SOLUTION TOXICITY IN SOFT CONTACT LENS DAILY WEAR IS ASSOCIATED WITH CORNEAL INFLAMMATION

1Vision CRC and Institute for Eye Research, Sydney, Australia, 2School of Optometry and Vision Science, University of New South Wales, Sydney, Australia

Isabelle Jalbert,1-2 Nicole Carnt,1 Serina Stretton,1 Thomas Naduvilath,1-2 Eric Papas1-2

BACKGROUND RESULTS

• Second generation silicone hydrogel materials are now targeting the daily wear (DW) market• Certain combinations of multipurpose solutions and silicone hydrogel lenses are associated with solution-based corneal staining1

• Toxic staining typically described as mild, transient, asymptomatic and not requiring cessation of lens wear1,2

PURPOSE

To determine the relationship between solution toxicity, cornealinflammatory events and ocular discomfort in soft contact lens(SCL) DW.

METHODS

• Retrospective analysis of 16 non-randomised interventional clinical trials• 609 subjects (1218 eyes); 2,352 study visits• Bilateral DW, monthly replacement• Visit schedule: baseline, 1 week (questionnaire only), 2 weeks, 1 month, 3 months• Regulatory (ethics) approval and Informed Consent obtained

Table 1:

Lens Types Lens Care Solution

Balafilcon A H2O2 (AOSept)

Etafilcon A Polyquarternium-1 (Optifree Express)

Galyfilcon A PHMB (AQuify)

Lotrafilcon A Alexidine (ReNu MoistureLoc)

Lotrafilcon B

Senofilcon A

Note: 16/24 possible permutations were trialed.

Solution toxicity = Diffuse punctate staining in at least 4/5 corneal areas.

FIgure 1:

Corneal Infiltrative Events classified according to Sweeney’s Guide toCorneal Infiltrative Conditions3

Table 2: DemogaphicsSubjects withToxic staining

Unaffected ControlSubjects

P-Value

N=77 N=532Age (Mean yr ± SD) 34 ± 11 34 ± 11 0.99Male : Female (%) 29 : 71 36 : 64 0.21Previous lens wear history (%)(none : existing lens wearer)

7 : 93 13 : 87 0.21

Subjects completed the study (%) 87 88 0.83Smokers : Non-Smokers (%) 8 : 92 10 : 90 0.68Ethnicity (%) (Asian : Non-Asian) 20 : 80 21 : 79 0.88

Table 3: Number and Types of Corneal Infiltrative EventsWith ToxicStaining

UnaffectedControls

Asymptomatic Infiltrates:Small focal infiltratesOccasional very slight diffuseinfiltrationMid-periphery to peripheryNo overlying punctate stainingNo associated conjunctival rednessNo symptoms

7 10

Asyptomatic Infiltrative Keratitis:As above WITH overlyingpunctuate staining and/orassociated conjunctival redness

1 1

Infiltrative Keratitis:Anterior stroma infiltrationRedness, irritation, occasionaldischargeOccasional overlying punctuatestaining

2 13

Table 4: Association between the frequency and type of corneal infiltrative events and toxicstaining among eyes

Toxic staininggroup

Unaffectedcontrol group

P-Value Odds Ratio 95% CL

All Infiltrates 6.7%(9/134)

2.3%(24/1049)

0.008 3.08 1.4 - 6.76

AsymptomaticInfiltrates*

6%(8/133)

1.2%(12/1037)

1.000 0.63 0.08 - 4.86

SymptomaticInfiltrates

0.8%(1/26)

1.3%(13/1038)

0.001 5.47 2.10 - 13.63

* Combines Asymptomatic Infiltrates and Asymptomatic Infiltrative Keratitis events

Types of Toxic Staining

Table 5: Association between the frequency of corneal infiltrative events and type of toxicstaining among eyes

Eyes with cornealinfiltrative events

P-Value Odds Ratio 95% CL

Eyes with diffuse toxicstaining

10.0%(7/70)

0.002 4.79 1.99 - 11.55

Eyes with peripheraltoxic staining

4.8%(3/62)

0.184 2.19 0.64 - 7.49

Association between individual trial rates of toxic staining and contact lens inflammatoryevent rates. H2O2 = hydrogen peroxide solution. MPS = multipurpose solution

Figure 2: Diffuse 53% of eyes Figure 3: Peripheral 47% of eyes

y = 0.0671x + 0.7589R2 = 0.1527

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Incidence rate of toxic staining(per 100 eye months)

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Figure 4:

• Toxic staining rates ranged from 0 to 22 per 100 eye months

Please rate your experience with the lenses on a scale of 1 to 10 where 1 = poor and 10 =excellent. Note: Visits where solution toxicity was noted were excluded.

6

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(*p<0.05)

SUMMARY AND DISCUSSION

• This study demonstrates that corneal infiltrative events are 3-timesmore likely to occur in eyes that experienced toxic staining than those thatdid not (Table 4). Possible aetiologies for the corneal infiltrates include: o A direct causal relationship with toxic staining stimulating corneal inflammation. o Weakening of the cornea’s natural defences against microbial, lens related and environmental challenges by the toxic staining damage.• A dose-response relationship was evident for studies usingmultipurpose solutions and not for studies using the hydrogen peroxidesolution, where toxic staining rates were generally low (Figure 4). X-Ray photoelectron spectroscopy of pre-soaked lenses indicates thatsubstances from multipurpose lens care solutions are adsorbed onto thesurface of contact lenses.4 The release of antimicrobial components ofmultipurpose contact lens solutions such as polyquarternium-1, PHMB,and alexidine following insertion is the likely cause of damage to thesuperficial corneal epithelium.• No association could be demonstrated between demographic factorssuch as age, gender, previous CL wear experience, smoking or ethnicityand toxic staining rates (Table 2). Time of day of examination2 and lengthof cumulative exposure time1 were not controlled for in this study and areknown to impact the ease of toxic staining detection and should thereforebe considered in future analyses.• Whilst there was an apparent increase in the risk of developinginfiltrates when asymptomatic events were considered separately fromsymptomatic events (Table 4), the confidence intervals overlap andtherefore any hypothetical differences in association are inconclusive.Similarly, the apparent increased risk from the diffuse staining type eventswhen considered separately from peripheral staining events cannot beconsidered significant (Table 5).• Contrary to general belief,1 subjects experiencing solution toxicityreport lower average comfort ratings than those who do not (Figure 5).Practitioners may inadvertently be limiting the comfort of their patients ifthey are not alert to the possibility of solution toxicity.

CONCLUSION

Subjects that experience solution toxicity are more at risk of developing acorneal infiltrative event. Although these events were generally mild andasymptomatic, the potential for more serious sequelae means that if toxiccorneal staining is detected, alternative solution/lens type combinationsought to be investigated to reduce the general level of staining, lower therisk of inflammation and at the same time increase the general level ofcomfort.

REFERENCES1. Jones L, MacDougall N, Sorbara L. Asymptomatic corneal staining associated with the use of balafilcon silicone-hydrogel contact lenses disinfected with a polyaminopropyl biguanide-preserved care regimen. Optom Vis Sci. 2002;79:753-761.2. Garafolo R, Dassanayake N, Carey C et al. Corneal staining and subjective symptoms with multipurpose solutions asa function of time. Eye & Contact Lens. 2005;31:166-74.3. Sweeney DF, Jalbert I, Covey M et al. Clinical characterization of corneal infiltrative events observed with soft contactlens wear. Cornea. 2003;22:435.42.4. Phillips B, Jalbert I, Papas E et al. Adsorption of lens care products can affect the comfort of silicone hydrogel lenses.Clin Exp Optom. 2006;89:114.

ACKNOWLEDGEMENTSThis work was supported in part by the Australian Government (CRC scheme). The authors thank Ms Hanna Borchert forphotography of Figures 2 and 3.

Figure 5:

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