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Contact Lens & Anterior Eye 35 (2012) 53– 64

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Contact Lens & Anterior Eye

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Review

Protein deposition on contact lenses: The past, the present, and the future

Doerte Luensmann ∗, Lyndon JonesCentre for Contact Lens Research, School of Optometry, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada

a r t i c l e i n f o

Keywords:Protein depositionContact lensHydrogelPolyHEMASilicone hydrogelBiocompatibility

a b s t r a c t

Proteins are a key component in body fluids and adhere to most biomaterials within seconds of theirexposure. The tear film consists of more than 400 different proteins, ranging in size from 10 to 2360 kDa,with a net charge of pH 1–11. Protein deposition rates on poly-2-hydroxyethyl methacrylate (pHEMA)and silicone hydrogel soft contact lenses have been determined using a number of ex vivo and in vitroexperiments. Ionic, high water pHEMA-based lenses attract the highest amount of tear film protein(1300 �g/lens), due to an electrostatic attraction between the material and positively charged lysozyme.All other types of pHEMA-based lenses deposit typically less than 100 �g/lens. Silicone hydrogel lensesattract less protein than pHEMA-based materials, with <10 �g/lens for non-ionic and up to 34 �g/lensfor ionic materials. Despite the low protein rates on silicone hydrogel lenses, the percentage of dena-tured protein is typically higher than that seen on pHEMA-based lenses. Newer approaches incorporatingphosphorylcholine, polyethers or hyaluronic acid into potential contact lens materials result in reducedprotein deposition rates compared to current lens materials.

© 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

1. Introduction

Contact lenses represent a biomaterial that is widely used andrelatively easy to study, due to its ease of removal from the ocularsurface. Immediately after being placed on the eye, contact lensesare coated with a protein layer and most proteins attach stronglyto the material, with typically less than 50% being removed by con-ventional care regimens [1–3]. The deposition of certain proteinsto contact lenses has shown to increase the risk of microbial cellattachment to the lens material [4–6], and is also associated withinflammatory complications such as giant papillary conjunctivitis[7].

2. Proteins in the tear film

Protein deposition on contact lenses is substantially impactedby the lens material, and also by the protein concentration, proteinstructure and charge of the proteins within the tear film. Proteinsare a major component of the human tear film and perform a vari-ety of important tasks, which include protecting the ocular surfacefrom microorganisms, cell membrane transport/metabolism,regulating immune responses, protein folding, antioxidation, andact as protease inhibitors [8]. de Souza [9] identified 491 different

∗ Corresponding author at: Centre for Contact Lens Research, University of Water-loo, 200 University Ave West, Waterloo, N2l 3G1, ON, Canada.Tel.: +1 519 888 4567x37312; fax: +1 519 884 8769.

E-mail address: dluensma@uwaterloo.ca (D. Luensmann).

proteins and mucins in the tear film, ranging in size from 10 kDato 2360 kDa [9]. Approximately 80% of the proteins have a size of<100 kDa [9] and they range in charge from isoelectric points (pI) ofpH 1 to 11 [10]. Examples of proteins that have received the mostattention in contact lens research include lysozyme (14.3 kDa, pIpH 11.4), lactoferrin (80 kDa, pI pH 8.7) and albumin (66 kDa, pI pH5.2). The average pH of the tear film is 7.4, which results in lysozymeand lactoferrin being positively charged and albumin being nega-tively charged. Most proteins have a pI significantly above or belowpH 7.4, which helps their solubility in the tear film, as proteins areleast soluble if the environment is close to the protein’s pI, whichwould lead to increased aggregation and deposition rates [11,12].

The total protein concentration in the tear film ranges between6.5 and 9.0 mg/mL and varies between individuals [13]. A varietyof factors are known to influence the protein concentration in thetear film, including: time of the day [14,15], contact lens wear [16],age [17] and eye diseases such as Sjögrens syndrome [18]. Signif-icant differences in concentration are also seen when tearing isstimulated, compared to that seen with unstimulated tears [19].

3. The principals of protein sorption

Proteins adsorb to most surfaces, and while hydrophobic (non-polar) amino acids are typically protected inside the proteinmolecule, the hydrophilic (polar) amino acids, with and withoutcharged side chains, interact freely with their environment [20].If the charged side chains come into contact with an oppositelycharged surface, the adsorption process is further reinforced. Eachprotein is typically folded in a three-dimensional structure, which

1367-0484/$ – see front matter © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.clae.2011.12.005

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54 D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64

is held together by hydrophobic forces, hydrogen bonds and vander Waals forces [21]. However, the structure of most proteins ismetastable and the exposure to water-based solutions is energet-ically unfavorable due to an increase in Gibbs energy [22]. Whennow exposed to a solid surface – particularly hydrophobic surfaces– proteins tend to rearrange their structure and favor adsorptionto the surface in order to once again lower the Gibbs energy [23].Once proteins are unfolded and have coiled in a random manner,they are unable to perform their natural tasks, but instead mayinteract with other proteins/cells in an undesired manner. Theseunfolded, or “denatured” proteins, may cause aggregation or cantrigger immune reactions [24,25].

4. Analyzing protein deposits on contact lenses

A number of qualitative and quantitative techniques have beenapplied to analyze protein deposition on contact lens materials[26]. These can be broadly categorized into clinical assessment,biochemical and imaging techniques, each of which provides veryspecific information about the deposition on the lens material. Abrief overview is outlined in this section, describing some com-monly used techniques.

Subjective clinical grading provides a fast, non-destructivemethod of assessing visible deposition on contact lenses. Rudkoand Proby [27] described the degree of visible deposition on softcontact lenses using a slit lamp, by categorizing the deposits basedupon the level of magnification required to visualize the deposits,on a dry or wet lens. Despite some modifications of this classifi-cation system over the years, research has shown that there is alack of correlation between these so-called “Rudko scores” and thetotal amount of protein deposited on lenses, as determined usingquantitative techniques [28]. Further, it is difficult to differenti-ate between types of deposition (for example whether the visibledeposits are protein or other tear film components) [28,29] usingsubjective clinical grading.

Biochemical laboratory-based techniques provide detailed infor-mation on the quantity and/or type of deposition present. Proteinassays typically require extraction of the proteins from the contactlens before they can be analyzed, and focus on the identificationand/or quantification of the protein content. Chemical reagents thatare typically used to undertake the extraction include urea, guani-dine hydrochloride, potassium thiocyanate, potassium perchlorate,hydroxylamine, ethylene dithretyl acetamide, sodium dodecyl sul-fate (SDS), dithiothreitol (DTT), and acetonitrile/trifluoroacetic acid(ACN/TFA) [30,31]. The efficiency of these reagents with respectto removing the protein depends on the type of protein and com-position of the lens material, and may remove as little as 25% ofthe deposited substance [32,33]. Once extracted, general proteinassays such as the bicinchoninic acid (BCA) assay can quantifythe total amount of protein [34–36], while amino acid analysis[32] or sodium dodecyl sulfate polyacrylamide gel electrophore-sis (SDS-PAGE) have been used to quantify and identify depositedproteins. Another sensitive technique for identifying different typesof proteins is high performance liquid chromatography (HPLC),which provides semi-quantitative results [31,37]. The conforma-tional state of deposited lysozyme has further been determinedusing the micrococcal activity assay [38–40].

Imaging techniques provide primarily qualitative results, withsome techniques providing quantitative information [41,42]. Anumber of microscopy techniques, such as light and dark fieldmicroscopy, phase contrast and interference microscopy havebeen used to examine gross and fine morphological aspects ofdeposition [41,43]. For higher resolution imaging and elemen-tal analysis, scanning electron (SEM) and transmission electronmicroscopy (TEM) have successfully been adopted [44–46]. Atomic

force microscopy (AFM) provides details at the nanometer rangeand is therefore even more advanced compared to conventionalscanning microscopy techniques [47]. In contact lens research, AFMhas been used to image the interaction between surface rough-ness and tear film deposition [5,48–50]. Confocal laser scanningmicroscopy (CLSM) is a unique technique that allows the examinerto scan directly into the contact lens matrix, making it possible todetermine the penetration depth of proteins. [51,52]. In contrastto microscopy, spectroscopic techniques typically measure theenergy that is either absorbed or emitted by the deposited speciesand can, for example, identify proteins, carbohydrates or lipids byanalyzing specific absorption bands. Ultraviolet (UV) and fluores-cence spectroscopy [42], attenuated total reflectance (ATR) [53],electron spectroscopy for chemical analysis (ESCA) [54], surfacematrix assisted laser desorption/ionisation (MALDI) mass spec-trometry [55,56] and radiolabeling [57,58] are just some examplesof spectroscopic techniques used to analyze protein deposition.The conformational state of deposited proteins has further beeninvestigated using electron spin resonance (ESR) spectroscopy [59]or Fourier transform infrared-attenuated total reflectance spec-troscopy (FTIR-ATR) [53].

A number of factors need to be considered when evaluating thelevel of protein deposition on contact lenses. These include thelength of time the lenses were worn for, the use of specific con-tact lens care regimens, the extraction and quantification methodemployed, inter-subject differences and finally an acceptance thatin vitro experiments may not necessarily mimic ex vivo situations.

This review provides an overview of quantitative protein sorp-tion to soft contact lens materials that have been used in the past,materials presently in use and materials that could potentially beused in the future. Most information is currently available on thetear film proteins lysozyme, lactoferrin and albumin, therefore spe-cific information on these proteins are included in this review,where available.

5. Hydrogel contact lenses – the past

Poly-2-hydroxyethyl methacrylate (pHEMA) was invented byOtto Wichterle more than 50 years ago and has shown such accept-able biocompatibility that even today it is still used in manybiomedical fields, for blood-contacting implants, artificial organs,drug delivery devices, intraocular lenses (IOL) and contact lenses[60–62]. Hydrated pHEMA has a water content of 38%, but variousmonomers or polymers are frequently incorporated for use in con-tact lens materials, to enhance material strength and to increaseequilibrium of water content and hence oxygen permeability [63].Currently, more than 150 different types of soft contact lenses areavailable, most of which are still based on pHEMA compositions[64].

5.1. 2-Hydroxyethyl methacrylate

Contact lens materials that primarily consist of pHEMA are cat-egorized by the Food and Drug Administration (FDA) as Group I(non ionic, <50% water) materials and account today for approx-imately 10% of all newly fitted soft contact lenses worldwide[65]. The literature to-date unanimously agrees that contact lensesmade of pHEMA deposit less protein than pHEMA materials com-bined with other monomers, particularly methacrylic acid orN-vinylpyrrolidone [31,66].

Despite the low deposition level of this material, proteins can bedetected after as little as 1 min of lens wear [67,68]. Highly abun-dant proteins in the tear film (e.g. lysozyme; lactoferrin) depositonto pHEMA lenses at quantities that are similar or even lowerthan less abundant proteins such as albumin or Immunoglobulin

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D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64 55

G [58,66]. The amount of protein deposition is further impactedby lens manufacturing technique as suggested in a previous study.These data showed that lysozyme and albumin levels on EGDMA-crosslinked pHEMA materials are 1.5–2× higher on lenses that weremanufactured using a lathe-cut technique as compared to thosethat were spun cast [69,70].

The total amount of protein depositing on worn pHEMA lensesranges between 4 and 75 �g/lens [28,30,32,34,71], while in vitroexperiments have detected 16–23 �g of lysozyme [72] and 4.5 �g[73] to 41 �g [4] of albumin per lens. The overall protein sur-face coating on pHEMA lenses worn for 2 h is approximately10–30 ng/cm2, as determined by X-ray photoelectron spectroscopy(XPS) [56].

5.2. Methacrylic acid

Methacrylic acid (MAA) is the most commonly employedhydrophilic monomer that is used in combination with pHEMAmaterials. It is found in some FDA Group III materials (ionic,<50% water) and is almost always present in FDA Group IV (ionic,>50% water) lens materials [63]. Copolymerization with this highlynegatively charged (anionic) monomer increases the water con-tent of pHEMA, which results in higher oxygen permeability.However, the negatively charged carboxyl groups of MAA attractpositively charged proteins such as lysozyme, and both ex vivoand in vitro studies have shown that with increasing amountsof MAA the amount of lysozyme accumulation increases [58,74],while negatively charged proteins such as albumin decrease[58].

Although several contact lens materials are categorized withinFDA Group IV, the amount of MAA varies greatly. The impactof this is shown by the fact that materials containing “low”amounts of MAA such as vifilcon A [58] (which also includevinyl pyrrolidone), typically deposit less than half the amountof total protein compared to etafilcon A [32,74], which containsmore MAA. Ex vivo results have determined 82–488 �g totalprotein on vifilcon A lenses, which is similar to in vitro experi-ments investigating lysozyme alone [72]. The amount of lysozymedepositing on worn etafilcon A (Group IV) lenses accounts for85% [75] to 92% [31] of the total protein. The average amount ofdeposited lysozyme is approximately 1300 �g/lens, ranging from209 to 3700 �g/lens [28,34,37,38,71,76,77] as determined by var-ious extraction/quantification methods. Slightly lower amounts oftotal protein are typically found when using spectroscopy methods[75,78]. In vitro studies are in reasonable agreement with ex vivoresults, reporting on 428–2200 �g of lysozyme [31,35,39,72,73],6–11 �g of lactoferrin [79] and <1–4 �g of albumin [3,73] per lens.

In vitro CLSM experiments have determined that etafilcon Adeposits both lysozyme and albumin throughout the lens material,when exposed for >24 h [3,52]. However, vifilcon A lenses accumu-late lysozyme at slightly higher concentrations in the outer surfaceregion, but significant amounts are still detected within the lensmatrix [80]. After 2 h of lens wear, the protein surface coating onetafilcon A lenses is approximately 70–220 ng/cm2, as determinedby XPS analysis [56].

Comparisons between pHEMA-MAA and crosslinked pHEMAlenses have determined that albumin deposited on pHEMA exhibitsconformational changes earlier than pHEMA-MAA lenses [69]. ESRspectroscopy has further shown that albumin binds irreversiblyand denatures within 1 h of exposure to vifilcon A, which is fasterthan that measured on etafilcon A [59]. These findings suggest thatthe amount of MAA in the material impacts the stability of thedeposited protein. Finally, the amount of active lysozyme on etafil-con A lenses is typically >75%, as determined by the micrococcalactivity assay [39,76].

5.3. N-vinylpyrrolidone

N-vinylpyrrolidone (NVP) is another hydrophilic monomer thatis used to increase the water content of either pHEMA or poly-methyl methacrylate (pMMA) [63]. NVP or PVP, which is thepolymer of NVP [11], can either be incorporated into the bulk mate-rial or is grafted onto the material’s surface. NVP is present in mostFDA Group II lenses (non ionic, >50% water), but is also seen in com-bination with MAA in certain FDA Group IV materials (e.g. vifilconA). PVP is a component that is often incorporated in biomaterialsto increase surface hydrophilicity and to reduce protein deposition[81].

The incorporation of NVP into pHEMA materials impacts theoverall charge of the material, to a small but noticeable degree:with an increasing NVP content, less positively charged lysozymeand more negatively charged albumin deposits on HEMA-basedlenses [58,66]. A study using synthesized hydrogels containing 80%HEMA, 1% MAA and 19% NVP found similar amounts of albumin andlysozyme on these lenses, but surprisingly more than twice as muchof the larger protein lactoferrin, after incubation in an artificial tearsolution (ATS) containing various proteins [82].

The total amount of protein detected on patient-worn lensesranges from 7 to 87 �g/lens [28,32,42,75,78,83], with most stud-ies reporting 30–40 �g/lens [28,42,78,83]. In vitro studies thatdetermined the amount of individual proteins on NVP-containinghydrogels have reported on 35–68 �g/lens for lysozyme [39,72],4–7 �g/lens for lactoferrin [79] and approximately 2–7 �g/lens foralbumin [73,84].

Similar to other pHEMA-based materials, lysozyme can bedetected throughout the NVP-containing lens material alphafilconA after only 1 day of exposure to a single protein solution, as deter-mined by CLSM using fluorescently conjugated lysozyme [80].

Clearly, MAA and NVP have a strong impact on protein sorptionto pHEMA-based materials. However, other principal componentsnot reviewed in this paper may also play important roles in mod-ifying or controlling protein deposition. Some examples includemethyl methacrylate and other di- or trifunctional methacry-lates (which are mainly hydrophobic), allyl methacrylate, divinylbenzene diacetone acrylamide, isobutyl methacrylate, vinylacetate, hydrophilic 2,3-dihydroxypropyl methacrylate, diacetoneacrylamide (which is ionic), phosphorylcholine, the crosslinkerEGDMA, polyvinyl alcohol (which is nonionic) and others [63].

In summary, hydrogel lenses are made of a number of differ-ent hydrophobic or hydrophilic, negatively or positively chargedmonomers, which have a significant impact on the amount ofprotein deposition. Group I (non-ionic; <50% water) lenses typ-ically deposit the lowest amount of protein, followed by similaramounts on Group II (non-ionic; >50% water) and Group III (ionic;<50% water), with the most being found on Group IV (ionic; >50%water) lenses, which deposit approximately 10 times more pro-tein than Group I lenses (Table 1a). The amount of protein foundon worn Group I, II and III lenses is typically less than 100 �g/lens,while most Group IV lenses deposit between 400 and 2000 �g/lens,depending on the quantification method and degree of ionicity ofthe material. Comparisons between hydrogel materials have shownthat the percentage of active lysozyme is typically >2× higher onionic materials, compared to non-ionic materials, as shown in bothin vitro [39] and ex vivo studies [85].

6. Silicone hydrogel contact lenses – the present

Pure silicone is a highly gas permeable material, but due to itshydrophobic character silicone-based contact lenses are poorlywettable [86] and show high rates of lipid deposition [76,87].

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56 D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64

Tab

le

1aQ

uan

tita

tive

dat

a

on

pro

tein

dep

osit

ion

to

pH

EMA

-bas

ed

con

tact

len

s

mat

eria

ls.

Mat

eria

l

Tota

l pro

tein

(�g/

len

s)Ly

sozy

me

(�g/

len

s)La

ctof

erri

n(�

g/le

ns)

Alb

um

in(�

g/le

ns)

In

vitr

o/ex

vivo

Sol t

ype/

extr

acti

on

met

hod

/qu

anti

fica

tion

met

hod

Exp

osu

reti

me

(day

s)

Gro

up

I[2

8]A

ll13

.6

±

16.8

Ex

vivo

Nin

hyd

rin

assa

y/sp

ectr

oph

otom

etry

Op

en[3

4]

N/A

74.5

±

5.7

Ex

vivo

Alc

ohol

, ure

a,

acet

ic

acid

/Bio

-Rad

assa

y

Op

en[3

4]N

/A86

.9

±

12

In

vitr

oA

TS/A

lcoh

ol, u

rea,

acet

ic

acid

/Bio

-Rad

assa

y1

[73]

N/A

4.5

±

2.0

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/C

oom

assi

ebr

illi

ant

blu

e1

[71]

Poly

mac

on

30

±

60

Ex

vivo

AC

N-T

FA

extr

acti

on/B

CA

anal

ysis

14[3

0]

Poly

mac

on

3.9

±

2.2

Ex

vivo

Hea

t,

SDS/

Low

ry

colo

rim

etri

c

test

Op

en[7

2]Po

lym

acon

16

±

8

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]

Poly

mac

on

23.2

±

9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[3

1]Po

lym

acon

3.2

±

0.7

In

vitr

oA

TS/A

CN

-TFA

extr

acti

on/H

PLC

, BC

A

anal

ysis

,SD

S-PA

GE

14

[4]

Poly

mac

on41

.1

In

vitr

oU

rea,

acet

ic

acid

/Bra

dfo

rd

assa

y2

[32]

Tefi

lcon

A

20.4

±

17

Ex

vivo

SDS

extr

acti

on/a

min

o ac

id

anal

ysis

Op

en

Gro

up

II[2

8]A

ll37

.7

±

135

Ex

vivo

Nin

hyd

rin

assa

y/sp

ectr

oph

otom

eter

Op

en[3

4]N

/A23

4.3

±

19

In

vitr

o

ATS

Alc

ohol

+ u

rea

+

acet

ic

acid

/Bio

-Rad

assa

y

1[7

3]N

/A

6.8

±

4.1

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/C

oom

assi

ebr

illi

ant

blu

e1

[78]

Alp

hafi

lcon

A

26

±

7

Ex

vivo

UV

spec

trop

hot

omet

ry

14[7

8]

Alp

hafi

lcon

A

40

±

7

Ex

vivo

UV

spec

trop

hot

omet

ry

28[7

2]A

lph

afilc

on

A44

.5

±

13In

vitr

oSi

ngl

e

sol/

rad

iola

beli

ng

14[7

2]

Alp

hafi

lcon

A

53.3

±

11

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[3

2]

Atl

afilc

on

A

6.8

±

5.6

Ex

vivo

SDS

extr

acti

on/a

min

o

acid

anal

ysis

Op

en[3

1]

Lid

ofilc

on

A

14.8

±

1.4

In

vitr

o

ATS

/AC

N-T

FA

extr

acti

on/H

PLC

, BC

A

anal

ysis

,SD

S-PA

GE

14

[84]

Lid

ofilc

on

A

2.2

±

0.1

In

vitr

o Si

ngl

e

sol/

rad

iola

beli

ng

3[7

5]

Net

rafi

lcon

A

87

Ex

vivo

UV

spec

trop

hot

omet

ry

90[7

2]O

mafi

lcon

A35

.3

±

8In

vitr

oSi

ngl

e

sol/

rad

iola

beli

ng

14[7

2]

Om

afilc

on

A

43.8

±

13

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[7

9]

Om

afilc

on

A

4.1

±

1.1

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

9]

Om

afilc

on

A

6.8

±

2.0

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[3

9]O

mafi

lcon

A68

±

28In

vitr

oSi

ngl

e

sol/

AC

N-T

FA

extr

acti

on/W

este

rnbl

otti

ng

17

[83]

Vas

urfi

lcon

A

42

±

7

Ex

vivo

SDS

extr

acti

on/s

pec

trop

hot

omet

ry

30[4

2]V

asu

rfilc

on

A28

±

20Ex

vivo

SDS

extr

acti

on/s

pec

trop

hot

omet

ry

30

Gro

up

III

[28]

All

33.2

±

73.6

Ex

vivo

Nin

hyd

rin

assa

y/sp

ectr

oph

otom

eter

Op

en[3

4]N

/A78

.5

±

2.1

2

sam

ple

son

ly!!

!Ex

vivo

ATS

/Alc

ohol

, ure

a,

acet

ic

acid

/Bio

-Rad

assa

y

N/A

[34]

N/A

151.

4

±

10.6

In

vitr

o

ATS

/Alc

ohol

, ure

a,

acet

ic

acid

/Bio

-Rad

assa

y

1[7

3]N

/A

5.8

±

0.8

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/C

oom

assi

ebr

illi

ant

blu

e1

[31]

Phem

filc

on

A

12.2

±

2.3

In

vitr

o

ATS

/AC

N-T

FA

extr

acti

on/H

PLC

, BC

A

anal

ysis

,SD

S-PA

GE

14

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D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64 57

Tabl

e

1a

(Con

tinu

ed)

Mat

eria

l

Tota

l pro

tein

(�g/

len

s)Ly

sozy

me

(�g/

len

s)La

ctof

erri

n(�

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ns)

Alb

um

in(�

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ns)

In

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o/ex

vivo

Sol t

ype/

extr

acti

on

met

hod

/qu

anti

fica

tion

met

hod

Exp

osu

reti

me

(day

s)

Gro

up

IV[2

8]

All

991.

2

±

472.

7

Ex

vivo

Nin

hyd

rin

assa

y/sp

ectr

oph

otom

eter

Op

en[3

4]

N/A

208.

7

±

137.

8

Ex

vivo

Alc

ohol

, ure

a,

acet

ic

acid

/Bio

-Rad

assa

y

Op

en[3

4]

N/A

322.

6

±

10.3

In

vitr

o

ATS

/Alc

ohol

, ure

a,

acet

ic

acid

/Bio

-Rad

assa

y

1[7

3]

N/A

4.0

±

1.8

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/C

oom

assi

ebr

illi

ant

blu

e1

[78]

Etafi

lcon

A

482

±

67

Ex

vivo

UV

spec

trop

hot

omet

ry

14

[78]

Etafi

lcon

A

493

±

101

Ex

vivo

UV

spec

trop

hot

omet

ry

28

[77]

Etafi

lcon

A

1341

.7

±

175.

5

Ex

vivo

AC

N-T

FA/L

owry

met

hod

, sp

ectr

oph

otom

etry

14[7

6]Et

afilc

on

A

985

±

241

Ex

vivo

AC

N-T

FA

extr

acti

on/S

DS-

PAG

E,

Wes

tern

blot

tin

g14

[75]

Etafi

lcon

A

707

Ex

vivo

UV

spec

trop

hot

omet

ry

14

[37]

Etafi

lcon

A

600

Ex

vivo

AC

N-T

FA

extr

acti

on/H

PLC

1[3

7]

Etafi

lcon

A

1300

Ex

vivo

AC

N-T

FA

extr

acti

on/H

PLC

11[7

1]

Etafi

lcon

A

3700

±

700

Ex

vivo

AC

N-T

FA

extr

acti

on/B

CA

14

[38]

Etafi

lcon

A

1413

±

247

2005

±

252

935

±

271

OFE

1551

±

371

Ren

u

MP

Ex

vivo

AC

N-T

FA

extr

acti

on/W

este

rn

blot

tin

g

30

[72]

Etafi

lcon

A

1433

.5

±

76

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]

Etafi

lcon

A

1434

.5

±

56

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[7

9]

Etafi

lcon

A

5.7

±

0.9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

9]

Etafi

lcon

A

11.3

±

1.9

In

vitr

o Si

ngl

e

sol/

rad

iola

beli

ng

28[3

5]

Etafi

lcon

A

427.

5

±

6.4

In

vitr

o Si

ngl

e

sol/

AC

N-T

FA

extr

acti

on/B

CA

assa

y

1[4

]

Etafi

lcon

A

30.1

In

vitr

o

Sin

gle

sol/

Ure

a

+

acet

ic

acid

/Bra

dfo

rd

assa

y

2[3

9]

Etafi

lcon

A

1800

±

600

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/W

este

rnbl

otti

ng

17

[3]

Etafi

lcon

A

2200

.3

±

15.6

0.2

±

0.04

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[3

1]

Etafi

lcon

A

554.

9

±

18.3

In

vitr

o

ATS

/AC

N-T

FA

extr

acti

on/H

PLC

, BC

A

anal

ysis

,SD

S-PA

GE

14

[75]

Vifi

lcon

A

82

Ex

vivo

UV

spec

trop

hot

omet

ry

30

[32]

Vifi

lcon

A

376

±

216

Ex

vivo

SDS

extr

acti

on/a

min

o

acid

anal

ysis

Op

en

[42]

Vifi

lcon

A

488

±

40

Ex

vivo

SDS

extr

acti

on/s

pec

trop

hot

omet

ry

30

[72]

Vifi

lcon

A

356

±

48

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]

Vifi

lcon

A

512.

3

±

51

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[1

28]

Vifi

lcon

A

598

±

184

In

vitr

o

ATS

/Nin

hyd

rin

assa

y/sp

ectr

oph

otom

eter

16

h

[84]

Perfi

lico

n

A

3.0

±

0.05

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

3[8

4]

Bu

filc

on

A

0.2

±

0.02

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

3[1

29]

Phem

filc

on

A

905

OFE

1025

Ren

uEx

vivo

AC

N-T

FA

extr

acti

on/H

PLC

90

AC

N-T

FA:

acet

onit

rile

/tri

flu

oroa

ceti

c

acid

, ATS

:

arti

fici

al

tear

solu

tion

, BC

A:

bici

nch

onin

ic

acid

, DTT

:

dit

hio

thre

itol

, FTI

R:

Fou

rier

tran

sfor

m

infr

ared

, HPL

C:

hig

h

per

form

ance

liqu

id

chro

mat

ogra

ph

y,

OFE

:

Op

tifr

ee

Exp

ress

, OFR

:O

pti

free

Rep

len

ish

, SD

S:

sod

ium

dod

ecyl

sup

hat

e,

SDS-

PAG

E:

sod

ium

dod

ecyl

sulf

ate

pol

yacr

ylam

ide

gel e

lect

rop

hor

esis

, sol

:

solu

tion

, UV

:

ult

ravi

olet

.

Author's personal copy

58 D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64

Silicone hydrogel lenses, which became commercially availablein 1999 combine the benefits of the hydrophilic, ion-transportingproperty of pHEMA and the high oxygen permeability of siloxane-groups [88,89]. To-date, a dozen silicone hydrogel materials aremarketed worldwide, with oxygen transmissibilities (Dk/t) rangingfrom 65 to 175 × 10−9 units. These lenses account for approxi-mately 39% of all newly fitted soft contact lenses worldwide [65].

Most silicone hydrogel lens materials require surface mod-ification to overcome the hydrophobic nature of the siliconecomponents, which impacts the distribution of the protein on thesurface and within the lens matrix [80]. Various plasma treatmentshave been used to improve the surface wettability of certain sili-cone hydrogel lenses [64,90].

Silicone hydrogel lenses have a more complex monomer compo-sition than pHEMA-based materials [63,64]. Components that arecommonly seen are DMA (N,N-dimethylacrylamide), PDMS (poly-dimethylsiloxane), TPVC (tris-(trimethylsiloxysilyl) propylvinylcarbamate), TRIS (trimethylsiloxy silane), proplvinyl carbamate,PVP and other siloxane macromers [64]. Due to the complex-ity of these materials, the following protein sorption profiles arereviewed by lens type rather than material groups.

6.1. Balafilcon A

A reactive gas plasma process transforms the hydrophobicsiloxane components on the surface of balafilcon A lenses intohydrophilic silicate compounds (‘glassy islands’) [64,91]. However,this surface modification is no barrier for lysozyme and albuminto penetrate into the matrix, as demonstrated by CLSM [3,80]. Bal-afilcon A is the only silicone hydrogel material considered ionic(FDA Group III) due to the incorporation of an ionic group (N-vinylaminobutyric acid), and it attracts more protein than all other sil-icone hydrogel lenses currently available [39,72,92]. Patient wornlenses deposit 5–34 �g of total protein [36,92,93], while lysozymeaccounts for approximately 32% [36] to 50% [93] of the totalamount of deposited protein. The amounts of individual proteinsdepositing on balafilcon A have been determined using in vitroexperiments, and indicate 10–50 �g of lysozyme [3,35,39,72,76],6–17 �g of lactoferrin [35,79] and less than 2 �g of albumin [3]per lens. Lysozyme activity on worn lenses and in vitro modelsis approximately 50% [38,39,76,93]. Choice of care regimen mayalso impact protein activity on these lenses: higher levels of dena-tured lysozyme have been found when lenses were cleaned with apolyhexanide-based system compared to a polyquaternium-basedsystem [38,76].

6.2. Lotrafilcon A, lotrafilcon B and sifilcon A

The contact lens materials lotrafilcon A and B are permanentlymodified by a gas plasma treatment using a mixture of trimethylsi-lane, oxygen and methane to form a 25 nm thin hydrophilic coatingover the surface [63,88,94]. This lens surface minimizes albuminand lysozyme penetration into the materials, with higher accumu-lations seen on the surface as determined by CLSM [3,52]. Despitethe similarity between both materials, lotrafilcon B, which has alower Dk/t and a higher water content compared to lotrafilcon A,seems to deposit slightly more protein. Quantitative analysis onworn lenses detected 5–7 �g/lens of total protein on lotrafilcon A[36,93], while <1–19 �g/lens has been reported for lotrafilcon B,with the majority of studies reporting >7 �g per lens [92,93,95–97].Ex vivo studies have further determined that lysozyme accountsfor <25% of the total protein deposited on worn lotrafilcon A and B[36,93].

In vitro studies on both lotrafilcon materials have confirmed theresults from ex vivo lenses, showing that slightly higher amountsof deposited protein are typically found on lotrafilcon B compared

to lotrafilcon A lenses: lotrafilcon A deposited 2–4 �g lysozyme[39,72,76] and 1–2 �g lactoferrin [79], while lotrafilcon B accu-mulated 4–10 �g of lysozyme [3,39,72] and 2–3 �g of lactoferrin[79]. Lysozyme activity on both lens types have been determinedto be ≤25%, while results typically show marginally, but statisti-cally insignificant, higher levels of active lysozyme on lotrafilcon Blenses [38,39,76,93].

Sifilcon A is manufactured using a lathe-cutting process and rep-resents the newest member of this “family” of materials. Ex vivoresults confirmed that the amount of protein depositing on thislens is similar to lotrafilcon A and lotrafilcon B, with 5 �g of totalprotein and 2 �g of lysozyme/lens being found after 90 days of wear[98]. The level of protein denaturation is also similar to the othertwo lens types, with 20% lysozyme activity for patient-worn lenses[98].

6.3. Asmofilcon A

The surface of asmofilcon A lenses is modified based on “Nano-glass” technology using a new plasma treatment, which combinesplasma coating and surface oxidation [99]. Although these lenseshave been available since 2007, no data on protein sorption havebeen reported as of to date.

6.4. Galyfilcon A and senofilcon A

High molecular weight chains of PVP are incorporated into galy-filcon A and senofilcon A lenses to enhance surface wettability ofthe lens on eye [100–104]. Both lens types are manufactured usingsimilar material components.

In vitro experiments have shown that lysozyme can penetrateinto the matrix of both lens materials after 24 h of incubationwith fluorescently conjugated protein [80]. Both lens types tendto deposit similar amounts of tear film proteins after wear. Thevalues reported range from <1 to 9 �g/lens, while slightly higheramounts are typically found on galyfilcon A lenses [36,40,92,93].The majority of studies report approximately 7 �g/lens of total pro-tein, of which lysozyme contributes <2 �g (∼25%) [36,93]. In vitrostudies have also confirmed that galyfilcon A, which has a lowerDk/t and a higher water content compared to senofilcon A, accumu-lates slightly more protein than senofilcon A [39,72,79]. Incubationin single protein solutions generally resulted in a higher proteinuptake in comparison to ex vivo studies, which can be explainedby the missing tear film components, which typically competewith proteins during the sorption process. In vitro studies of galy-filcon A and senofilcon A determined 8–17 �g and 6–13 �g oflysozyme/lens [39,72], respectively, while lactoferrin was found insimilar quantities on both lens types, at 3–5 �g/lens [79]. The activ-ity of deposited lysozyme on galyfilcon A lenses was 42–60%, whilea slightly lower percentage of 28–51% has been found for senofil-con A lenses [36,39,40,93]. However, so far none of these ex vivoand in vitro studies have shown a statistically significant differencebetween the two materials [36,39,40,93].

6.5. Narafilcon A and narafilcon B

These materials are modified using an internal PVP-based wet-ting agent (Hydraclear 1) and are used as single-use daily disposablelenses. Narafilcon A and B have been introduced fairly recently andas a result, no scientific data on protein deposition are available todate.

6.6. Comfilcon A and enfilcon A

These materials incorporate silicone which is based on siloxy-macromers instead of the commonly used TRIS-derivates [105].

Author's personal copy

D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64 59

Tab

le

1bQ

uan

tita

tive

dat

a

on

pro

tein

dep

osit

ion

to

sili

con

e

hyd

roge

l con

tact

len

s

mat

eria

ls.

Mat

eria

l

Tota

l pro

tein

(�g/

len

s)Ly

sozy

me

(�g/

len

s)La

ctof

erri

n(�

g/le

ns)

Alb

um

in(�

g/le

ns)

In

vitr

o/ex

vivo

Sol t

ype/

extr

acti

on

met

hod

/qu

anti

fica

tion

met

hod

Exp

osu

reti

me

(day

s)

SiH

y[1

30]

All

5.2

±

10

Ex

vivo

Ure

a,

SDS,

DTT

/BC

A, N

ano

Ora

nge

assa

y

14

and

30[3

6]

Bal

afilc

on

A

33.5

±

6.1

10.9

±

2.9

Ex

vivo

AC

N-T

FA

extr

acti

on/B

rad

ford

assa

y,

SDS-

PAG

E 14

[76]

Bal

afilc

on

A

10

±

3

Ex

vivo

AC

N-T

FA

extr

acti

on/S

DS-

PAG

E,

Wes

tern

blot

tin

g30

[38]

Bal

afilc

on

A

10

±

5.0

OFE

10

±

3.5

Ren

u

MP

Ex

vivo

AC

N-T

FA

extr

acti

on/W

este

rn

blot

tin

g 30

[93]

Bal

afilc

on

A

26.9

±

2.2

13.3

±

9.0

Ex

vivo

AC

N-T

FA

extr

acti

on/W

este

rn

blot

tin

g,B

rad

ford

assa

y14

[131

]

Bal

afilc

on

A

110.

1

±

26.1

Ex

vivo

AC

N-T

FA

extr

acti

on/B

CA

assa

y

14[9

2]

Bal

afilc

on

A

23.1

±

5.8

OFE

5.4

±

6.7

Aqu

ify

23.2

±

10.7

Cle

arC

are

17.6

±

6.1

OFR

Ex

vivo

Ure

a,

SDS,

DTT

/BC

A, N

ano

Ora

nge

assa

y

30

[35]

Bal

afilc

on

A

17

±

1.4

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/B

CA

assa

y

4

h[7

2]

Bal

afilc

on

A

10.6

±

1.6

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]

Bal

afilc

on

A

19.4

±

2.9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[7

9]B

alafi

lcon

A

6.3

±

1.1

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

9]B

alafi

lcon

A

11.8

±

2.9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[3

5]B

alafi

lcon

A

17

±

1.4

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/B

CA

assa

y

1[3

9]

Bal

afilc

on

A

44

±

10

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on, W

este

rnbl

otti

ng

17

[3]

Bal

afilc

on

A

50

±

0.1

1.9

±

0.4

In

vitr

o Si

ngl

e

sol/

rad

iola

beli

ng

14[3

6]

Lotr

afilc

on

A

6.7

±

2.7

0.7

±

0.5

Ex

vivo

AC

N-T

FA

extr

acti

on/B

rad

ford

assa

y,

SDS-

PAG

E

14[1

32]

Lotr

afilc

on

A

0.07

0.21

0.17

Ex

vivo

ELIS

A/p

erox

idas

e

con

juga

ted

anti

bod

ies

30[7

6]

Lotr

afilc

on

A

3

±

1

Ex

vivo

AC

N-T

FA

extr

acti

on/S

DS-

PAG

E,

Wes

tern

blot

tin

g30

[93]

Lotr

afilc

on

A

5.2

±

2.2

1.1

±

0.8

Ex

vivo

AC

N-T

FA

extr

acti

on/W

este

rn

blot

tin

g,B

rad

ford

assa

y14

[133

]

Lotr

afilc

on

A

0.7

rub

Com

ple

te2.

0

no

rub

OFE

Ex

vivo

Tert

-bu

tyl-

met

hyl

eth

er/F

TIR

30

[72]

Lotr

afilc

on

A

2.7

±

0.7

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]

Lotr

afilc

on

A

4.2

±

0.9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[7

9]

Lotr

afilc

on

A

0.7

±

0.7

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

9]

Lotr

afilc

on

A

2.1

±

0.9

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[3

9]

Lotr

afilc

on

A

2

±

1

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/W

este

rnbl

otti

ng

17

[95]

Lotr

afilc

on

B

9.8

±

1.4

Aqu

ify

9.8

±

1.0

Ren

u

ML

Ex

vivo

Ace

ton

e/B

rad

ford

assa

y

14–1

7

[93]

Lotr

afilc

on

B

6.6

±

3.4

1.4

±

1.1

Ex

vivo

AC

N-T

FA

extr

acti

on/W

este

rn

blot

tin

g,B

rad

ford

assa

y14

[92]

Lotr

afilc

on

B

3.6

±

1.0

OFE

0.3

±

0.9

Aqu

ify

0.5

±

0.4

Cle

arC

are

1.7

±

2.3

OFR

Ex

vivo

Ure

a,

SDS,

DTT

/BC

A, N

ano

Ora

nge

assa

y

30

Author's personal copy

60 D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64

Tabl

e

1b

(Con

tinu

ed)

Mat

eria

l

Tota

l pro

tein

(�g/

len

s)Ly

sozy

me

(�g/

len

s)La

ctof

erri

n(�

g/le

ns)

Alb

um

in(�

g/le

ns)

In

vitr

o/ex

vivo

Sol t

ype/

extr

acti

on

met

hod

/qu

anti

fica

tion

met

hod

Exp

osu

reti

me

(day

s)

[96]

Lotr

afilc

on

B

19

no

rin

se7

wit

h

rin

seEx

vivo

AC

N-T

FA

extr

acti

on/B

rad

ford

assa

y

5

[97]

Lotr

afilc

on

B

12.1

±

11.5

Ex

vivo

AC

N-T

FA

extr

acti

on/B

rad

ford

assa

y

14[7

2]

Lotr

afilc

on

B

3.7

±

0.6

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

2]Lo

trafi

lcon

B6.

1

±

1.3

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

28[7

9]

Lotr

afilc

on

B

1.7

±

0.6

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[7

9]Lo

trafi

lcon

B3.

1

±

1.0

In

vitr

oSi

ngl

e

sol/

rad

iola

beli

ng

28[3

9]Lo

trafi

lcon

B

6

±

3

In

vitr

o

Sin

gle

sol/

AC

N-T

FA

extr

acti

on/W

este

rnbl

otti

ng

17

[3]

Lotr

afilc

on

B

9.7

±

1.5

1.8

±

0.2

In

vitr

o

Sin

gle

sol/

rad

iola

beli

ng

14[1

31]

Lotr

afilc

on

B

2.6

±

3.8

Ex

vivo

AC

N-T

FA

extr

acti

on/B

CA

assa

y

14[9

8]Si

filc

on

A5.

3

±

2.3

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Author's personal copy

D. Luensmann, L. Jones / Contact Lens & Anterior Eye 35 (2012) 53– 64 61

Specific surface treatments or internal wetting agents are not usedin these lens types [105]. Since their launch in 2007, only one studyhas presented data on protein deposition with comfilcon A. In thisex vivo study a total of 8 �g protein/lens was determined, whichincluded <2 �g of lysozyme/lens after 25 days of wear [106].

6.7. Filcon II 3

Little is known about filcon II 3, which is currently only availablein Europe. It incorporates a surface wetting technology namedAquaGenTM, but no data on protein deposition rates have beenpublished to-date.

In summary, bulk material composition and surface modifi-cation methods vary greatly between silicone hydrogel lenses.However, the amount of protein deposition on these lens types isfairly similar and typically <10 �g/lens, with the exception of bal-afilcon A, which accumulates approximately three times as much(Table 1b).

7. Contact lens materials and surface modifications – thefuture

Silicone hydrogel materials have solved hypoxia-related com-plications and show low rates of protein deposition, but the relativeamount of denatured protein detected on these materials is typi-cally higher than that measured on pHEMA-based lenses [39,107].Furthermore, corneal inflammatory events tend to be equal orhigher with silicone hydrogel lenses compared to hydrogel lenses[108], which raises the question of whether surface engineeringtechniques or other material components can improve the biocom-patibility of these latest contact lens materials.

A number of different approaches to passivate synthetic ornatural biomaterials have been developed for blood contactingimplants, and some of these have been evaluated for contact lensmaterials [109].

Surface coatings containing phosphorylcholine (PC) havebeen used in various biomedical applications, as they showacceptable level of biocompatibility [110,111] and attract onlysmall amounts of protein [39,72,79,112,113]. Novel materialcompositions with 2-methacryloyloxyethyl phosphorylcholine(MPC) confirmed a decrease in protein deposition rates withincreasing amounts of PC [114,115]. The combination of MPCwith bis(trimethylsilyloxy)methylsilylpropyl glycerol methacry-late (SiMA) has recently been suggested as a potential sili-cone hydrogel contact lens material, as it reaches an oxygentransmissibility of >125 units [116]. An in vitro experi-ment with this material confirmed the relationship betweenincreased MPC content and reduced protein deposition rates,and these materials deposited less protein than senofilconA lenses [116]. In another study, a hydrogel lens materialwas synthesized using MPC with 2-(methacryloyloxy)ethyl-N-(2-methacryloyloxy)ethyl]phosphorylcholine (MMPC). This materialexhibited an oxygen permeability of 64 units, which is significantlyhigher than pHEMA, and the highly wettable surface depositedapproximately three times less protein than omafilcon A lenses[117].

Polyethers such as poly(ethylene glycol) (PEG) or poly(ethyleneoxide) (PEO) are currently used in various biomaterial applications,due to their hydrophilicity, bioinertness and resistance to proteinand cell adsorption [118,119]. In a recent clinical study, lotrafilconA lenses were coated with PEO using an allylamine plasma poly-mer interlayer and their in vivo performance was evaluated [120].The researchers confirmed good biocompatibility after 6 h of lenswear and reported that modified lenses attracted less than half the

amount of protein compared to non-modified lotrafilcon A lenses[120].

Crosslinking hyaluronic acid (HA) into pHEMA, siliconehydrogel-like materials or PMMA also reduces protein deposi-tion rates compared to non-treated materials [121–123]. PHEMAcrosslinked to HA of differing molecular weights accumulated sig-nificantly lower amounts of albumin and IgG compared to nelfilconA (FDA Group II) and the silicone hydrogel lens material senofil-con A [121]. Lysozyme was found in lower amounts on nelfilconA, but no difference between the HA-crosslinked materials andsenofilcon A was seen [121]. A strong lysozyme repelling effectwas also seen when HA was crosslinked to methacryloxy propyltris(trimethylsiloxy) silane (Tris)-pHEMA hydrogels, independentof the ratio between Tris:pHEMA [122].

Finally, other approaches for ophthalmic material/surfacedesigns use combinations of frequently used materials withperfluoropolyethers [124], polyvinyl alcohol [125] and surfacecoatings with pyrolytic carbon [126], albumin, elastin [109] orcationic peptide [127] to reduce protein accumulation and micro-bial adherence.

In conclusion, improvement in contact lens biocompatibility isan ongoing process and controlling the amount and conformationalstate of deposited protein remains one of the major challenges.The ocular surface environment is very complex, and tear filmcomposition varies greatly between individuals [14]. While thisreview has only dealt with protein deposition, it is known that sili-cone hydrogel lenses attract greater amounts of lipid compared tomany polyHEMA-based lenses [87], which is the opposite trendto that seen with protein accumulation. Increased lipid deposi-tion may impact clarity of vision, wettability and comfort, buthas not been associated directly with ocular surface inflamma-tory responses. Although silicone hydrogel lenses have significantlyreduced complications related to hypoxia [107] they have notreduced the prevalence of ocular complications such as inflamma-tion and microbial keratitis, and the role of material deposition tothese complications remains unclear [108].

Optimal biocompatibility with lens materials may not requirethe material to be resistant to all tear film components. Rather,it is important that the material is accepted by the ocular envi-ronment and this may require the deposition of selected tear filmcomponents. In respect to proteins, the ideal contact lens mate-rial should bind proteins only loosely, allowing the protein to bereadily removed when exposed to contact lens care regimens andmaintaining the native state of any bound proteins. New contactlens material designs and surface modifications are currently underinvestigation, but only the future will show whether or not they canprovide enhanced on eye biocompatibility.

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