Are Adverse Events On The Decline?

Loretta B. Szczotka-Flynn, OD, MS, FAAO Dr. Loretta Szcotka-Flynn is an Associate Professor at Case Western Reserve University Department of Ophthalmology and Director of the Contact Lens Service at University Hospitals of Cleveland in Cleveland, Ohio since 1992. She is a Diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry and Diplomate Award Chair for the Section. She is serving a second term on the editorial board for Optometry and Vision Science and she is a Contributing Editor for Contact Lens Spectrum and Review of Optometry. Her research interests include contact lens oxygen permeability, extended wear, silicone hydrogels, keratoconus, post-surgical contact lens fittings and corneal topography. She has written 28 peer reviewed manuscripts and 9 book chapters. She served as the Principal Investigator at the Case Department of Ophthalmology Participating Clinic for the National Eye Institute sponsored study: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study from 1996 to 2004. She serves as a Principal Investigator for clinical trials from major contact lens companies and she continues to consult and test new products for industry. She was Ohio’s 1997 Young Optometrist of the Year, and she received the Nissel Award for excellence in rigid contact lens research in London, England in November 2000. In 2004, she received a Patient Oriented Research Career Development Award from the National Eye Institute to study longitudinal changes with silicone hydrogel lenses. She is also the recipient of two Ezell Fellowships for the years 2004-05 and 2005-06 from the American Optometric Foundation.

The classification, incidence, and prevalence of adverse events associated with silicone hydrogel contact lens wear depends on how one defines an adverse event. What qualifies as an adverse event? By some Institutional Review Board definitions, an adverse event can range from any condition that disrupts routine daily living activities without major discomfort and interferences that do not persist, to death. To that end, an asymptomatic clinician-observed slit lamp sign that necessitates temporary discontinuation of lens wear would be classified as an adverse event. Therefore, one may ask, has the incidence of unwelcome biomicroscopy signs such as neovascularization, epithelial microcysts, stromal edema, and polymegathism decreased since the introduction of silicone hydrogel lenses? Alternatively, once may ask the question whether traditionally defined adverse events have declined with silicone hydrogel lens use. These contact lens associated adverse events include symptomatic ocular surface changes such as infection, inflammation, and mechanically induced complications. Most of the adverse findings reported in the literature are secondary to extended wear contact lens use, therefore, I will concentrate on these findings unless otherwise mentioned.

In response to the first question: “Have adverse biomicroscopy findings declined with silicone hydrogel contact lens use?”; the answer is almost an unanimous “YES”! The clinical performance of silicone hydrogel lenses clearly demonstrates an improvement compared to low Dk lenses on a number of physiological markers making them especially desirable for continuous wear. Limbal

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Figure 1, central corneal staining observed with silicone hydrogel lens wear

hyperemia is not induced or, if present, is significantly reduced with silicone hydrogel lens use.[1] Limbal neovascular vessels induced from traditional hydrogels empty after refitting with silicone hydrogels.[2] There is no increased epithelial microcyst response.[3] No endothelial cell stress is observed [4] compared to studies of traditional hydrogels that show up to 22% increases in endothelial polymegathism.[5, 6] However, with daily wear use a new dilemma has presented itself secondary to unanticipated interactions of some silicone hydrogel lens materials and preserved multi-purpose solutions. Unacceptable levels of asymptomatic corneal staining can occur which necessitates alteration of the lens-solution combination.[7](Figure 1) As of yet, asymptomatic corneal staining has not been universally considered as an adverse event, but if lens wear is discontinued for a period of time to manage it, one can think of it as a type of an adverse response. Recently, two studies have associated corneal staining as a risk factor for corneal infiltrates[8, 9], thus more attention may now be paid to this biomicroscopy finding by clinicians and researchers alike.
In response to the second question: “Have infections, inflammation, and mechanical events declined with silicone hydrogel lens use?”; the answers are not as clear nor are they as positive. Case reports of microbial keratitis with silicone hydrogel lenses are still being reported in the literature.[10-13] Corneal infiltrates continue to occur, and contact lens papillary conjunctivitis (CLPC) continues to be present in different forms, time points, and rates compared to traditional hydrogel extended wear.[14, 15]

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Figure 2, localized CLPC after one month continuous wear of a silicone hydrogel lens in a neophyte patient

Microbial keratitis (MK)
In 1989 the U.S. Food and Drug Administration (FDA) reverted 30 day continuous wear approvals to 7 day extended wear for lenses made of low oxygen permeable (Dk) materials secondary to published reports that the risk of ulcerative keratitis was significantly higher when lenses were worn overnight.[17, 18] Schein et al[17] reported overnight users of low Dk lenses had a 10-15X greater risk of ulcerative keratitis compared to daily wearers, and Poggio et al[18] reported the annualized incidence of ulcerative keratitis was 20.9 per 10,000 lens wearers when worn for 7 days extended wear. Other studies confirm these rates for low Dk materials.[19, 20]

One of the early epidemiological studies to assess the impact of silicone hydrogel lens use compared to low Dk lenses on the risk of severe keratitis, suggested about a 5-fold decline in the silicone hydrogel group. [21] However, other studies to assess the risk of MK with silicone hydrogel lenses [22] documented the annual rate was 18 per 10,000 wearers for a 30 night CW schedule, similar to that reported for low Dk conventional and disposable extended wear lenses worn for fewer consecutive nights. Other groups have reported similar findings.[23] One study found the overall incidence of contact lens-related keratitis which required hospital treatment was about the same for silicone hydrogel and low Dk extended wear, however, the clinical severity of the keratitis was lower in the silicone hydrogel group compared with the low Dk group.[21, 24] Therefore, the general consensus is that silicone hydrogel lenses when worn for up to 30 days continuous wear do not reduce the risk of MK compared to low Dk lenses when worn for approximately 7 days of wear.

Corneal Infiltrates
Corneal inflammatory events are a result of a stimulus that has caused directed infiltration of leukocytes into the cornea.[25] (Figure 3) Two studies have assessed the prevalence and/or incidence of corneal infiltrates in non-contact lens wearers.[26, 27] Hickson reported the prevalence of subepithelial microinfiltrates to be 4% of non-contact lens wearing patients[26] and Sankaridurg reported 1.6% of eyes had asymptomatic infiltrates at baseline of a longitudinal study enrolling non-contact lens wearing myopes in India.[27] Nonetheless, it is well documented that extended wear use of contact lenses significantly increases the risk.

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Figure 3, infiltrative keratitis in a silicone hydrogel wearer

Reports of corneal infiltrates with silicone hydrogel lenses reported around the globe vary greatly depending on the definition and study design used to capture the infiltrative event. The incidence proportions range from 2% to over 21%.[28-35] A recent meta-analysis determined that the risk of corneal infiltrates is approximately two-fold higher in SH lenses when worn for 30 days continuous wear compared to their low Dk counterparts when worn for 7 days continuous wear.[36] In this meta-analysis the rates of infiltrates for low Dk hydrogels and silicone hydrogel lenses were 7.7 (2.2, 26.7) and 14.4 (4.3, 48.2) per 100 eye-years, respectively. However, it should be pointed out that the increased risk cannot be definitively linked to the effect of lens material because the effect of material on outcome is confounded by length of wear.

Summary
Most published studies of silicone hydrogel lens related adverse events include patients wearing lenses for up to 30 days continuous wear, and low Dk lenses for up to 7 days of wear. The rates of hypoxic related problems are significantly decreased with silicone hydrogel lens use. The risk of microbial keratitis is unchanged, but the severity of the infection may be lower with silicone hydrogel lens use. Rates of mechanical events may be unchanged or slightly higher in silicone hydrogel lenses, and the appearance of CLPC differs in silicone hydrogel lens wear. Sterile infiltrates have approximately doubled compared to low Dk lenses. It is hypothesized by some that a 30 day wear schedule with silicone hydrogel lenses may predispose the patient to some of these adverse events more than the material. Based on the vast ocular physiological improvements documented with highly oxygen transmissible silicone hydrogel materials, the quick recovery of mechanical problems, the relatively low severity of corneal inflammatory events, and the fact that many of the sterile corneal infiltrates are asymptomatic and possibly a normal ocular response to the environment, I continue to promote silicone hydrogel lenses as the lens of choice for extended wear and daily wear. However, new generation materials and perhaps a shortened length of wear should be investigated to continue to reduce adverse events to lower levels than that seen with low Dk materials.

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2. Dumbleton, K., Richter D, Simpson, Fonn D., A Comparison of the Vascular Response to Extended Wear of Conventional Lower Dk and Experimental High Dk Hydrogel Contact Lenses. Optom Vis Sci, 1998. 75(12s): p. 170.
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