Franco Passani, Rosario Denaro, Flavio Dalle Lucche ... · 5/8/2020 · isms of the eyelid margin, conjunctiva, and tear film. The normal microbiota from the eyelid and conjunctiva

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

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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


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


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


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


mycoides 2 NegativeStaphylococcus epidermidis

and other staphylococci CoNS 1 Negative


mycoides 1Staphylococcus epidermidis

and other staphylococci CoNS 1Staphylococcus epidermidis


5 Enterobacter cloacae 4 Enterobacter cloacae 2 Negative Negative

6Stahpylococcus epidermidis





mycoides 1 Negative Negative Negative

8Staphylococcus epidermidis

and other staphylococci CoNS 1 Negative Negative Negative



10*Staphylococcus epidermidis

and other staphylococci CoNS 1 Enterobacter aerogenes 2 Negative Negative









and other staphylococci CoNS 1 Negative Negative









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’


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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