Journal of the British Contact Lens Association, Vol. 15, No. 4, pp 181-194, 1992 © 1992 British Contact Lens Association Printed in Great Britain

SESSION I: BACK TO THE FUTURE

Panel: Brian Holden, Brian Tighe, Graeme Young, and John de Brabander

Discussion Atkins: In the 2-week disposable and 6-month replacement lens study, which materials were used?

Holden: In the eye in which the lens was replaced every 2 weeks an Acuvue lens was used. In the eye that was not replaced in the 6-month study the material was an experi- mental one which we cannot disclose at this stage because it is not on the market.

Question: Is the infection rate higher or lower with disposable lenses?

Holden: This is a pretty tough question. It does appear from all the data that have been collected so far and from all the studies with which I am familiar that the serious infection rate may be less with disposable than with conventional lenses, although good data are not available yet.

What we do know is that ulcers found with disposable lenses are more peripheral than those found with conven- tional extended-wear lenses, which are more central. As yet, though, their etiology is not determined.

A number of studies that are about to be published also indicate that the infection rate may be less with disposable lenses, but the figures are woolly at this stage and it is diffi- cult to comment further at present.

Question: Could Professor Holden comment on Efron and Veys' assertion that edge defects with disposable lenses con- tribute to serious infections.

Holden: The data that Nathan and Jane Veys have collected on disposable lenses indicate that there are edge imperfec- tions or edge defects on a number of lenses; 75% was the figure with the Acuvue lenses. We have looked at edge defects on disposable lenses and found that at 17.5 times mag- nification if we look very carefully we can find something on 62% of lenses. In our estimate, defects would apply to 10-12% of those lenses. Their study shows that after 1 week of extended wear there is 0.3 unit extra of conjunctival staining, and 0.7 unit extra of corneal staining, and 1.6 microcysts extra. The 1.6 microcysts extra is interesting, but irrelevant, because after people wear the lenses for a couple of months they have between 30-50 microcysts anyway. The extra staining is very slight, and the suggestion that this could make a major difference to serious infections is far from the mark; there is no evidence for it at all. However, the useful point that they make is that, if possible, lenses should have no extra bits of flashing or extra material on the edge.

Cameron: Has Professor Tighe studied viscosity effects of artificial tear solutions? Why do patients find some signifi- cantly better than others?

Tighe: Ian Bright has studied extensively the properties of these solutions.

When it is said that patients find some solutions better than others, let me refer to some work by Nathan Efron. He used saline solution and some artificial tear solutions and reported that the difference between these, on the basis of a statistical analysis, was very little. If true, an explanation is that the

surfactants in the eye move very rapidly and, during a blink, water or saline instilled into the eye will have a very similar surface tension to that of tears, and in fact the tonicity will rise very quickly; which is seen in the tear drainage graphs. If there is a difference in effect, and I do not know this to be the case, I would say that the artificial tears that we have looked at differ by a factor of about three in their viscosity. It may be that that has some clinical effect; I can only say I have not seen any factual data to that extent. But they do differ by that amount.

Cox: Does rubbing lenses with the solution improve wetta- bility?

Tighe: Yes; it improves the wettability of the lens by that solu- tion. It is exactly the same as having a windscreen wiper. If we mechanically establish a layer, the ease with which the layer is established and the ease with which it is broken up are not the same. It is much more difficult to form a layer on a lens than to break it up. Once a layer is established on a lens, especially if it is a viscous solution, the layer is retained. It is the difference between the so-called advancing and receding contact angle.

Holden: When lenses are conditioned, how long does that conditioning last or is it just to break the lens into the tears?

Tighe: K a rigid gas permeable (RGP) lens has been stored dry, essentially we convert COOH groups on the surface into COO- cations, at a pH of around 7.4; this conditioning will last as long as the lenses are retained in a solution of similar pH. Also, all RGP lenses absorb some water, especially in the surface layers, and so the effect will remain as long as the lens is not dehydrated again.

Essentially, it is a matter of maintaining the lens in an aqueous environment or at a moderately high relative humidity.

Holden: With some of the fluorosiloxanes we have noticed that wettability in the eye takes days to improve.

Tighe: But that difference may not necessarily be due to the use of a different material. It could be due to absorption of biochemical species from the eye onto and into the surface layer of the lens. This is a quite different thing from the simple wetting effect. It is the absorption of molecules that are, in themselves, large and have a different chemistry to the surface of the lens. This is nature making the surface biomimetic.

If a poor synthetic material is put in contact with blood, then blood (just as an oyster coats grit) will cause a biological layer to be laid down on the surface of that polymer; that layer is more akin to blood. In technical terms this lowers the inter- facial tension, and this happens in the eye.

Holden: Are they mucins or surfactants?

Tighe: They are certainly not mucins. Mucin is very poorly adhesive to any synthetic surface and, indeed, to the cornea. It absorbs well onto intestinal mucosal surfaces, but not to the cornea.

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Certainly there are lipids, which are really a mix of polar and non-polar groups. It is only cholesterol that is a very non- polar molecule.

But a mixture of lipids and proteins is present.

Question: Looking at contact angle measurements, all the in vitro techniques seem to be somewhat irrelevant because of the effect of tears on surfaces. How important are in vitro techniques in assessing or predicting in vivo behaviour of the material?

Tighe: The in vitro techniques are important for two reasons. First, when one is designing a solution how does one know what properties it should have? If there is a range of solutions and one can see differences in clinical effects, it is only by making in vitro measurements that one is able to correlate a physical measurement with a clinical effect.

However, in vitro measurements are not in any sense good predictors of what happens in a biological situation. This is true with any device. We cannot tell in absolute terms and in the absence of any clinical correlation between groups of materials that X does Y, Y does Z, Z does A - we cannot pre- dict ab initio from in vitro measurements what the behaviour in the eye will be.

So it is absolutely right to say that in vitro measurements cannot be good predictors on their own. They can only be useful in correlating clinical behaviour.

In many cases, the in vitro techniques are so far removed from the actual physical behaviour in the eye or in any other body site that to use them is a compromise. It is simply that they provide the best physical data that we can obtain. All I would say is that this is better than having no data.

Bashawri: Is there any long-term effect on the cornea or con- tact lenses of wetting and conditioning solutions?

Tighe: I have no idea. As far as I know no study has been done that would indicate whether this is so or not.

Comstock: The push-up test optimal value was reported as 60%; 60% of what? I do not understand the scale:

Young: I am sorry I did not have the time to go into all of these in depth.

The scale is from 0-100, where 50% is optimum, 100% is so fight that we cannot move the lens, and 0% is extremely loose. It is a technique borrowed from the CCLRU.

In the context of our study, the absolute values are not too important. What is important is that we were able to show that the test is highly predictive.

Several studies have shown that, as a test, it is very repeat- able between investigators and correlates very well with the mechanics of an individual lens.

Comstock: With thin hydrogel lenses can visual acuity be used to indicate whether a lens is too tight?

rather than any experimental proof.

Stevenson: One of Graeme Young's early slides showed more of a tightness-comfort relationship with high water content (HWC) lenses than with low water content (LWC) lenses. Could it be because they were not allowed to settle for a suffi- cient time. I personally wait for 3-4 hours, because HWC lenses take some time to adjust to the eye.

Young: It was comfort that stood out on that slide from LWC and medium water content (MWC) lenses. For those studies with HWC lenses, we allowed at least 30 minutes, and nor- really 45 minutes, which is ample.

Work done by Brian Tighe has shown that with, for instance, Permaflex, 10 minutes is as much as is needed before the lens settles down, at least in terms of movement, and various other groups have shown that 10 minutes is adequate for a lens to equilibrate in terms of dehydration and SO o n .

What does sometimes happen is that the lens dehydrates, settles, reaches an equilibrium, and then, may be because of environmental factors or tear film, by the end of the day the lens shows a totally different fit. This is not so much lens- related as patient-related.

This would be established at the after-care visit; from a pragmatic point of view, 10 minutes is quite adequate for that initial fit.

Scanlon: A lens that is moving satisfactorily might become tighter over longer periods of time.

Young: The point that I was making, rather flippantly, was that if the lens is extremely tight after 20 seconds, it is not likely to loosen. Thepoint of the question is that if a lens is reasonably well fitting or loose fitting, is it possible that it can change over a period of time? Yes, certainly during the first 5 or 10 minutes it can.

Examine whether the lens is grossly tight, and if it is, leave it for the full !0 minutes and then assess it again.

Spicer: Graeme Young does not define his criteria for deciding whether a lens is a good fit or a poor fit. What his study shows is surely only an analysis of the criteria he already applies.

Holden: There is no objective criterion that this is good because the person is happy, or satisfied?

Young: We used the best criteria we could, and that was the investigators' feeling as to whether they would be happy to dispense the lens for a week at a time.

We did try to correlate between investigators so that all the investigators were using the same criteria, albeit subjective. But really the above was the best that we could do given the circumstances. I cannot think of a better or more realistic way of doing it.

Young: There are obviously several things that were not cov- ered by the evaluation. What I did was to take those which are most commonly used to assess soft lens fit. Obviously, there is a whole list of variables that I did not look at, such as overkeratometry and the spring-back test, so I am hesitant to comment on any other test that has not been validated experi- mentally.

I did show that before drawing any firm conclusions, a little bit of experimental work can be very useful.

I leave further discussion to Ian Davies, who is to cover the topic in a later session.

Holden: The criterion is investigator happiness?

Young: That is a good summary.

Amey: A useful guide to soft lens fit is the quality of the refinoscopic refex. Any comment?

Young: I will happily pass on that one.

Holden: Both retinoscopy and fluctuation in vision with thin- centre low water content lenses can indicate a bad fit.

Holden: With thin soft lenses, is visual acuity a guide or not?

Young: I must pass on that, as I only have anecdotal feelings

Question: What about the push-up test? Does that induce reflex tearing, possibly rendering the fit inaccurate?

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Young: No.

Warren: If high Dk materials are used, should planned replacement be considered to avoid lens spoilafion, scratches, and deposition? If so, what frequency is required?

de Brabander: We followed most of our patients for about a year, after which period we were still quite happy with the quality of the lens. As an estimate we should replace the lenses every 2 years and tell the patient beforehand. Then we have a very simple, safe system.

There is no need to state that high Dk materials need to be replaced every year - it is not the case with modern well-man- ufactured lenses.

Holden: What care systems do you use?

de Brabander: We always use the combination of an all-in-one solution which contains a chemical cleaner and an abrasive cleaner - always both. The storage solution contains a chem- ical cleaner and, as an extra, we have a mechanical cleaner. This is the optimal system.

Patients can use the abrasive cleaner every day.

Holden: What do you use for lipid deposits?

de Brabander: The abrasive works.

Question: In fitting high Dk lenses, e.g. Quantum I or Quantum II, is a Quantum II trial set needed to fit Quantum II lenses?

de Brabander: It depends very much on the quality of the manufacture. If it is of a high enough quality, then even a PMMA trial set can be used. We change materials without extra trial fit and this works very well. But a reproducible lens is needed.

Question: Would Professor Holden elaborate on the high inci- dence of eye infections implied in the UK for daily wear dis- posables?

Holden: There was a paper published by Nathan Efron and some colleagues which reported that three of 120 disposable wearers had Pseudomonas ulcers; from this they projected an annualised incidence of 4.3% serious infections with daily wear disposables. The comment was made that people were taking lenses out, throwing them into containers with chlo- rine tablets and not rubbing and rinsing. The incidence is unusual. I do not think there are any other reports with such high levels of suggested incidence of serious infections with daily wear disposable lenses.

I have heard recently of a very high incidence of Acanthamoeba infections. Coming out of Moorfields, someone mentioned that they had 55 cases of Acanthamoeba infections, which is extraordinary.

The suggestion is that the care systems that are available are not doing the job, or are not being used properly in prac- tice; it is probably a little bit of each.

Question: Are care systems laboratory based rather than relating to actual patient wear and compliance?

Holden: The approval of care systems in many countries has vacillated between testing a single solution to see if it is capable of killing bacteria and testing a system, which includes cleaning, rubbing, and rinsing. The UK has gone for testing individual solutions, which means that some of the solutions cannot get on to the marketplace, although they seem to be fairly good at controlling care-related infections. This, however, is a matter for the Department of Health.

Polse: Everyone agrees that there are infections with contact lenses and we can argue over the incidence and prevalence. But what is perhaps interesting is that, considering the amount of deposition of potentially pathogenic bacteria on contact lenses and on hands, more people are not becoming infected.

Of interest is the hypothesis that Brian Holden suggested in his talk, based on some research now being done at Harvard, where hypoxia might be one of the driving factors that is altering infection rates. Would he feel comfortable to explore here what might be going wrong? Obviously, some- thing is going wrong in a very small percentage of people. If we take 100 people, they are all being exposed to very similar environments; we can try to rule in compliance, lens coating, etc., but when we factor all these out, there is still something very special that is happening to certain people at certain times which is allowing them to become infected.

I wonder if Professor Holden has thought about this hypothesis more and would want to shed any light on it.

Holden: It is an interesting question. We are exposed to numerous pathogenic organisms in our daily lives. Pseudo- monas is very common in water and so forth, and we do not normally become infected because we have these care systems.

One simple example might be, for instance, that fibronectin is a compound that preferentially adsorbs gram-positive organisms and, as it were, rejects gram-negative ones. We know that there are fibronectins on the surface of the eye, and we could postulate that if the cells are not functioning prop- erly, then they are not synthesing things that are part of the natural defence mechanism. One can continue along as one does with, say, disposable lenses, without peripheral corneal ulcers occurring for 2-3 years, and then the combination of circumstances becomes too much for the system, or the system defence drops, or the person becomes debilitated (we have noticed a relationship between when people suffer acute red eyes and when they become ill with influenza and so forth). So the system defence drops, there is much bacteria present, which can become stuck on the cornea.

Such a sequence is something that is very difficult to guard against unless we remove the basic compromise. The real question is, ff we restore full levels of oxygen with a soft con- tact lens, if we had a silicon elastomer that worked and a healthy functioning epithelium, would the tear exchange be enough under the soft lens for it to be perfectly safe? I do not think that question has been answered.

But I would suggest the data are very strong that high Dk RGP lenses are a safe option.

Polse: I agree with that last statement. The data strongly sug- gest that high Dk materials are safer, which again adds evi- dence to the suggestion that hypoxia must be altering the cellular basis in the immunological response, and there must be a basic cellular response for some people when they are subjected to this hypoxia that lowers their immune system. The bacteria are already present, the epithelial defect is pre- sent, and infection takes place.

Where the cutting edge of research has to go is that we now have to be able to identify those people in whom cellular basis is at risk for altering its immunological response. Those are the people who may be infectious.

I do not know what the answer is, but that is what we have to start looking at; this is what Professor Holden is doing at the CCLRU, and others are doing elsewhere.

To me, and this may be a naive approach, we should examine the coatings on lenses at this point in time. Disinfecting systems are important, but still not the central driving issue. We now have to understand this next cellular level if we are really to conquer disinfection; at the same time we must drive towards very high Dk materials. But until we have these, may be we can identify risk patients through a

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better understanding of the immunological response system.

Woods: I have been trying to fit quite a few high Dk gas per- meable lenses over the past few years. When I have patients in whom the lens will not wet in the eye, I have been sending the lenses back to the manufacturers and blaming them.

What I found interesting was the comment that we should tell the patients to take those lenses away to let them settle down. How long should we leave those lenses in the eye to see if wettability is likely to improve? Is that for all gas perme- able lenses, regardless of Dk, and at what level of Dk should we be thinking of doing that?

Holden: There are many, many things that affect the wetta- bility of RGP lenses: how well they were manufactured, how well they were cleaned after manufacturing, whether all the grease and the oil was removed, and so on.

When they come into the practice they probably need to be soaked for 48 hours to obtain full water content into the lenses, and then they are put into the eye; if they are not wet- ring too well, over a period of time they will wet.

In terms of how long, I guess a couple of days usually shows adequate improvement to be able to judge. However, if something is badly wetting, it is not on anyway.

de Brabander: We have the same experience. It takes 1-3 days for a lens to become properly wet, and I do not think this depends very much on the Dk.

Tighe: This is a very rational period of time, which is explained by all the events we discussed earlier.

It is not really Dk-related, except to the extent that Dk inevitably changes the hydrophobicity of the material.

Holden: In some cases manufacturers are now surface- treating lenses with plasma. Is that to clean the surface, or does it create chemical changes that help?

Tighe: It does create chemical changes. But any surface that is plasma-treated will decay. Its surface activity will change. Really, the extent to which this is a benefit will depend upon the age of the lens. Generally, if there is silicon in the lens, it has been shown that the silicon methyl groups present in all lenses are changed to SiO2 on the surface.

Certainly, plasma treatment makes a lens more wettable. It will also clean the surface, but this is a secondary consideration.

Question: A quick corollary to what has been said. Should the patient not use their surfactant cleaner in the first 3-4 days of wearing their gas permeable lenses?

surfactant?

Question: Because wetting improves on the basis of absorp- tion of certain tear constituents, and maybe the cleaner removes those and is acting in a negative fashion.

Holden: Very subtle.

Question: Or does the cleaner not take away these beneficial tear constituents?

Tighe: Imagine cooking sausages in a flying pan and then leaving the pan overnight and coming next morning with cold water and some washing up liquid; one would never remove all that grease from the surface.

Quantitatively, the surfactant cleaners only remove at best 60-70% of what is on and in the surface layers. It is essential to use the surfactant cleaner, but it will not remove all the material. It will not remove the material that is strongly bound to the lens, and that will be beneficial in conditioning the lens - to use the terms that were used earlier.

Question: Would it not be better to use a separate wetting solution of higher viscosity, rather than all-in-one wetting-and- soaking solutions?

de Brabander: Why should we?

Holden: Is it better to use a specialised wetting solution?

de Brabander: I do not think so: no.

Tighe: They differ by quite a bit. I really do not think there is any case for choosing a single-purpose rather than a multi- purpose solution. The surface tensions and wetting character- istics are not very different between all-in-one solutions and single-purpose solutions.

The question of viscosity is more a matter of personal pref- erence. I do not think there is any case for making a rule based on this physical measurement.

Bosch: We were discussing the replacement rate of contact lenses. We know that with soft contact lenses the ideal rate of replacement is between half a year and perhaps a week. But now we are in the process of replacing RGP lenses.

Surely it is our job as contact lens practitioners to prevent problems. We are talking about contact lens consumers and we should not wait for problems to appear, but should prevent this. In this light, annual replacement would be preferable to polishing and cleaning lenses, because cleaning and polishing really can screw up lenses.

Holden: Not in my estimation. Why would one not use a de Brabander: I agree; if one can afford it.

SESSION II: CLINICAL MANAGEMENT AND VISION

Panel: Joseph Molinari, Timothy Comstock, Neil Cox, and Ian Davies

Discuss ion Mitchell: 'Experimental' contact lens research seems to have manufacturer bias. What is the best way to receive adequate funding for independent experimental contact lens research without running into this manufacturer bias?

Molinari: In private practice, one way is to persuade associa- tions, such as the British Contact Lens Association (BCLA) to give a grant, and then there is no bias to a manufacturer. The

Dallos Award is available and there are several associations that have monies available to do research projects. We have used Dallos money to study contact lenses in underwater environments.

In the US, the federal government spends much money on esoteric studies. The American Optometric Association and the Academy of Optometry have put together a book that shows where to go to obtain these monies.

There is money around.

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