Corneal Infiltrative Events (CIE) and Contact Lenses: Avoidable or Not?

Lyndon Jones PhD DSc FCAHS FCOptom FAAO FIACLE FBCLAProfessor & University Research ChairSchool of Optometry & Vision Science

Director, Centre for Ocular Research & Education (CORE)University of Waterloo, Ontario, Canada

Over the past three years, members of CORE have received research funding and/or honoraria from the following 15 companies & 3 funding agencies:

Lyndon Jones PhD, DSc, FCAHS, FCOptom, FAAO Financial Disclosures

• Alcon• Allergan• Contamac• CooperVision• GL Chemtec

• Inflamax Research• Johnson & Johnson Vision• Menicon• Nature’s Way• Novartis

• Safilens• Santen • Shire • SightGlass• Visioneering

3

Corneal Infiltrates vs Microbial Keratitis

• An infiltrate is a collection of inflammatory cells (usually polymorphonuclear leucocytes) located within the cornea

• located within the epithelium or subepithelial layers

• Self-limiting inflammatory response

Definition

1. Efron N: Contact Lens Complications. 3rd ed. 2012, Oxford: Elsevier.2. Steele & Szczotka-Flynn: Epidemiology of contact lens-induced infiltrates: an updated review. Clin Exp Optom 2017; 100;5: 473-481.

Stroma

Epithelium

Tears

Bowman’s

Stroma

Epithelium

Tears

Bowman’s

Intraepithelial infiltrates Subepithelial infiltrates (SEI)

• Infiltrates appear as small, hazy whitish areas often surrounded by edema • Can be single or diffuse

Appearance

1. Dumbleton: Adverse events with silicone hydrogel continuous wear. Cont Lens Anterior Eye 2002; 25;3: 137-46.2. Sweeney et al.: Clinical characterization of corneal infiltrative events observed with soft contact lens wear. Cornea 2003; 22;5: 435-42.3. Steele & Szczotka-Flynn: Epidemiology of contact lens-induced infiltrates: an updated review. Clin Exp Optom 2017; 100;5: 473-481.

Contact Lens Peripheral Ulcer (CLPU)

1. Grant et al.: Contact lens induced peripheral ulcers during hydrogel contact lens wear. CLAO J 1998; 24;3: 145-51.2. Holden et al.: Contact lens-induced peripheral ulcers with EW of disposable hydrogel lenses: histopathologic observations on the nature and type of corneal infiltrate. Cornea 1999; 18;5: 538-43.3. Hume et al.: Contact lens induced peripheral ulcers (CLPU) are produced by an alpha-toxin deficient mutant of Staph aureus. Investigative Ophthalmology & Visual Science 2001; 42;4: S593-S593.4. Dumbleton: Adverse events with silicone hydrogel continuous wear. Cont Lens Anterior Eye 2002; 25;3: 137-46.5. Wu et al.: The causes of and cures for contact lens-induced peripheral ulcer. Eye Contact Lens 2003; 29;1 Suppl: S63-6; discussion S83-4, S192-4.

Microbial Keratitis

• Infection of the cornea with pathogenic organism• most typically bacteria• associated inflammation and destruction of the cornea

• Sight-threatening ocular emergency• Variety of terms

• corneal ulcer• infectious keratitis• ulcerative keratitis• bacterial keratitis

Microbial Keratitis (MK)

• CL Wearers• 70% Pseudomonas aeruginosa (gram –ve)

• Non CL wearers• 50% Staph aureus (gram +ve)

• Emerging gram –ve pathogens 1,2• Achromobacter xylosoxidans• Delftia acidovorans• Stenotrophomonas maltophilia

Major microbial types in MK

1. Wiley et al., Bacterial biofilm diversity in contact lens-related disease: emerging role of Achromobacter, Stenotrophomonas, and Delftia. IOVS 2012. 53(7): p. 3896-905.2. Willcox et al., Contact lens case contamination during daily wear of silicone hydrogels. Optom Vis Sci, 2010. 87(7): p. 456-64.

• Acutely painful• increasing pain despite CL removal

• Patient may notice “white spot” on cornea• Redness• Discharge / tearing• Photophobia• Reduced vision• Swollen lid

Symptoms of MK

Sweeney et al.: Clinical characterization of corneal infiltrative events observed with soft contact lens wear. Cornea 2003; 22;5: 435-42.

• 23 year-old male• SCL wearer• Non compliant with care regimen• Red eye (OD) for 1 day• Significant pain & photophobia• Significant epiphora• Significant hyperemia• VA 6/12 OD, 6/5 OS

My 1st MK Case: 1986

Slit Lamp Appearance: 1986

My Last MK Case: 2016

Management: Scleral Lens Fit

• Lower risk than bacterial keratitis • 5-10% of all CL-related MK

• Acanthamoeba 1-4• Non-sterile water exposure (including swimming in CLs)• Poor compliance• CL solutions (US 2007; UK 2018)

• Fungal keratitis (mainly Fusarium) 5-7• Poor compliance• CL solution (global 2004-2006)

• formulation and storage conditions

Acanthamoeba & Fungal Keratitis

1. Szentmary et al.: Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol 2019; 31;1: 16-23.2. Arshad et al.: Water Exposure and the Risk of Contact Lens-Related Disease. Cornea 2019.3. Joslin et al.: The association of contact lens solution use and Acanthamoeba keratitis. Am J Ophthalmol 2007; 144;2: 169-180.4. Carnt et al.: Acanthamoeba keratitis in 194 patients: risk factors for bad outcomes and severe inflammatory complications. Br J Ophthalmol 2018; 102;10: 1431-1435. 5. Chang et al.: Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA 2006; 296;8: 953-63.6. Saw et al.: Risk factors for contact lens-related fusarium keratitis: a case-control study in Singapore. Arch Ophthalmol 2007; 125;5: 611-7.7. Bullock et al.: Effects of time, temperature, and storage container on the growth of Fusarium species: implications for the worldwide Fusarium keratitis epidemic of 2004-2006. Arch Ophthalmol 2011; 129;2: 133-6.

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Incidence

MK Rates for All CL Types(modern lenses)

DW RGP DW SCL DD SCL DW SH EW SCL EW SH0

20

40

60

80

100

120

Ann

ual I

ncid

ence

(per

10,

000)

2.96.4 4.9

0

96.4

19.8

1.2 1.9 2

11.9

19.525.4

Morgan 2005 Stapleton, 2008

Lowest for RGPHighest for EW

Severe keratitis and MK

MK Rates for EW SCL

Hydrogel ~ SiHy

MK Rates for DW SCL

No change over 25 years!

Willcox: Microbiology and CL wear. CL Spectrum April 2011

Incidence of MK with OK in Children• 1317 patients• 640 adults (49%) and 677 children

(51%) • 2599 patient-years of wear • Incidence

– 13.9 per 10,000 px years• Risk of MK with overnight corneal

reshaping contact lenses is similar to that with other overnight modalities

Bullimore et al.: The risk of microbial keratitis with overnight corneal reshaping lenses. Optom Vis Sci 2013; 90;9: 937-44.

• Difficult• depends upon criteria used for classification, lens type worn, frequency of visits and

quality of the observers in the study• Daily wear

• symptomatic• 0.5-3%

• asymptomatic• 3-5%

• Extended wear• symptomatic

• 2-6%• asymptomatic

• 20-25%

Annualised Incidence for IK

Steele & Szczotka-Flynn: Epidemiology of contact lens-induced infiltrates: an updated review. Clin Exp Optom 2017; 100;5: 473-481.

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Risk Factors

Relative Risk Factors For CIEFactor Relative Risk

Non-modifiable

Age (18-29) 2.2xYoung age (50) 2xMales 1.4xRefractive error > ± 5 D 1.2-1.6xPrevious history of CIE 2.5-6.1x

Modifiable

Smoking 1.4-2.7xOvernight wear 2.4-7xMultipurpose solutions 2.9-3.8xBacterial bioburden 5x (lids); 8x (lens)

Modified from Steele & Szczotka-Flynn: Epidemiology of contact lens-induced infiltrates: an updated review. Clin Exp Optom 2017; 100;5: 473-481

Question• Which soft lens material has been shown to provide

the lowest risk for the development of corneal infiltrates in reusable lenses?

a) Hydrogels b) Silicone hydrogelsc) No difference

Infiltrative Keratitis: Reusable CL• Consistently ~2X higher rate with

reusable SiHy 1-4

1. Szczotka-Flynn & Diaz: Risk of corneal inflammatory events with silicone hydrogel and low dk hydrogel extended contact lens wear: a meta-analysis. Optom Vis Sci 2007; 84;4: 247-56.2. Radford et al.: Risk factors for nonulcerative contact lens complications in an ophthalmic accident and emergency department: a case-control study. Ophthalmology 2009; 116;3: 385-92.3. Chalmers et al.: Age and other risk factors for corneal infiltrative and inflammatory events in young soft contact lens wearers from the Contact Lens Assessment in Youth (CLAY) study. Invest Ophthalmol Vis Sci 2011; 52;9: 6690-6.4. Chalmers et al.: Multicenter case-control study of the role of lens materials and care products on the development of corneal infiltrates. Optom Vis Sci 2012; 89;3: 316-25.

Study Rate with SiHy compared with hydrogel

1. Szczotka-Flynn & Diaz 2007 2.18 – 2.23x2. Radford et al 2009 2x3. Chalmers et al 2011 1.85x4. Chalmers et al 2012 1.84x

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Reducing CIE risk

Question• How much lower is the risk of developing corneal

infiltrates if a patient switches to daily disposable lenses from reusable lenses?

a) 2x b) 6xc) 12x

Infiltrative Keratitis & DD Contact Lenses

1. Chalmers et al.: Age and other risk factors for corneal infiltrative and inflammatory events in young soft contact lens wearers from the Contact Lens Assessment in Youth (CLAY) study. Invest Ophthalmol Vis Sci 2011; 52;9: 6690-6.

2. Chalmers et al.: Multicenter case-control study of the role of lens materials and care products on the development of corneal infiltrates. Optom Vis Sci 2012; 89;3: 316-25.

“12x lower risk of IK with DD lenses”

Infiltrative Keratitis & DD: Hydrogel vs SiHy• 1171 subjects (960 years of wear)

– 489 years of SiHyDD (1-Day Acuvue TruEye)– 471 years of HydDD (1-Day Acuvue Moist)

• Adverse events recorded and practice records reviewed• Only 1% had SCL complications that prompted visits to ECP• SiHy DD = HydDD• Risk factors associated with recorded events

– overnight wear = 30%– storage & reuse = 21%– >5.0D = 22%– Age

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Summary

Hydrogels vs SiHy• CIEs are a potential issue for CL wearers• Need to be able to differentiate between MK & IK

– careful slit lamp examination required• Be aware of the risk factors

– be careful of lens choice and modality with those who have higher risk factors

• Infiltrates lower with reusable hydrogels compared with reusable SiHy

• Infiltrates lowest with DD lenses

• Stop sleeping in lenses• Be wary of

• smokers• those in the age group 18-29• non-compliant males• previous inflammatory response• those exhibiting blepharitis or meibomian gland dysfunction

• higher levels of gram +ve bioburden on the lids

• Switch to peroxide• Switch to daily disposables• Improve compliance with respect to

• Water exposure• hand washing• case replacement & case cleaning

Reducing CIE Risk

Steele & Szczotka-Flynn: Epidemiology of contact lens-induced infiltrates: an updated review. Clin Exp Optom 2017; 100;5: 473-481.

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Foliennummer 1Lyndon Jones PhD, DSc, FCAHS, FCOptom, FAAO �Financial DisclosuresFoliennummer 3DefinitionAppearanceContact Lens Peripheral Ulcer (CLPU)Microbial KeratitisMicrobial Keratitis (MK)Major microbial types in MKSymptoms of MKMy 1st MK Case: 1986Slit Lamp Appearance: 1986My Last MK Case: 2016Management: Scleral Lens FitAcanthamoeba & Fungal KeratitisFoliennummer 19MK Rates for All CL Types�(modern lenses)MK Rates for EW SCLMK Rates for DW SCLIncidence of MK with OK in ChildrenAnnualised Incidence for IKFoliennummer 25Relative Risk Factors For CIEQuestionInfiltrative Keratitis: Reusable CLFoliennummer 29QuestionInfiltrative Keratitis & DD Contact LensesInfiltrative Keratitis & DD: Hydrogel vs SiHyFoliennummer 33Hydrogels vs SiHyReducing CIE RiskFoliennummer 36THANK YOU