The Current State of Extended Wear

By Arthur B. Epstein, O.D., F.A.A.O.
November 1999

We've come a long way with extended wear contact lenses. Now the only question that remains is: Is it safe?

As we embark upon the next century, our patients face a bewildering array of vision correction options. Extended wear contact lenses have again become one of them. The question is, will they remain a viable option?

The risks associated with previous generation extended wear contact lenses are well recognized and have been extensively reported. However, the risks associated with refractive surgery remain largely unknown. As refractive surgery's risks become more apparent, extended overnight contact lens wear has the potential to once again become an attractive alternative for many patients.

Extended lens wear offers reversibility at will, the ability to easily modify prescriptions and, from the patient's perspective, convenience. New hyper-Dk soft and rigid lens materials hold tremendous promise for fueling the anticipated resurgence of interest in extended wear. But before extended wear can regain wide acceptance, one important question needs to be answered: is it safe?

Assessing the Risk Factor

Years of negative reports in the professional and lay press have convinced the current generation of contact lens wearers and fitters that overnight wear is dangerous. In explaining these risks to our patients, it's important to realize that virtually all of our current extended wear clinical experience comes from technology that dates back two decades.

In 1995, Myers and Weiss reported on the comparative risks of extended wear and found that the risks associated with extended soft contact lens wear (of first-generation lenses) are two to 10 times less than the risks for nonfatal, serious and disruptive occurrences in a general population. Comparing these findings to more contemporary data on refractive surgery complication rates, the risks associated with first-generation extended wear lenses appear to be equal to or less than the risks associated with refractive surgery.

While extended wear has languished in clinical practice, numerous developments have broadened our understanding of related basic and clinical sciences to include new insight into corneal physiology, a better understanding of the mechanisms of infection in contact lens wearers and the development of improved materials and technology. These advances have served as the basis of an improved generation of extended wear contact lenses that may well have a decided safety advantage over refractive surgery.

In the early and mid-1980s, extended wear was in its heyday. It wasn't until the late 1980s that reports of serious problems surfaced in the media, causing a substantial decline in extended wear fitting. After intense scrutiny, overnight wear has been implicated as a causative factor of a variety of contact lens complications. While the methodology and results of some studies are questionable, their conclusions are not. Extended wear, particularly overnight wear of lower-Dk soft contact lenses, holds significantly greater risks for patients than daily wear.

Despite the relatively low incidence of microbial keratitis and the even lower risk of significant vision loss, the apparent causal relationship of contact lens wear to microbial keratitis, combined with the relative infrequency of microbial keratitis in the general population, has made extended wear complications a public health issue. This issue has prompted a reduction in recommended wearing schedules from 30 days to a maximum of 7 days in the United States and resulted in a general wariness of extended wear among eyecare practitioners.

While a relationship between extended contact lens wear and contact lens complications clearly exists, no study has successfully identified specific causal factors that can be altered to reduce the incidence of complications. This fact has been a frustrating obstacle in the development of safer extended wear lenses. Despite this, significant strides have been made in understanding the physiologic and microbiologic changes that occur in extended wear.

Hypoxia and Corneal Swelling

Lens induced hypoxia has long been considered a critical factor in extended wear complications. Indeed, hypoxia related corneal swelling was among the first reported adverse effects associated with contact lens wear. The corneal swelling and deswelling response to overnight closed-eye contact lens wear varies significantly between individuals depending on age and prior adaptation to contact lens wear. Individual response to hypoxia may be a factor in the genesis of lens related complications. Corneal swelling and deswelling responses after overnight wear are directly affected by oxygen transmissibility (Dk/t) levels. PMMA lenses worn overnight produce the greatest degree of corneal swelling and require the most prolonged recovery times. High-Dk RGPs and next-generation soft lenses show amounts of swelling on the eye nearly identical to those observed in the morning after sleeping without lenses.

In 1993, William Joe Benjamin, O.D. defined clinically relevant categories of contact lens transmissibility. Current lens materials falling in the "super" and "hyper" ranges, having equivalent oxygen potentials (EOPs) of 15 percent and higher, produce minimal corneal swelling and rapid recovery in the majority of patients.

Effects on the Corneal Epithelium

Over the past decade, researchers have begun to suspect that hypoxic corneal swelling is only part of a more complex picture. Corneal edema is a sentinel sign of hypoxic distress, however, this does little to explain the increased rate of complications associated with extended wear (Fig. 1). Much research has been directed at finding the "missing-link" between hypoxia and clinical complications. To date, no definitive findings have been found.

Disruption to the epithelial barrier may also cause complications. A significant proportion of corneal metabolic activity is devoted to the maintenance of epithelial integrity. Hypoxia, especially when prolonged and chronic, may induce epithelial barrier compromise. Theoretically, this could increase the cornea's susceptibility to toxins and pathogens.

Changes in epithelial permeability after closed eye overnight extended soft lens wear have been measured using fluorophotometry. However, these studies have been inconclusive. While increased epithelial permeability was found, no significant difference between extended and daily wear lenses was demonstrated. Moreover, when testing lower-Dk lenses, hypoxia alone did not appear to be a significant influence, suggesting that other factors such as reduced tear exchange or corneal acidosis may also play a role. Of greater significance, higher-Dk/t lenses (Dk/t > 80) produce no barrier function compromise with overnight lens wear.

In-vivo tandem scanning confocal microscopy (TSCM) has been used to non-invasively explore corneal changes associated with contact lens wear, especially changes in the surface epithelium. TSCM was used to evaluate superficial epithelial cellular desquamation after overnight RGP wear. Researchers found that the severity of desquamation is dependent on the oxygen transmissibility of the lens worn. With midrange-Dk/t lenses, surface damage occurs in the absence of residual overnight corneal swelling. However, higher-Dk/t lenses caused neither swelling nor damage.

Ichijima and coworkers used TSCM and tear lactate dehydrogenase (LDH) assay, an enzyme associated with anaerobic glycolysis, to non-invasively assess the effect of contact lens wear on ocular surface epithelial cells. They found a direct correlation between cell swelling, LDH levels and lens oxygen transmissibilities and concluded that even napping with lenses of a Dk/t of less than 20 could result in severe corneal damage. Increased LDH levels in extended wear soft contact lens patients had previously been reported.

Using specular microscopy, increases in epithelial cell area following extended soft contact lens wear have been found. The effects were partially reversible after lenses with greater permeability were fitted. Changes in epithelial cell morphology were proportional to the length of continuous lens wearing time. Epithelial microcysts associated with extended wear have also been related to lens oxygen transmissibility levels (Fig. 2).

Endothelial and stromal changes have been linked to extended wear induced corneal hypoxia. Endothelial blebs are a reversible, short-term response found on the corneal endothelium after contact lens wear. Although the number of blebs varies for each patient, there appears to be an inverse correlation between the number of blebs and the Dk/t of the contact lens worn. Bleb formation may be associated with corneal acidosis due to increased carbon dioxide and lactic acid build-up.

Epithelial homeostasis is also affected by hypoxia since the corneal epithelium is in a continual state of renewal. The basal cell layer gives rise to new epithelial cells, which move toward the surface, where they are desquamated. Our understanding of this homeostatic process has recently broadened to include a specialized population of cells at the limbus called slow cycling stem cells. These limbal stem cells are believed to be progenitors of basal cells. Damage to the stem cell population may be irreversible and can have disastrous consequences for the health of the epithelium and the eye.

A recent paper by Ren, Petroll, Jester and Cavanagh suggests that epithelial homeostasis may be disrupted by extended wear. They found up-regulation of limbal epithelial stem cell proliferation with a concomitant decrease in the proliferation of basal epithelial cells in a rabbit extended wear model. These findings appear to be linked to the oxygen transmissibility of test lenses. The authors speculate that decreased basal cell activity might explain the central epithelial thinning that had previously been associated with extended wear, and also hypothesize that increased stem cell activity is a compensatory mechanism for decreased central basal cell activity. Disturbingly, one possible result is depletion of the stem cell reservoir. The proliferation of limbal stem cells may also explain the limbal epithelial hypertrophy originally described by Kame as well as other extended wear peripheral findings.

Decreased limbal injection has been reported with higher-Dk lenses. Minus lenses can cause significant decreases in peripheral oxygen transmissibility. Local hypoxia has been linked to peripheral vascular invasion of the cornea, which can lead to a variety of complications. Increased limbal vascularization may also up-regulate the peripheral cornea immune response and increase the risk of corneal infiltrates. Increased colonization of Streptococcus pneumoniae has been linked to extended wear and corneal infiltrates.

Extended Wear and Infection

Perhaps the most interesting research conducted involves the microbiology of extended wear. Contact lens oxygen transmissibility has been shown to strongly correlate with Pseudomonas aeruginosa (PA) binding to epithelial cells after overnight lens wear in rabbit corneas. After extended soft lens wear (in humans), shed corneal epithelial cells irrigated from patients' eyes have shown an increased binding of PA compared to controls. More recently, a relationship between contact lens oxygen permeability and binding of PA to shed human epithelial cells was reported. Physical oxygen transmissibility rather than lens type was the primary factor determining PA binding compared to non-lens wearing controls.

The rate of surface epithelial cell shedding is reportedly decreased by corneal hypoxia. While short-term hypoxia down-regulates cell desquamation, Ren and co-workers found no increase in PA binding to these cells. They hypothesize that prolonged hypoxia and other factors present with lens wear are necessary precursors of increased PA binding. Indeed, Harding and associates found that short-term extended lens wear produced minimal detectable changes in the potential of corneal epithelial cells to bind bacteria. This finding suggests that long-term hypoxia in combination with lens wear is necessary for bacterial binding to occur. Surface changes to the superficial epithelium and the glycocalyx layer reported in extended wear may facilitate the binding of bacteria. Epithelial cell shedding is a recognized defense mechanism against infection. Prolonged bacterial contact time due to decreased cell shedding may be a factor in PA infection.

Contact lenses themselves may also contribute to infection by blocking the acute polymorphonuclear leukocyte (PMN) response to PA infection. Normally, infection produces massive PMN accumulation in infected corneas as an early host inflammatory response. Soft lens wear seems to act as a barrier for PMNs and may increase infectivity. Hence, tear exchange may play a role in the genesis of infection.

New Directions

Manufacturers are committed to the safety of the next generation of extended wear contact lenses. Bausch & Lomb was the first to introduce a high-Dk soft lens in the U.S. market with the 110 Dk/t PureVision (Balafilcon A) lens. PureVision is currently FDA approved for 7-day extended wear and is in clinical trials for 30-day extended wear. CIBA Vision is currently in 7-day and 30-day FDA clinical trials with their 175 Dk/t Focus Night and Day (Lotrafilcon A) lens in the U.S. Years of experience and clinical testing have shown these lenses to be extraordinarily safe.

Our patients currently have far more choices for refractive correction than ever before. Although time will tell, the latest generation of extended wear contact lenses and our improved understanding of the cornea and ocular surface promise to make this modality a viable option for years to come.