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									The History of Clinical Grade Poly Methyl
Methacrylate (PMMA CQ)
First published in the American Journal of Ophthalmology Vol 62 No 1 July 1966
under the title “Safety Requirements for Contact Lens Materials and their
Manipulation and Use” by J.M.J. Estevez, BSc FRIC API

As the last war was draw ing to a close Harold Ridley made the observation that
splinters f rom the transparent canopies of fighter planes were acceptable within
the eye. This was communicated to the manufacturers of the material which was
used to make these canopies, and an undertaking was given that material of this
quality would be made available to ophthalmologists. The material was
polymethyl methacrylate. Though Ridley’s main interest at the time was the
provision of artificial crystalline lenses the assumption was made that a grade of
poly methyl methacrylate proved suitable for intraocular surgery would be
suitable for prostheses such as contact lenses, tear ducts etc. Since the 1950’s
the clinical experience of poly methyl methacrylate has justif ied this assumption.

The grade of poly methyl methacrylate referred to was developed for the use of
fighter aircraft. As a plastic poly methyl methacrylate was new and production,
though forced ahead by the exigencies of war, was in an early stage of
development. Attempts had been made to control its qualit y and especially its
transparency, its strength and its resistance to heat. Between them these
requirements demanded a high degree of purity and a high degree of
polymerisation; that is the use of a monomer substantially free from impurities
and a polymer substantially free from monomeric methyl methacrylate.

Since the early forties poly methyl methacrylate has become one of the plastics of
major commercial importance, and w ith this has arisen a need for forms of the
plastic quite different from that of the sheet used in aircraft. Further during the
late forties and fifties the chemistry and technology of poly methyl methacrylate
have become better understood. Processes which were satisfact ory some twenty
years ago are no longer economic today and many materials which are much
more sophisticated, in the two senses of the word, than the original materials are
today freely available to commerce. None of these can be recommended as being
clinically safe; in the first place because properly conducted trials have not been
carried out, and in the second place because some of the development technically
desirable necessitated the use of agents of known toxicity or of doubtful safety.

The material made to the original formula which is still recommended for
ophthalmic work differs f rom the general run of poly methyl methacrylate in the
follow ing respects:-
1. It is made by the polymerisation of a methyl methacrylate monomer of the
highest attainable purity and is f ree from any additives. It is of interest to record
that this purity is higher today than twenty years ago, as a result of a better
understanding of the operation of distillation.
2. It is catalyzed by a trace of benzoyl peroxide.
3. It has a very low content of un-polymerised monomer.

The trace of benzoyl peroxide used to initiate the polymerisation reaction breaks
down to a number of other chemical entities some of w hich are free, but of
course in extremely low concentrations, and some of w hich are bound to the
polymer. 1 2 3 Benzoyl peroxide itself in this quantity and its breakdown products,
phenyl benzoate, benzoic acid, carbon dioxide etc. are harmless substances.
Benzoyl peroxide was used at much higher concentrations for many years as a
baking powder having bleaching properties.

It is considered essential for surgical applications that the methyl methacrylate
polymer be free of impurities, that any catalysts used have breakdown products
at least as harmless as those of benzoyl peroxide and that methyl methacrylate in
its monomeric form be no higher than 0.5%.

Restricting attention to sheet and block materials these are not desiderata for the
vast majority of markets for which poly methyl methacrylate is manufactured. For
example:-
1. Muc h poly methyl methacrylate becomes scrap and enters the trade of scrap
merchants. It can be converted to monomer by a simple heating operation and
the resulting monomer can be polymerised again to give sheet excellent for many
purposes. But reconstituted monomer always contains traces of impurities carried
over from the scrap, and it breaks dow n chemically in the process to the extent
that its odour is recognisably different from that of pure monomer.
2. Benzoyl peroxide is not now the only catalyst used in polymerisation. It
cannot, for example, be employed w ith many colouring agents. Other catalysts of
different behaviour are now general, and at least some of these are know n to
break down to products of high toxicity. An example in the literature is azo bis iso
butyronitrile 4 which has been widely advocated but which breaks down to the
highly toxic substance tetra methyl succinonitrile. Needless to say these toxic
products can occur in sheet made from monomer regenerated from scrap
polymerised originally with their aid.
3. Today most poly methyl methacrylate contains agents deliberately added in
the polymerisation reaction either to aid manufacture or to convey some
advantage on the resulting sheet. For examples methacrylic acid is sometimes
added to assist the dispersion of pigments or to provide an element of
crosslinking in the polymer, and some grades have phenone derivatives added to
them to confer some resistance to ultraviolet light or indeed to offer some degree
of opacity to ultraviolet light. Many of these agents are probably harmless, but
this has not been proved by clinical trial.
4. The manufacturer of sheet attempts to achieve as low a monomer
concentration as possible, and this for good technical reasons; but there are
processes for making sheet in w hich it is just not possible to control the content
of free monomer. As is well known methyl methacrylate is offensive to the eye;
hence all such processes are inadequate when ophthalmic surgery is the final
outlet, however satisfactory they may be for other outlets.
Poly methyl methacrylate is an article of commerc e in other forms than sheet and
block. Each offers some technical advantage but none complies with the
requirements of clinically proved safety, and so many more serious objections can
be raised. These are:
1. Rod. If the rod has been made from bloc k to the above specification no
objections can be raised. If, however, it has been moulded or extruded the
objections hereafter will apply.
2. Moulding and Extruding powder. Poly methyl methacrylate is a plastic which in
its pure form is not amenable to the modern economic techniques of mass
production. Both injection moulding and extrusion are prohibited to poly methyl
methacrylate because its viscosity in the molten state is too great. This viscosity
can be lowered by the addition of special agents or by a process whereby methyl
methacrylate is copolymerised with another monomer such as butyl acrylate or
ethyl acrylate.5 6    Various physiologically active          chemicals have       been
recommended, as additives to achieve properties desired in moulding or
extrusion. Amongst such additives are mercaptans 7 8 , thioglycollic acid and di-
isopropyl dixanthoge. This subject occurs frequently in patent literature9 1 0 1 1 .
Again one must object to the use of such materials in ophthalmic applications
because at best these additives are untrie d, and at worst because amongst those
used are some which carry a very real toxic hazard.
3. Dental Granules. Granules for dental prosthesis are of a degree of purity
commensurate with sheet material made especially for ophthalmic work, but they
do not lead to adequately transparent mouldings. It is possible to increase the
clarity of mouldings w ith monomeric methyl methacrylate. This is quite
unacceptable as the final content of monomer is too high. Furthermore most
dental granules in commerce are sold under proprietary names of formulations
kept secret. These formulations c onsist of small additions of special agents such
as glycol dimethacrylate to the poly methyl methacrylate granules. The
formulations are ha rmless enough for dentistry but could present unknown
hazards for ophthalmic surgery. The aim of all these additives is to produce a
hardermaterial than that provided by poly methyl methacrylate. It is perhaps
worth noting that the problem of finding what can be leached from a contact lens
into a human eye by experiments in the laboratory is almost, if not actually,
insuperable. In the first place there are analytic al difficulties. One is dealing with
organic materials of signif icance in fractions of a part per million, beyond the
most ref ined analytical techniques. In the second place it is difficult, if not
actually impossible, to reproduce tear fluid as an extractant. It is known from
work on attempts to produce an artif ic ial sweat fluid that very minor differences
in constitution - parts per million of a soluble protein for example - have a
remarkable effect on extraction results, To ease analytical difficulties one
attempts to concentrate results by working at elevated temperatures and at
exaggerated ratios of extractant to extractable, and then one finds that it is well
nigh impossible to interpret results. And overall there is the fact that extraction
works with polymers, even of the simplest kind, is far from straightforward and
involves phenomena, which are not at all understood at
the present time.
Thus one concludes that the only material which can be recommended with
complete confidence for the fabrication of lenses is sheet poly methyl
methacrylate specially manufactured for this purpose. But one must stress that
the problem of offering patient lenses free f rom hazard does not end here.
Hazards can be introduced in fabrication, packaging and use.

It is a property of the methyl methacrylate polymer to remain in a meta stable
equilibrium w ith its monomer dependent on temperature and pressure. Polymer
for lens making has about 0.5% monomer, and this is dissolved within the
polymer. If as a result of overheating which results in the conversion of polymer
to monomer, or of contact of with liquid monomer or monomer vapour the
polymer/monomer ratio is altered. The excess will diffuse out again when the
external environment changes. If, for example, polymer w ith excess monomer is
put in an oven or under vacuum the excess will diffuse out, but slowly. Likewise a
lens w ith excess monomer w ill slowly, perhaps over a period of weeks or months,
shed monomer to a patient’s eye. When poly methyl methacrylate is heated it will
decompose into its monomer methyl methacrylate, but also methyl methacrylate
when heated polymerises to poly methyl methacrylate. Which reaction takes
precedence over the other depends on the content-of monomer in the polymer,
the temperature and the general conditions. An equilibrium is established. If one
considers the temperatures employed in shaping and disregards those which
cause rapid de-polymerisation one can make the generalisation that for a polymer
of good initial quality heating favours de-polymerisation whereas cooling favour
polymerisation.

The temperature range recommended for forming poly methyl methacrylate is
140° to 150°. If these temperatures are adhered to and the sheet not taken
much above 150° in the heating operation and the operation of forming carried
out reasonably rapidly and that of cooling reasona bly slow ly, the original
equilibrium of polymer to monomer will not be significantly disturbed. Holding the
temperature of the sheet at 160°C could be dangerous. At temperatures higher
than this de-polymerisation will lead to blistering and w ill not therefore go
undetected. If the lens is made without heating by a grinding operation on a
lathe, except in the improbable circumstances of excessive frictional heat, the
monomer content of the sheet supplied originally w ill be left undisturbed. For
good quality sheet this is of course advantageous; but for sheet having .a slight
excess of monomer, this is not so. In a shaping operation carefully and correctly
carried out such a sheet would have its monomer content diminished, and this
could bring what was marginally unacceptable to an acceptable state.

The cementing of two or more elements to make a lens is always attended by
some risk and should be avoided if at all possible especially if either part has
undergone a shaping process at elevated temperature. 1 2 Of the cements used for
joining two pieces of poly methyl methacrylate the least dangerous is methyl
methacrylate itself. The edges of the piec es when treated with this agent soften,
and when the pieces are brought together the material of each forms a
consolidated whole w ith the other; but the excess of monomer diffuses
throughout the mass of the polymer. It can of course be polymerised or
evaporated. Both are slow operations. Polymerisation would require a
temperature above that at which a lens shaped w hen hot would begin to revert to
the original f lat sheet from w hich it was made. A temperature of about 120°C
would be the minimu m for even slow polymerisation and one of 80°C about the
maximum for safety from reversion to flat sheet. If no part has been heat treated
one would still put a maximu m at 80°C as above this strain introduced by
machining could cause the same kind of reversion to some degree. He nce to
restore the original equilibrium concentration one must rely on evaporation and
not polymerisation but evaporation at 80°C is not at all quick.

It could be hastened by a strong draught (at this temperature) or better by
vacuum; but even so the time would be prolonged, and 24 hours could be
insuff icient. Of course one must insist on all c ementing being carried out with the
absolute minimum of cement. Methyl methacrylate monomer for this purpose is
best made more viscous by dissolving in it some chips or swarf of the polyme r.
This effectively dilutes the monomer, but even so one should aim at us ing the
barest minimum. Cements containing accelerators must not be used.

In all work in which moulded sheet poly methyl methacrylate - such as a
thermally formed lens or the haptic portion of a lens - is subjected to elevated
temperatures as during an annealing process the tendency of the moulding to
revert back to the flat sheet from which it was formed must also be recognised. It
is this tendency that puts an upper limit to the temperature possible. When this
operation is carried out the moulding should be constraine d as far as possible,
and a jig such as the original forming tool used for this purpose.

The method of sterilising lenses by leaving them in dilute caustic soda assists any
previous attempts to reduce the content of methyl methacrylate monomer.
Though this process does help, its action is too slow to be relied on as a method
of achieving this result. Were the lenses to be left in the solution for a day or so
the help could be signif icant. Methyl methacrylate vapour is used by some
operators to give a f inal polished appearance to work that has traces of opacity
from grinding. Such a technique cannot be regarded as permissible for the
making of contact lenses. It would take many days of careful heating to bring
down the monomer content to an acceptable level.

Even more reprehensible is the practice of dipping lenses in the monomer to
soften them so that minor adjust ments may be made. Not only is there a risk of
surfaces being impaired by very fine crazing, but the monomer content will be too
high for it to be reduced by evaporation. It is unlikely that such a content could
be reduced to acceptable proportions in under 7 days vacuum heating at 80°C,
and it is possible that lenses so ill- made as to require an adjust ment would not
withstand a temperature of 80°C. This would necessitate something like double
the time at 70°C, that is 14 days or more. The idea that excess monomer can be
removed by blowing it away with compressed air until the odour has gone is quite
ludicrous.

Attention should also be drawn to the fact that poly methyl methacrylate can
absorb other solvents and discharge these slow ly into the eye. Cosmetic fluids
such as perfume spilled onto a contact lens or falling on a lens from a scent-spray
could, if not immediate wiped off, be absorbed in a matter of hours and spread to
the eye in a matter of hours or days. Hairsprays have been reported as harmf ul in
this connection. Poly methyl methacrylate can also absorb organic fluids from
packaging materials, with again a fair rapidity of absorption followed by a slow
discharge. Plasticiser from f oamed PVC or foam cellulose acetate used in a
cushioning or from a varnish can lead to this danger, as has been reported.

It must also be acknow ledged that if the surface of a lens were to be softened by
a solvent - the vapour from nail varnish could be a cause - in a dusty atmosphere
small particles of solid matter could be trapped in the surface of the plastic which
would have an abrasive effect thereafter.

This property of poly methyl methacrylate towards organic fluids should be
acknowledged in the careful selection of packaging materials and in advising
patients to be ultra-cautious in keeping their lenses away from domestic and
cosmetic fluids, and their vapours.

The subject of coloured contact lenses raises special problems. It is a simple
matter to produce coloured poly methyl methacrylate sheet by using dyes soluble
in esters, but unfortunately all such dyes fade to an uncontrollable degree w hen
benzoyl peroxide is used as the catalyst to initiate polymerisation. Again if the
sheet is “dyed” after polymerisation, the “dyes” adhere only partially to the
plastic and are rapidly eroded away. Furthermore none of these dyes is entirely
acceptable on physiological consideration, nor are the materials used to fix them.

The alternative is to use inert pigments such as carbon black, ultramarine, iron
oxide, chromium oxide and titanium dioxide. All such materials are inert in
themselves and are immobile in the polymer, but being pigments they raise the
problem of opacity. Normally a sheet of poly methyl methacrylate pigmented with
such materials is opaque. A certain translucency can be obtained w hen the
pigments are used sparingly and when fully dispersed throughout the mass; and
in sections of 0.8 mm downwards this translucency can be taken as a
transparency. Full dispersion remains however a problem, since agents such as
methacrylic acid which at the 2% level aid dispersion are quite unacceptable in
material whe re purity is of prime importance. However poly methyl methacrylate
sheet pigmented in this way and conforming to the conditions of purity mentioned
earlier in this paper, has been made experimentally, and is being developed for
commercial production. Only such materials can be expected to be free from
hazard. Objection has been taken to the content of methacrylic acid as an
impurity in the poly methyl methacrylate used for making lenses, and a
specification laid dow n requiring a maximu m of 10 p.p.m. not to be exceeded in
the monomer used for polymerisation, It is felt that this is irrelevant to the
problems of lenses. In the first place this happens to be the order of purity of
commercially available monomer, at least that sold by the bigger companies; so
the majority of lenses conform to this in any case. Nevertheless one would have
thought that a very much higher concentration than this would be harmless.

Methacrylic acid is itself a polymerisable monomer, and when present in methyl
methacrylate monomer in a reaction designed to polymerise the latter will
copoly merise w ith the major constituent so as to lose its identity completely. One
would expect this to be true of a concentration many times the 10 ppm
mentioned. It is highly improbable that such a copolymer could be broken down
to yield the free acid at the temperature and pH of tear fluid.

Excessive quantities of methacrylic acid could result from intentional addition, but
this seems pointless as no useful purpose would be served and it would raise
costs. Again excessive quantities of methacrylic acid could result from making
sheet from regenerated monomer obtained from heating scrap, but this would be
only one of many objections to the use of scrap and by no means the most
serious.


1
  Flory, “Principles of Polymer Chemistry”, New York, (1953)9 P-106
2
  Walling, “Free radicals in solution” New York, (1957), P-76 and p474 et seq
3
  Tobolsky and Mesrobian, “Organic Peroxides”, New York (1954), p72 et seq
4
  Schildknecht, “Vinyls and related polymers” New York (1952), p199
5
  Ibid, p200
6
  Riddle, “Monomeric Acrylic Esters”, New York, (1954), p67
7
  Ibid, p56
8
    Cohen and Sparrow, J.Poly.Sci. 3 p693 (1948)
9
  U.S. 2,396,997 (1946) Goodrich Co
10
   U.S. 2,450,000 (1948) Du Pont
11
   U.S. 2,462,895 (1949) Du Pont
12
   Estevez & Powell “Manipulation of Thermoplast ic Sheet, Rod and Tube”,
London 1960, Chap 4

								
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