxygen & CO2 concentration and corneal surface disruption), which may be
present alone or in combination with lens bioburden. Even so, most research has been
applied to microbial colonization of CLs as it seems to be the most consistent and
repeatable finding and has biologic plausibility.
MICROBIAL CONTAMINATION: LENSES Vs CASES
The frequency of storage case contamination is higher than associated lens
contamination (fig1). Studies have documented contamination rate as high as 81% on
storage cases8-11. Assessment of biofilm formed on lenses and lens cases on patients
with microbial keratitis revealed that the frequency of contamination and biofilm
density was significantly higher on cases than on lens12. Unlike lens contamination,
which is almost exclusively bacterial, when contamination is detected within solution
found in lens cases or on the internal wells, the microorganisms involved are usually
mixed contaminants of bacteria, fungi, and protozoa8-9.
On the other hand, during normal CL wear, the incidence of microbial bioburden on
traditional hydrophilic or SiH CLs is approximately 55% to 85%. But, the isolated
organisms were majorly bacteria and are mostly considered normal microbiota13-14.
Although Gram negative and other pathogenic organisms were also present, they are
found much more sporadically and in a smaller percentage. This highlights the potency
of the ocular defense mechanism. These defense mechanisms include blinking (which
mechanically removes loosely adherent organisms); immunoproteins and mucin, which
kill or inhibit organisms; and normal ocular flora, which inhibit the growth of
pathogens by consuming nutrients and secreting antimicrobial toxins. A common
misperception is that microbial bioburden increases gradually on lenses over time.
Studies have shown that there is no increase in the colonization of lenses by potential
pathogens or normal flora with length of wear or age of lens15. However, there are
contradicting reports in terms of bioburden on Hydrogel & SiH lens materials16-17.
(a)
(b)
Fig 1:(a) A biofilm on a contact lens, with clumps of cocci and sparse rods, while the
lens case from the same patient (b) has a similar but more extensive biofilm
These findings are giving an insight to the way the user should take care of lens
storage cases as its contamination causes the transfer of organisms to the lens surface
and ultimately to the ocular surface.
BIOFILMS
In this context, it would be interesting to understand a bit more about biofilms. Biofilm
is an aggregate of microorganisms in which cells are stuck to each other or to a
surface or to both. These adherent cells are frequently embedded within a self-
produced matrix of extracellular polymeric substance (‘outer shell’ or Glycocalyx). The
cells of a microorganism growing in a biofilm are physiologically distinct from
planktonic cells of the same organism, which by contrast, are single cells that may
float or swim in a liquid medium (Definition from Wikipedia). The outer shell protects
pathogens on the inside while continuing to recruit free-floating microorganisms. The
cycle continues as the biofilm matrix becomes larger, making this complex network of
microorganisms more difficult to kill18.
We also know that the growth of biofilm formation occurs rapidly over the initial two
hours for
S. marcescens
and six hours for
P. aeruginosa
19. These become the anchor
cells, making it easy for other cells to adhere. At this “infant” stage, the biofilm is easy
to eradicate because of its loosely connected network of cells. But, once other cells
build upon the anchor cells, adherence between them and the contact lens case or lens
surface becomes stronger. The mature biofilm begins to produce a substance that has
new properties, making it more antimicrobial resistant than individual planktonic cells.
ANTIMICROBIAL SURFACES FOR LENSES & LENS CASES: IMPORTANCE
There are numerous sources of potentially harmful organisms exist in the realm of
contact lenses, including the hands and ocular adnexa of the wearer, lenses, lens
cases, and water. Eye care practitioners and their staff spend much time and effort
educating patients on proper personal hygiene, lens wear, and lens care practices to
avoid contamination with infecting agents. Unfortunately, all of those steps require the
patient to actively comply with proper instructions. Thus, prevention of lens and
storage case microbial contamination is desirable even for compliant patients who use
modern care systems. Preventing bacterial adhesion would limit biofilm formation,
which could help prevent infection and inflammation. One potential method for
preventing bacterial adhesion is the use of antimicrobial agents, which have been used
in the medical field for decades. Antimicrobial agents have been used for a wide range
of products including orthopedic implants, urinary catheters, spinal shunts and wound
dressings, to name a few. Currently, researchers are exploring the option of using
antimicrobial surfaces and materials for contact lenses to further improve their safety.
A wide variety of antimicrobial technologies could potentially be employed for use with
a contact lens. Some may be applied to the surface of the lens material, while others
may be infused directly into the lens polymer. Regardless of how it is created, the goal
of an antimicrobial lens is to reduce or eliminate adverse events caused by infective
agents. An ideal “antimicrobial lens” would be, among other things, non-toxic to the
human cornea and other tissues, would provide broad-spectrum antimicrobial activity,
and would have minimal impact on the normal ocular flora.
POSSIBLE ANTIMICROBIAL TECHNOLOGIES FOR USE IN CONTACT LENSES
Researchers are currently investigating several antimicrobial surface technologies for
use in the medical field. However, a limited amount of information is published on the
use of these agents applied to contact lenses and lens cases
Silver
Silver is a broad-spectrum antimicrobial agent with low toxicity to human tissue when
used at therapeutic levels. It has been used since the 19th century to treat infections,
and silver nitrate is still used to prevent neonatal ocular infections. Silver retards the
adherence and colonization of microorganisms through its many mechanisms of
action, including interference with DNA and RNA to inhibit replication, disruption of
the cell membrane, interference with cell respiration, and inactivation and alteration of
enzyme conformation. It is unlikely that specific bacterial strains could undergo
simultaneous mutations to multiple mechanisms to develop resistance to the broad
scope of action of silver. To date, no resistant strains have been encountered clinically.
Slow release of silver ions from the impregnated silver when it comes in contact with
the solution provides the antibacterial property.
Fig 3: Silver impregnated lens case works by slowly releasing silver ions into the
solution to maintain an antibacterial surface.
In vitro studies have shown the efficacy of silver impregnated case against several
strains of bacteria, including
Pseudomonas aeruginosa
and a significant 40% reduction
in the incidence of bacterial lens case contamination23. A very recent study has
observed a considerable difference in the antimicrobial capacity of 3 different contact
lens cases impregnated with silver24. The amount of silver released by each cases as
well as its antimicrobial activity against various strains of organisms were also different
during the study duration. Further studies are in progress with silver-impregnated
cases in conjunction with multipurpose solutions and CLs to better model the in vivo
situation. Futhermore, Silver-coated contact lenses have been tested in the laboratory
and shown to be effective at reducing the colonization by
Pseudomonas aeruginosa
but not as effective against
Staphylococcus
25. Recently, hydrogel lens (etafilcon-A)
impregnated with silver nano-particles have shown that silver can prevent colonization
of the lens surface by a strain of
P. aeruginosa
,
S. aureus
and
Acanthamoeba
26.
Antibacterial lens case available in western market: Currently there are 3 types of flat-
bottomed cases are available and all are impregnated with silver.
1. MicroBlock Antimicrobial lens case (CIBA Vision, Atlanta, GA): The antimicrobial
activity of MicroBlock is achieved by a glass powder additive that releases silver
ions in the presence of moisture through ion exchange. The additive is
incorporated during the injection moulding process and is present throughout
the whole thickness of the plastic. It cannot be worn away and is effective on
both the inside and outside of the case.
2. i-clean Antibacterial lens case (Sauflon Pharmaceuticals Ltd., London, UK)
3. Nano-Case (Marietta Vision, Marietta, GA)
Polyquats
Polymeric quaternary ammonium compounds (polyquats) are another option. They are
commonly used as disinfectants and preservatives, and algaecides for pools and hot
tubs. Polyquats have also been used in contact lens solutions as disinfectants and
preservatives. Their efficacy in contact lens solutions is primarily caused by chelation
of bacterial components with the compound. More recently, these compounds have
been used in dental fillings, catheters, and polymers used in contact lenses to reduce
bacterial biofilm formation and adherence to the surfaces of the devices27.
Polymeric Pyridinium Compounds
Polymeric pyridinium compounds have a broad spectrum of antimicrobial activity and
can be covalently bound to surfaces. Upon contact with bacteria, the long amphipathic
polycationic chains penetrate the bacterial cell wall. It has been observed that these
compounds were active against a broad spectrum of microorganisms and that they did
not leach from the surface and thus would not be depleted with time. Researchers have
found that they can be applied to contact lens polymers27.
Free Radical Producing Agents
Free radical-producing agents, such as selenium compounds and nitric oxide-
releasing polymers, have been used for antimicrobial coatings as well. Selenium
compounds can generate superoxide free radicals which can oxidize bacterial cells and
prohibit cell growth. In 2006, Mathews and colleagues published the results of a study
investigating silicone hydrogel contact lenses with covalently bonded selenium in a
rabbit model28. These lenses demonstrated resistance to
P. aeruginosa
colonization
in
vitro
. Additionally, after two months of extended wear, corneal health was not
adversely affected by the selenium-coated silicone hydrogel contact lenses.
Quorum-Sensing Blockers
Quorum-sensing compounds are another class of agents with potential for use in
antimicrobial coatings. The ability of microorganisms to communicate with each other
and coordinate behavior is called quorum sensing. Subsequently, Quorum-sensing
compounds inhibit bacteria by interfering with their signaling systems. Furanones (one
example of quorum sensing compounds) are agents that occur naturally in red algae
and prevent bacteria from colonizing on the algae’s surface. The antimicrobial effect of
adsorbed synthetic furanones on medical device polymers has been studied29 Baveja
and colleagues, have reported that a furanone-coated material significantly reduced
S.
epidermidis
bacterial load on the polymer and slime production, while having no
significant effect on the substrate’s material characteristics. The use of furanones to
coat contact lenses has also been studied. In one study, contact lenses were soaked in
synthetic furanone, but the study results were unclear30.
Anti-infective Agents
Anti-infective agents are a different class of agents that kill infectious organisms or
prevent them from spreading and causing infection. The human body has potent anti-
infectives that naturally occur from neutrophils and macrophages called “Defensins”-
small peptides that are rich in cysteine. One family of these naturally-occurring anti-
infectives can inhibit bacteria, fungi, and viruses. Defensins bind to the membranes of
infecting organisms and increase permeability, decreasing the likelihood of resistance.
Lactoferrin is another naturally-occurring anti-infective. It is found throughout the
body in mucous membrane secretions, such as saliva, tears, nasal and bronchial
secretions, hepatic bile, and pancreatic fluids, and is essential for immune response.
Initial results from Brien Holden Vision Institute31 are promising and confirm that
selenium coated & furanone-coated lenses can prevent bacterial colonization. The
overall clinical performance of these lenses in terms of fitting, corneal & conjunctival
staining and subjective comfort were comparable to the commercially available lenses.
SUMMARY
Not surprisingly, researchers in the contact lens industry have shown significant
interest in agents that would provide antimicrobial properties for surfaces of contact
lenses because they could reduce or eliminate the adherence of microbes to contact
lenses and lens cases. Reducing exposure to infectious microorganism could make
contact lens wear possible for more patients and extended and continuous wear of
contact lenses could improve convenience and increase acceptance of contact lenses as
a vision care correction of choice. Patients could experience an added measure of
protection from microbial contamination without any extra effort on their part. An
additional benefit is that bacterial resistance to many antimicrobial agents is unlikely
because of their mechanisms of action.
Additional research is needed, and future needs include other aspects of antimicrobial
technology, such as whether antimicrobial lenses are compatible with lens care and
whether antimicrobial agents could cause an allergic response. It is also unknown
whether these agents would have unintended effects such as the build-up of
endotoxins. Another concern is the cost of manufacturing antimicrobial lenses. These
issues need to be adequately studied, and the answers will aid in the development of
contact lenses that incorporate antimicrobial or anti-infective technology.
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ANTI-MICROBIAL SURFACES AND MATERIALS FOR CONTACT LENSES & LENS CASES: THE
FUTURE & CHALLENGES MCQ’s
1. What is the percentage of soft contact lens users among the total contact lens
wearers?
a. 60%
b. 80%
c. 70%
d. >90%
2. What is the highest risk factor for microbial keratitis in developed countries?
a. Ocular trauma
b. Contact lens wear
c. Co-existing ocular diseases
d. Systemic diseases
3. Identify the possible cause/s of contact lens related ocular inflammation
a. Hypoxia
b. Presence of bacterial endotoxin
c. Cytotoxicity of care solutions
d. All of the above
4. Which one possibly can have the greater density of biofilm during asymptomatic
lens wear?
a. Contact lens surface
b. Surface of CL case
c. Solution bottle
d. All of the above
5. Identify the statement which is TRUE
a. In a biofilm, microorganisms will not be adhered to each other; but
adheres to the lens or CL surface.
b. The cells of a microorganism growing in a biofilm are physiologically
same as planktonic cells of the same organism
c. Biofilm will have an outer shell which protects the organisms inside
d. It takes at least 36-48hrs for the formation of biofilm on the new lens or
case surface
6. Silver retards the adherence and colonization of microorganisms through
a. Inhibition of DNA & RNA replication
b. Disruption of the cell membrane
c. Interference with cell respiration
d. All of the above
7. Polymeric quaternary ammonium compounds used in CL solution acts as
a. Disinfectant
b. Buffering agents
c. Viscosity enhancing agents
d. Cleaner
8. Polymeric Pyridinium Compounds
a. Prevents bacterial multiplication
b. Penetrates the bacterial cell wall and destroys
c. Oxidize bacterial cells and prohibits cell growth
d. None of the above
9. “Defensins” are
a. Quorum-Sensing blocker
b. Anti-infective agent
c. Free-radical producing aent
d. Polyquat
10. During asymptomatic contact lens wear, the type of organism isolated from the
lens surface are mostly
a. Gram ve bacteria
b. Gram +ve bacteria
c. Fungi
d. Protozoa
ResearchGate has not been able to resolve any citations for this publication.
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We cultured Soflens (polymacon) contact lenses to determine the number of microorganisms present following normal patient wear and handling just prior to disinfection. Total protein deposited was determined for the companion lens from each patient. A random population of 109 adapted soft contact lens patients participated in the study. Some patients participated more than once, resulting in a total of 196 lenses being cultured and 195 lenses analyzed for total protein. The left lens was cultured immediately. The right lens was extracted at 70 degrees C in sodium hydroxide, and the total protein in the extract determined using a modified Lowry protein assay. The mean protein deposition per lens was 3.4 micrograms (median 2 micrograms per lens; range less than 1 to 78 micrograms/lens). Microorganisms were cultured from 95% of the lenses. The mean bacterial count (in colony forming units per lens) was 2,482 (median: 123; range less than 3 to 150,000). Fungal contamination was found on 11% of the lenses at very low levels (3-9 yeast/lens and 3-18 mold/lens). Statistical analysis found no significant relationship between bacterial bioburden and any of the study parameters, including total protein, lens age, or subjective evaluation of lens cleanliness.
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Microbial keratitis is a potentially binding disease that is rare in normal eyes unless associated with contact lens (CL) wear. To assess the risks of CL use, and other major causes, for keratitis, a case-control study of 91 cases of keratitis including 60 CL users was done. Relative risks (RR) and population attributable risk percentages (PAR%) for keratitis were estimated for different causes and for the different types of CL. The RR (95% confidence intervals) for CL wear was 80 (38-166) and for trauma cases 14 (6-32) compared with cases of keratitis without a predisposing condition. The PAR% for microbial keratitis attributed to CL wear was 65%. The RR for overnight wear soft lenses was 21 (7-60), for daily-wear soft lenses 3.6 (1-14), and for polymethylmethacrylate hard lenses 1.3 (0-9) compared with gas-permeable hard lenses. Continuous periods of CL wear for more than 6 days was associated with increased risk. CL wear is now the commonest cause, and has the highest risk, for new cases of microbial keratitis at Moorfields Eye Hospital. Soft CLs, especially extended-wear lenses, carry a significantly higher risk than do hard lenses for this disease.