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Year XXIII, N. 8, May 2020
Innovation in Ophthalmology
Preoperative preparation of the eye with TiAB wipes
significantly reduces bacterial load: a case series
Franco Passani, Rosario Denaro, Flavio Dalle Lucche, Andrea Passani, Eva Maria Parisio,
Giulio Camarlinghi, Chiara Vettori
O
Year XXIII, N. 8, May 2020
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series Franco Passani, Rosario Denaro, Flavio Dalle Lucche, Andrea Passani, Eva Maria Parisio, Giulio Camarlinghi, Chiara Vettori
ISBN 978-88-6756-555-9ISSN 2035-0252
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Contents
Abstract 2
Introduction 2
Materials and methods 5
Results 6
Discussion 8
Conclusions 10
References 10
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series Franco Passani1, Rosario Denaro1, Flavio Dalle Lucche1, Andrea Passani2, Eva Maria Parisio3, Giulio Camarlinghi3, Chiara Vettori31 High-Complexity Ophthalmology Unit, Massa-Carrara, Italy2 Private Ophthalmologist, Pisa, Italy3 Unit of Chemical-Clinical and Microbiological Analysis, San Luca Hospital, Usl Toscana Nord Ovest,
Lucca, Italy
2
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series
Abstract
Objective: To evaluate the efficacy of a
commercially available non-antibiotic TiAB-
based cleansing wipe for the eyelids in re-
ducing bacterial load on the ocular surface
before cataract surgery.
Methods: A case series study was con-
ducted at the Ophthalmology Unit of Massa
Carrara to gather the first clinical experien-
ces with this product (TiABLO®). The pur-
pose of this study was to evaluate the effect
of TiAB eyelid disinfection on periocular and
eyelid microorganisms in 20 patients waiting
for cataract surgery who were found positive
for eyelid microorganisms, out of 70 consec-
utive patients analysed. The patients received
a preoperative treatment with a wipe soaked
in a solution containing xanthan gum and
titanium dioxide coated silver (TiABLO®,
NTC). The periocular bacterial count was
determined up to 2 hours after treatment.
Results: In 16 out of 20 patients (80.0%)
there was total eradication of the resident
bacterial population. Measurements at T30’,
T60’, and T120’ in the responders showed
a percentage reduction of 50%, 60%, and
100%, respectively, of the microbial load on
the eyelids.
Conclusions: The results suggest that the
use of TiAB-based eyelid wipes as a com-
plementary prophylactic method is able to
reduce the periocular bioburden before any
ocular surgery.
Introduction
Postoperative endophthalmitis is a serious
complication of intraocular surgery. Sev-
eral different bacterial species are able to
cause endophthalmitis after surgical proce-
dures[1,2], and sometimes with serious con-
sequences and poor final visual outcomes[3].
Endophthalmitis can occur following any
ocular surgery; however, because of the
sheer number of operations, 90% of cases
are associated with cataract surgery[4]. The
principle of reducing bacterial colony counts
in the surgical field is widely practised in
surgery. As for cataract surgery, a number of
prophylactic protocols have been designed,
their rationale being mainly based on the
experimental reduction in conjunctival
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series
3
commensals by topical application of antibi-
otics, disinfectants or both[5].
Etiologic agents of acute postoperative endophthalmitisThe etiologic agents of acute postoperative
endophthalmitis are generally microorgan-
isms of the eyelid margin, conjunctiva, and
tear film. The normal microbiota from the
eyelid and conjunctiva has already been
described[6]. Depending on the study, the
frequency of isolation of bacteria ranges
from 16% to 100%, with microbial growth
shown in approximately 50% of swabs from
the conjunctiva and tears, and in more than
50% of swabs from the eyelids[6]. The most
common bacteria isolated from the eyelids,
conjunctiva, and tears are Gram-positive
bacteria, mostly coagulase-negative Staphy-
lococcus spp. Bacteria present on the eyelid
are responsible for acute postoperative en-
dophthalmitis[7].
To prevent the onset of postoperative en-
dophthalmitis, several prophylactic strat-
egies have been used. These approaches,
which often feature the use of topical anti-
biotics, are focused on reducing the bacterial
load on the ocular surface on the assumption
that this could reduce the risk of endoph-
thalmitis[8]. The most commonly used treat-
ments are perioperative topical antibiotics,
preoperative topical antibiotics, intracameral
antibiotics, antibiotics at the end of the sur-
gery, and postoperative topical antibiotics[9].
Bacterial resistance to antibioticsIt is important to underline that among
the factors responsible for the onset of en-
dophthalmitis is the increased resistance of
Staphylococcus and other pathogenic bacteria
to an increasing number of antibiotics, in-
cluding the latest generation (fluoroquino-
lones). The most disturbing and widely ex-
panding phenomenon throughout the world
is the accumulation of multiple forms of re-
sistance in some pathogenic bacteria. These
multiresistant bacteria manage to prolifer-
ate normally even in the presence of mul-
tiple classes of antibiotics. Methicillin-resis-
tant Staphylococcus aureus (MRSA) strains
are the leading cause of hospital infections
in the United States, and are increasing-
ly causing infectious conjunctivitis, kerati-
tis, endophthalmitis, and orbital cellulitis.
Methicillin-resistant Staphylococcus species
are not only resistant to methicillin, but
also to all β-lactam antibiotics. Additionally,
methicillin resistance might also be related
to resistance to other classes of antibiotics,
which may limit treatment options. Methi-
cillin-resistant Staphylococcus is a major con-
cern for global public health. Recently, stud-
ies have focused on endophthalmitis caused
by methicillin-resistant Staphylococcus[10].
Some notable features of methicillin-resis-
tant Staphylococcus-associated endophthal-
mitis are as follows: a rise in the reported
incidence rate[11], an association with poor
visual outcome, and an association with re-
sistance to fluoroquinolones[12].
The development of bacterial resistance to
specific antibiotics is a factor that ophthal-
mologists must never overlook. The wide-
spread and sometimes inappropriate use
and incorrect dosages of broad-spectrum
antibiotics, often aggravated by incomplete
compliance and/or inadequate duration of
treatment, generate the development of
4
resistance. The antibiotic resistance data
emerging from recent studies highlight the
need for ophthalmologists to develop prac-
tical and prudent strategies in the adminis-
tration of topical antimicrobial therapies[13].
The continuing appearance of antibiotic re-
sistance in pathogenic and opportunistic mi-
croorganisms obliges the scientific commu-
nity to constantly develop new disinfectants
and drugs. Few new antibiotics have been
introduced by the pharmaceutical industry in
the last decade, and none of them have im-
proved the activity against multidrug-resis-
tant bacteria. To date, the only prophylactic
measure that has been shown consistently
to reduce the risk of endophthalmitis after
invasive ocular procedures, such as cataract
surgery and intravitreal injections, is the pre-
procedural application of povidone iodine
(PVI) to the ocular surface[14]. However, the
exact concentration of PVI to use remains
controversial, with most retinal physicians
using a concentration between 1.25% and
10%. The guidelines of the European Society
of Cataract and Refractive Surgeons (ESCRS)
state that a mandatory step to reduce bacte-
ria in the wound area is to apply PVI 5-10%
to the cornea, conjunctival sac and periocu-
lar skin for a minimum of 3 minutes prior to
surgery. Where PVI is contraindicated (true
allergy is rare and hyperthyroidism only a
relative contraindication to this single use),
aqueous chlorhexidine 0.05% may be used[15].
Although PVI has been recognized as a safe,
effective broad-spectrum, biocidal agent for
many years, there are a few studies demon-
strating the abrasiveness of iodine treatment
leading to corneal epithelial and endothelial
cell damage after treatment with PVI with
concentrations higher than 1–5% and treat-
ment longer than 2 minutes[16,17].
It is necessary also to highlight the mech-
anism of cross-resistance between antibio-
tics and antiseptics, such as chlorhexidine,
whose use would increase, according to
some researchers, the antibiotic resistance
of some pathogenic bacteria.
While chlorhexidine has been successfully
used as part of a multifaceted intervention
to reduce the prevalence of carbapenem-re-
sistant Klebsiella pneumoniae in hospitals, the
observation that exposure to chlorhexidine
leads to colistin resistance means that erad-
ication of potentially colistin- and carbap-
enem-resistant isolates is very problematic.
Since the isolates have also acquired in-
creased resistance to chlorhexidine, this also
makes the prevention of colonization with
the isolates more difficult, with a potential
to either prolong existing outbreaks or lead
to new outbreaks[18].
Novel disinfection method with TiAB ocular wipesIt has been repeatedly stressed that prepara-
tion of the ocular surface is essential to re-
duce the onset of postoperative endophthal-
mitis: a mandatory measure is to reduce the
bioburden on the cornea, conjunctival sac,
and periocular skin. The use of new non-an-
tibiotic molecules with proven antipatho-
genic activity can ideally complement the
mandatory disinfection of the ocular surface
of the conjunctival sac level with PVI 5% for
preoperative asepsis by reducing bioburden
at the palpebral and eyelash level[15].
In this study we used, as a novel disinfection
method, ocular wipes soaked in a solution
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series
5
containing TiAB. The TiAB complex is a sil-
ver preparation in which the silver ions are
bound to microcrystals of titanium dioxide
(TiO2) by means of covalent bonds, so that
the silver remains stable in the ionic (active)
status even in the presence of light. The use
of silver to control infections was common
in ancient civilizations[19]. The discovery of
antibiotics in the early 20th century led to a
cessation in the development of silver as an
antimicrobial agent. However, the develop-
ment of increasing levels of bacterial resis-
tance to most antibiotics in recent years has
led to re-examination of the potential of this
ancient remedy[20] including studies with pa-
tients using colloidal silver and antibiotics[21].
Although technological advances have
enabled the development of silver (Ag)
nanoparticles characterized by a favourable
surface-to-volume ratio and higher activi-
ty than that of traditional silver-based an-
tiseptics, these nanoparticles have a high
tendency to aggregate, causing silver to lose
its physicochemical properties and therefore
its biological activity. The way to avoid this
problem and preserve the high efficacy of
silver preparations is to immobilize the Ag
microparticles on inorganic carriers, such as
titanium dioxide (TiO2).
The main property of the TiAB microparti-
cles is that the titanium dioxide binds high
amounts of silver ion, in a stable form, in
concentrations higher than those common-
ly recorded in currently common drugs and
devices, thus avoiding delivery of highly
toxic concentrations of non-ionic silver.
The microparticles, due to the fact that Ag+
ions are linked to titanium dioxide by indis-
soluble covalent bonds, avoid the effect of
tissue and cellular accumulation that is ob-
served for many common products (hinder-
ing and delaying the process of deposition of
granulation tissue at the basis of the healing
process). Thus, TiAB is a powerful and stable
bacteriostatic agent able to reduce the bacte-
rial/mycotic/viral growth where applied.
Cassino et al.[22] evaluated the efficacy of
the TiAB complex administered as a spray
on colonized and/or infected chronic skin
lesions that were not cleansed, to assess its
antibacterial barrier activity in promoting
wound healing. TiAB treatment was effec-
tive in the removal of the signs of coloniza-
tion and/or infection in 100% of cases, with
a 76% mean reduction in the ulcerated area.
This study tested the efficacy of eyelid dis-
infection using commercially available
cleansing wipes based on TiAB to reduce
the ocular surface bacterial load in patients
before ocular surgery.
Materials and methods
This case series included 70 adults (age 64–
88, average 77) of either sex (40 women and
30 men), who were scheduled for ocular sur-
gery with implantation of intraocular lenses
(IOLs). The final investigation was carried
out on the 20 patients who were found to be
bacteria-positive at the first swab. The find-
ing that 50 patients were negative at the first
swab can be explained by the fact that pa-
tients, in anticipation of the upcoming oper-
6
ation, paid greater attention to cleaning the
periocular area, especially on the morning
of the operation.
Prior to surgery each patient underwent the
following study protocol: a pre-disinfection
swab was taken on the whole palpebral
surface (superior and inferior) and on the
eyelashes with the eye closed. The eyelids
and surrounding skin were then careful-
ly cleansed by wiping with an ocular wipe
soaked in a solution containing xanthan
gum and TiAB (TiABLO®, NTC). TiABLO®
is marketed in packs containing individual-
ly wrapped, single-use wipes.
At 30’, 60’, and 120’ after TiABLO® disin-
fection, eyelids swabs were taken using the
same procedure (Figure 1).
All the collected samples were sent to the
microbiology laboratory of San Luca Hospi-
tal in Lucca, Italy. The swabs were cultured
on specific agar plates (blood agar, chocolate
agar, MacConkey agar, Columbia CNA agar,
Sabouraud’s dextrose agar and Schaedler
agar). Bacterial growth on each plate was
determined after aerobic, anaerobic and
CO2 incubation at 37 °C. Negative cultures
of swabs were reported after 48 hours’ incu-
bation. For positive cultures, a semiquantita-
tive analysis was performed, and the results
were reported as ‘trace’, ‘few’, ‘moderate’
and ‘abundant’ growth for each of the bac-
terial isolates. Identification of the colonies
was carried out by MALDI-ToF (Vitek MS;
bioMérieux, Marcy l’Étoile, France).
Results
The bacterial species isolated in the differ-
ent swabs on the eyelids and their relative
concentrations are shown in Table 1.
The eyelid showed the presence of S. epider-
midis plus other coagulase-negative staph-
ylococci (CoNS) and Bacillus cereus (68.8%
and 25.0%, respectively) as the most fre-
quent microorganisms.
There was a significant reduction (80.0%)
in the number of patients with positive bac-
Figure 1. Diagram of the experimental protocol.
TiABLO®treatment
Swab after60 minutes Surgery
First swab Swab after30 minutes
Swab after120 minutes
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series
7
terial samples after TiABLO® treatment.
Of the 20 patients positive at baseline, 16
showed total bacterial eradication 2 hours
after treatment with TiAB wipe (Figure 2).
A numerical value was given to the abun-
dance of bacterial growth found on the eye-
TABLE 1. Bacterial species isolated on the eyelids of the 16 responder patients and their concentrations at each timepoint (absent = negative, trace = 1, few = 2, moderate = 3, abundant = 4).
Patient Baseline 30’ 60’ 120’
1*Staphylococcus epidermidis
and other staphylococci CoNS 1 Citrobacter freundii 2 Corynebacterium macginleyi 3 Negative
2Bacillus cereus/thuringiensis/
mycoides 2 Negative Negative Negative
3Bacillus cereus/thuringiensis/
mycoides 2 NegativeStaphylococcus epidermidis
and other staphylococci CoNS 1 Negative
4Bacillus cereus/thuringiensis/
mycoides 1Staphylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative
5 Enterobacter cloacae 4 Enterobacter cloacae 2 Negative Negative
6Stahpylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative
7Bacillus cereus/thuringiensis/
mycoides 1 Negative Negative Negative
8Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative Negative
9Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative Negative
10*Staphylococcus epidermidis
and other staphylococci CoNS 1 Enterobacter aerogenes 2 Negative Negative
11Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative Negative
12Staphylococcus epidermidis
and other staphylococci CoNS 2Staphylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative
13Staphylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative
14Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative Negative
15Staphylococcus epidermidis
and other staphylococci CoNS 3Staphylococcus epidermidis
and other staphylococci CoNS 2Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative
16Staphylococcus epidermidis
and other staphylococci CoNS 1Staphylococcus epidermidis
and other staphylococci CoNS 1 Negative Negative
CoNS, coagulase-negative staphylococci.* Patients 1 and 10 went to the toilet during the observation period.
8
lid of individual patients: absent = 0, trace =
1, few = 2, moderate = 3, abundant = 4.
Table 1 and Figure 3 summarize the re-
sults for each of the 16 responder patients.
In the four non-responder patients, the
presence of Staphylococcus epidermidis and
CoNS was maintained throughout the ob-
servation period.
In the 16 responder patients, measurements
at T30’ and T60’ showed negativization of
44% and 63%, respectively, of the microbi-
al load on the eyelashes of the treated eyes
and complete bacterial eradication after 2
hours (Figure 3).
Discussion
In addition to the classical procedures such
as cataract surgery, the number of intraocu-
lar operations is increasing as new therapies
are developed. Endophthalmitis caused by
microorganisms present on the ocular sur-
face may occur as a consequence of these
Figure 2. Positive patients at baseline and at 120’ after treatment with TiAB wipes.
Figure 3. Bacterial burden at each timepoint in the 16 responder patients (negative = 0, trace = 1, few = 2, moderate = 3, abundant = 4).
Posi
tive
patie
nts (
N.)
0Baseline 120’
20
4
10
15
25
5
20
0
Bact
eria
l bur
den
1 2Patient number
1.5
T0
2.5
4.5
0.5
3.5
2
3
1
4
3 4 5 6 7 8 9 10 11 12 13 14 15 16
T30’ T60’ T120’
Preoperative preparation of the eye with TiAB wipes significantly reduces bacterial load: a case series
9
treatments and is a permanent concern
for every eye surgeon. For this reason, the
search for optimal preoperative procedures
to help reduce its incidence is a constant
challenge.
The source of pathogens for endophthal-
mitis is mainly the ocular and palpebral
surface and the eyelashes of the patients. It
was demonstrated that organisms isolated
from the vitreous in endophthalmitis were
genetically indistinguishable from those
derived from the eyelids, conjunctiva and
nose in 82% of cases[23]. The results showed
an important microbial load from the eye-
lashes, which highlights the need to main-
tain preoperative asepsis of eyelashes as a
complementary measure to the disinfection
of the ocular surface and conjunctiva. Our
findings are consistent with those of previ-
ous authors who found that CoNS species
(of which Staphylococcus epidermidis is the
most common) are identified in up to 70%
of cases with positive vitreous cultures[24].
Topical prophylactic antibiotics have long
been used in ocular surgery, and this prac-
tice has also been transferred to intravitreal
injections. Antibiotic treatments, particular-
ly newer-generation fluoroquinolones, can
provide broad-spectrum antimicrobial cov-
erage with substantial ocular penetration,
and it was hoped that prophylactic antibiot-
ics could reduce the risk of postocular sur-
gery endophthalmitis.
Antibiotics in eye infectionsIncreasing use of antibiotics for treatment
and prophylaxis of eye infections has result-
ed in the emergence of resistant ocular or-
ganisms. This is especially true for intravit-
real procedures where discontinuous use of
the antibiotic favors the onset of resistance
and increases the incidence of endophthal-
mitis[25]. The use of topical antibiotics for
prophylaxis of postoperative endophthalmi-
tis has paralleled the recent increase in the
number of patients undergoing intraocular
procedures. This has resulted in the upsurge
of antibiotic-resistant organisms colonizing
the ocular microbiota and causing postop-
erative infections. Contemporary ocular
staphylococci isolates, the leading causes of
bacterial endophthalmitis, are becoming in-
creasingly resistant to the most commonly
used topical antibiotic agents.
Topical antiseptics in eye infectionsTopical antiseptics, such as silver, differ
from antibiotics: they have multiple sites
of antimicrobial action on target cells
and therefore a low risk of bacterial resis-
tance[26]. As a result, antiseptics have the
potential to play an important part in con-
trolling bioburden in periocular skin and
eyelids, while limiting exposure to antibi-
otics and reducing the risk of promoting
further antibiotic resistance. Along these
lines, it has recently been scientifically doc-
umented that complex particles carrying
silver can be a valid tool in antimicrobial
treatments (antibacterial-antifungal-an-
tiviral) in many surface, skin and mucous
diseases[27].
To date, there are three known mechanisms
by which silver acts on microbes. Firstly,
silver cations can form pores and puncture
the bacterial cell wall by reacting with the
peptidoglycan component[28]. Secondly, sil-
10
ver ions can enter the bacterial cell, both in-
hibiting cellular respiration and disrupting
metabolic pathways resulting in generation
of reactive oxygen species[29]. Lastly, once in
the cell, silver can also disrupt DNA and its
replication cycle[30].
The only adverse health effect reported by
silver is argyria, an irreversible pigmenta-
tion of the skin that is mostly an esthetic
concern[31].
A wipe for ocular hygiene formulated with
TiAB has recently been developed. The
TiAB complex is a formulation based on a
silver preparation, in which the silver ions
are bound to microcrystals of titanium diox-
ide (TiO2) by means of covalent bonds and
therefore remain stable in the ionic (active)
state even in the presence of light.
TiABLO® Ophthalmic Wipe forms a humid
barrier protecting the whole periocular re-
gion and helps in fighting bacterial and vi-
ral infections. This distinctive feature makes
TiABLO® suitable for before and after ocu-
lar surgery as it promotes maintenance of
a physiological condition in the periocular
region.
Disinfection with TiABLO® was able to
eliminate the microbial load in 80% of pos-
itive patients, not only the one affected by
CoNS species, but also all of those affected
by B. cereus. It must be noted that B. cereus
is a major cause of severe keratitis, endoph-
thalmitis, and panophthalmitis; alarming
ocular infections due to B. cereus appear to
have increased over the last 15 years. B. ce-
reus produces β-lactamases, which makes it
resistant to β-lactam antimicrobial agents,
including the third-generation cephalo-
sporins[32], and quite difficult to completely
eradicate.
Conclusion
Preoperative eye preparation using TiAB
ocular wipes seems to be an efficient strat-
egy to complement disinfection of bacteria
of the eyelashes and periocular surface and
help prevent intraocular infections. The rate
of positive cultures from palpebral and eye-
lash samples decreased significantly and
in a very short period considering the total
bacterial load and culture-positive eyes, af-
ter the topical use of TiABLO® wipes. Fur-
ther studies with larger populations are
needed to confirm these preliminary results.
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