The Holy Grail

The contact lens industry has seen enormous growth over the past 30 years arising from the research, development and subsequent improvements in lens materials and manufacturing technology. In 1970 there were 2 million contact lens wearers worldwide, in 1986 there were 25 million, and today there are 95 million. Yet despite these improvements, patients are still searching for the ultimate method of vision correction, with many now looking to laser surgery or other alternatives to permanently correct their sight.

Continuous Wear (monthly rather than weekly) has long been the 'Holy Grail' of contact lenses, aiming to fulfill the desire of patients for immediate comfort, convenience, and excellent vision. Practitioners need such lenses to provide unaltered corneal physiology, minimal risk of adverse reactions and no microbial keratitis. In surveys conducted by the Cornea and Contact Lens Research Unit (CCLRU) and the Cooperative Research Centre for Eye Research and Technology (CRCERT), patients have overwhelmingly indicated their desire for 'permanent' vision correction, with 97 per cent expressing the desire to be able to wear contact lenses continuously for at least six nights per week. Though patients thought that initial comfort and quality of vision were the most important features in their choice of the contact lens they wore, 85 per cent believed that extended wear was an essential feature in choosing contact lenses as a method of vision correction[1].

The Elimination of Contact Lens Induced Hypoxia

In the early 80s, George Mertz and I (with considerable help from a then young researcher named John McNally), observed that if we had lenses with Dk/t over 87, contact lens induced overnight edema could be avoided[2,3]. We now have such lenses - two silicone hydrogels and at least one RGP. The silicone hydrogel lenses provide similar immediate comfort, fitting performance and surface characteristics to current disposable soft contact lenses, but they have also virtually eliminated hypoxia and its associated changes of corneal structure and function.

Overnight edema levels with the new generation materials are similar to the levels seen with no lens wear and are far lower than those with commercially available disposable soft lenses[4,5]. A number of other markers of hypoxic stress have been monitored in clinical studies at CCLRU/CRCERT and the Centre for Contact Lens Research (CCLR) at the University of Waterloo, Canada. For example, contact lens induced corneal striae[5], microcysts[6] (the classic marker of epithelial hypoxia) and CL induced endothelial polymegethism are rarely if ever seen with silicone hydrogel compared with disposable lens contact lens wear[5]. Corneal exhaustion syndrome should be a problem of the past.

Corneal striae observed in low Dk EW.	Typical appearance of microcysts observed in low Dk EW.

We also find remarkably 'white eyes' with silicone hydrogel lens wearers due to the reduction in limbal hyperaemia, elimination of limbal vascularisation and even "ghosting" of vessels in previous wearers of Low Dk EW soft lenses due to emptying of the vessels[7, 8]. Patients and practitioners actually remark about the obvious lack of redness. Myopic shifts observed with disposable hydrogel EW do not occur with silicone hydrogel extended wear lenses[9].

Typical very slight limbal redness during high Dk EW.	Typical moderate limbal redness during low Dk EW.

Overwhelming Patient Enthusiasm

CCLRU/CRCERT patients who have worn silicone hydrogel lenses successfully for 12 months or longer report overwhelming satisfaction with CW, 93% rating the lenses as excellent[1]. The main reason for their satisfaction with the CW system was its convenience i.e. the elimination of the need for care and maintenance and lens handling (88 per cent), being able to see in the morning (7 per cent) and excellent comfort (5 per cent). Ten per cent of patients reported that they forgot that they were wearing lenses at all.

Prior to having tried CW, two-thirds of these patients had considered refractive surgery to permanently correct their vision. Following their experiences with CW only 32% of these patients would still consider refractive surgery 'even if it were perfect'. Once CW has been successfully experienced there is a very strong preference for this form of 'permanent' vision correction. Similar results were found in CCLR surveys.

The public have always been ready for extended wear, it is the lenses that have not delivered in the past.

Is Loads of Oxygen Enough for The Perfect Lens?

No it is not - we aren't there yet. Studies at CCLRU/CRCERT and CCLR of adverse responses (ARs) with the new lenses compared to Low Dk lenses have shown that while hypoxia-related conditions are alleviated, currently there are similar rates of inflammatory conditions such as Contact Lens-induced Peripheral Ulcers; Contact Lens-induced Acute Red Eye; Infiltrative Keratitis and generalised Contact Lens Papillary Conjunctivitis. Other adverse events due to mechanical trauma (e.g. Superior Epithelial Arcuate Lesions and localised Contact Lens Papillary Conjunctivitis) have similar or higher incidence rates[1].

Typical fluoroscein staining observed in Superior Epithelial Arcuate Lesions.	Localised Contact Lens Papillary Conjunctivitis.	Generalised Contact Lens Papillary Conjunctivitis.

But these adverse responses are not sight threatening, just annoying, sometimes worrying and painful and relatively easily managed by practitioners.

Patient and Practitioner Education

The most important thing is for the practitioner and the patient to be aware of the signs and symptoms of these ARs, to recognise that they are treatable or manageable and require patients to be taught to check their eyes every day. They should ask themselves "Do my eyes look good? Do my eyes feel good? Do my eyes see well?" and if the answer is no to any of these questions, they should contact their eyecare practitioner.

The practitioner in turn needs to be able to accurately identify and manage the conditions, and to have the confidence to continue CW where appropriate.

The Slow Uptake of CW and Practitioner Fears

Despite the interest of the public in such lenses, the publicity surrounding their launch, the positive physiology and wearer enthusiasm, the uptake of CW lenses into the market has been comparatively slow (Figures 1 and 2). The major reason is practitioner fear.
(Figures 3 and 4)

Practitioners have seen and heard many past claims of the safety and efficacy of extended wear lenses, only to be disappointed. They are therefore understandably wary of the latest claims. Recent practitioner surveys at conferences in Britain, Australia and Sweden show that fears of infection and adverse responses are significant inhibitory factors with regard to EW. Practitioners' lens of first choice for uncomplicated myopes is still overwhelmingly daily wear, especially daily disposable lenses.

However, despite some current hesitation regarding the high Dk EW lenses, we strongly believe the future for the lenses still looks extremely promising. With the existing complication rates for refractive surgery, and as the effects of surgery on long term ocular health are still unknown, more and more practitioners and patients are now looking to EW to provide convenient 'permanent' vision correction without surgical risks.

The Risks of Microbial Keratitis

When Steve Zantos and I conducted our first Extended Wear (EW) trials in the mid-seventies, we had a patient with MK. And in those days because of hospital ignorance she was mistreated and ended up with a very nasty corneal abscess. I never forgot the struggle they had to save the eye or the pain and suffering of the patient. (The case was only settled ten years ago). So we do not treat this subject lightly.

Bacterial Microbial Keratitis in a low Dk EW patient.

Is MK with High DK Soft Lenses Significantly Reduced?

The real question, the one we all need answered, is whether the risk of Microbial Keratitis is reduced with the new High Dk soft lenses?

The classic studies of Cheng, Schein, and their colleagues[10, 11] assess the incidence of MK with EW of Low Dk soft contact lenses at 1 in 500. We found double that rate in our prospective studies with 6 night Low Dk soft lens EW with 6 MK events in 2287 eye-years (number of eyes x number of years of wear) or 1 in around 380 eye-years [1].

Thus far neither the CCLRU/CRCERT (1000 eye-years) nor CCLR (500 eye-years) have had a case of Mk with High Dk soft contact lenses in our prospective 30 night CW studies (in Australia, Canada or India). Though this is promising it is as yet not statistically significant at the 0.05 level (p= 0.08).

There have however been reports of cases of MK occurring with silicone hydrogel lenses. We have been monitoring these reports closely, and there are, to our knowledge, a total of six: one in Italy, one in the US and four in Melbourne, Australia. It brings the number of MK cases reported to us to 6 in approximately 200,000 wearers.

If we speculate that there may be another 4 or so cases that we do not know about, it would mean 10 cases per 100,000 patient years or 1 per 10,000 patient years, compared with the currently accepted figure for Low Dk soft lens EW of 1 per 500 patient years[10,11]

We always knew that MK would occur with High Dk soft lenses. While products and practitioner advice are designed to be safe, unfortunately we know that not all our patients will be compliant all the time. We also do not know just how much additional protection eliminating hypoxia provides. Thus some patients will be at risk of infection, despite our best efforts. It is now a matter of determining the risk and rate of MK with High Dk soft lenses relative to Low Dk lenses. Whether these 6 cases are the tip of the iceberg or isolated and unusual events, we do not know.

The only way to resolve the issue is to conduct a properly controlled scientific study of the prevalence or incidence of MK with High Dk soft lens wear. This requires a very large patient sample to have worn lenses for at least a year. We are attempting to mount such a study with our national and international colleagues as a matter of some urgency.

The Future

Extended wear will continue to make an impact on the contact lens market as patients search for more convenient and safe forms of vision correction. It would be a great shame if the obvious corneal health of the 30 night HDkS continuous wearers as indicated by both the elimination of the signs of hypoxia and also by University of Texas corneal cell Pseudomonas adherence data[12] did not translate into far lower MK risk - especially as the modality gets the very solid thumbs up from successful wearers as a LASIK beater.

Researchers and practitioners will continue to monitor the results of extended wear in terms of patient safety. Accurate measures of the rates of adverse responses will be important in addressing practitioner fears and in ensuring the safety and efficacy of this new form of vision correction.

If there are many more unreported MKs it is definitely back to the drawing board, but the overwhelming satisfaction of successful 30N CW patients makes this quest well worthwhile.

Practitioners with Attitude (PWA)

The new silicone hydrogel materials bring the possibility of truly effective, safe, extended wear which fulfils both patient and practitioner expectations one step closer. What is needed in the real world to assess how well this new generation of contact lenses is performing is practitioners who are willing to review the results, listen to the experience of their colleagues and, if satisfied, try it for themselves and their patients - Practitioners With Attitude.

The most important thing is for practitioners to be well informed and to develop an attitude to silicone hydrogels as a way of fulfilling the needs and desires of our patients for convenient, effective continuous vision. Vision correction is a changing and challenging arena, and we owe it to our patients to deliver the best possible correction. Practitioners need to be willing to gain first hand experience, before making a decision about this new modality, as it will only be proven in the public arena.

References

1. CCLRU/CRCERT studies, 2000

2. Holden BA, Mertz GW, McNally JJ: Corneal swelling response to contact lenses worn under extended wear conditions. Invest Ophthalmol Vis Sci 24: 218-226, 1983

3. Holden BA, Mertz GW: Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci 25: 1161-1167, 1984

4. Fonn D, Du Toit R, Simpson TL, Vega JA, Situ P, Chalmers RL: Sympathetic swelling response of the control eye to soft lenses in the other eye. Invest Ophthalmol Vis Sci 40: 3116-3121, 1999

5. Covey M, Sweeney DF, Terry R, Sankaridurg PR, Holden BA: Hypoxic effects of high Dk soft contact lens wearers are negligible. Optom Vis Sci 78: 95-99, 2001

6. Keay L, Sweeney DF, Jalbert I, Slotnitsky C, Holden BA: Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis Sci 77: 582-585, 2000

7. Papas EB, Vajdic CM, Austen R, Holden BA: High oxygen transmissibility soft contact lenses do not induce limbal hyperaemia. Curr Eye Res 16: 942-948, 1997

8. Dumbleton K, Chalmers RL, Richter DB, Fonn DB: Vascular response to extended wear of hydrogel lenses with high and low oxygen permeability. Optom Vis Sci 78: 147-151, 2001

9. Dumbleton KA, Chalmers RL, Richter DB, Fonn D: Changes in myopic refractive error with nine months' extended wear of hydrogel lenses with high and low oxygen permeability. Optom Vis Sci 76: 845-849, 1999

10. Cheng KH, Leung SL, Hoekman HW, Beekhuis WH, Mulder PG, Geerards AJ, Kijlstra A: Incidence of contact-lens-associated microbial keratitis and its related morbidity. Lancet 354 (9174): 181-185, 1999

11. Schein OD, Glynn RJ, Poggio EC, Seddon JM, Kenyon KR (1989): The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses: A case-control study. New England J Medicine 321 (12): 773-778

12. Ren DH, Petroll WM, Jester JV, Ho-Fan J, Cavanagh HD: The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. CLAO J. 25 (2): 80-100, 1999