The transparency of the cornea is subject to a very delicate balance and there are many disorders (infectious, inflammatory, mechanical, toxic or dystrophic) that may provoke a loss of such transparency.
Among the dystrophic-type causes, we find keratoconus, which provokes a progressive bending outward at the center of the cornea, in this way forming a cone-shaped cornea and, naturally, causing a thinning of the corneal tissue.
This anomalous curvature induces image distortion and a confused vision from both near and far. But what are the causes of keratoconus? This is a question having different answers but, as of today, no sure one.
The Anglo-Saxon authors insist on an important component, continuous rubbing of the eyes, which would weaken the structure, provoking its initial and progressive wearing out. Or there is talk of a “familial” type alteration: it is not rare to see siblings, often twins, with the same disorder or in any case to find it in the same family, although within a wider kinship context.
Stroma “erosion” is also thought to be a possible cause, induced by an unknown mechanism that provokes a structural weakening of the crossed layers of cornea collagen. The reality is different, however. It is not a matter of erosion but of a “thinning” of the collagen layers (like elastic that, inert, has a certain thickness, but if strained, this is diminished almost directly in proportion to the length it is stretched by). So these layers in increasing their length undergo a thickness reduction and proportionally the cornea, whose surface is proportionally increased, is bent outwards.
Thus the corneal curvature radius increases because the corneal surface is augmented.
Very probably, the initial pathogenetic mechanism, which we may call factor “L” (so far unknown), creates a weakening situation in the stroma collagen fibrils, which have a helical shape (thus lengthening the helicoid). This relaxation, under the effect of the intraocular pressure that presses outwards, causes the “hunching” (or “wear”) of the cornea that, proportionally, undergoes a decrease in thickness.
Once begun, such wearing is then aided, as well as by the intraocular pressure, by the palpebral pressures too. As far as the former is concerned, depending on the fluid dynamics, this pressure would have to equally press toward the inside of a cavity, but this is not the case here, where we have elastic tissue and a variable thickness.
The latter mechanism, little considered so far, is the palpebral pressure, nearly exclusively from the upper eyelid: and that is why nearly all the keratoconus cases are inferior. This pressure acts on the cone, modifying the dioptric power of the cornea by several astigmatic diopters.
Suffice to observe, with the corneal topographer (an instrument for corneal curvature changes), an eye of a patient in supine position and with a blepharostat (palpebral retractor) applied. Both the total quota of the height variation from a medial reference point, and the spatial variation on the surface are checked. At the time of removing the blepharostat and leaving the eyelid to act on the keratoconus-affected eye, we are able to notice the curvature radius changes due to the pressure of this eyelid, expressed as an appreciable number of astigmatic diopters.
There is also a contrary testing for the concept just enunciated. There are in fact some rare cases of superior-type keratoconus, where one notes the wearing in the high part of the eye. In this case the keratoconus is nearly always of the “worn out” type, i.e. hardly ever having a progressive evolution because the pressure from the superior eyelids nearly always effectively exercises a containing effect on the ectasia.
Therefore there is an internal mechanism, intraocular pressure, and an external mechanism, superior palpebral pressure, and in certain cases, when the patient forcefully tries to focus on images thus deformed by the cone’s asymmetry, the pressure exercised by the inferior eyelid is added. This is why the patient tries to “pinch” the cornea using the eyelids like the two jaws of a pair of pincers, with the obvious consequence of greater pressure on the already diseased tissue and leading to a greater extroversion and thence to a worsening of the keratoconus.
Such a mechanism is similar to rubbing effects. It is clear however that these mechanisms succeed in worsening the damage, only because they are dealing with tissue that, for causes still not etiopathogenetically clear, presents itself with a “relaxed collagen” structure that constitutes the fundamental substance of the corneal stroma. The keratoconus is therefore the result of a “collagen disorder”.

Various techniques for treating keratoconus
We shall now examine the various procedures adopted by ophthalmologists to deal with the keratoconus problem. For many years contact lenses have certainly represented the only possibility for correcting the irregular surfaces caused by keratoconus, not otherwise correctable with any sort of spectacles. However, contact lenses act by damaging the eye, for three good reasons:
1) already in healthy eyes, it is common experience to notice how the use (or more often the misuse) of these prostheses involve a weakening of the eye that is demonstrated with reactive modifications in the production of the normal lachrymal film.
This is altered in its lipidic and proteidic layers, increasing in thickness in order to oppose these “foreign bodies”, thence creating a thicker cushion to reduce the friction.
On the other hand the contact lens misuse is due to the state of the keratoconus patient’s great need, who can only succeed in having acceptable vision by using the lenses. Our refractive surgery experience teaches us that: even for patients not affected by keratoconus, in wearers of corneal lenses, even if disused for many years, the trophism is no longer fully recovered with consequent infra-operative denudations that are unknown in eyes that have never worn contact lenses.
2) 70% of the oxygen supply to the “normal” cornea originates from the external environment and 30% from the intraocular liquids. The attempt by contact lenses producers is clearly to seek to promote in every way the “gas permeability” of the various lens types.
But it is an attempt that is only partially useful and true, because it is known that “synthetic tissues” are unable to absorb oxygen from the surroundings in an adequate manner, never mind being able to transmit it to the ocular surface.
In fact so-called “active transport” of oxygen is so far only possible for living biological tissue. Furthermore, the international literature provides us with a lot of data on the loss of endothelial cells caused from the use and above all misuse of corneal lenses. Above all, the lenses cover precisely the sickest part of the eye, i.e. the infero nasal-temporal part. Thus the mechanism of correct oxygenation is disregarded, aggravating the disorder still further.
3) The mechanism whereby the lens rests on the corneal surface exercises a further negative pressure that can be summed up by the “law of vectors” to the intraocular pressure that presses the cone outwards, acting like a mini suction pump on the cone’s apex. We could continue speaking about the mechanical-type application errors, how the lenses that touch the corneal apex provoke alterations that then give rise to semi-perennial scars known as “leucomas”, but we think that the picture on contact lenses is exhaustive for revealing the real harmfulness of this presumed remedy for keratoconus. Then, for some ophthalmologists and therefore for their patients, the conviction is still rooted according to which the only surgical means for defeating keratoconus is corneal transplantation.
Let’s look instead at why it should be avoided:
1) the first (and most determinant) reason: corneal transplantation has a mean duration time of 10 years (S.I.TRA.C. Convention, 18-19 February 2000). Imagine what such a short expectancy means for a young person. And those affected by keratoconus are nearly always young;
2) from the practical point of view, only whoever is on the waiting list for a cornea knows how difficult it is to find one;
3) let us not forget that is it is always a matter of transplanting tissue, with all the risks of rejection that it involves.
It is not possible, in fact, to guarantee its taking root in 100% of cases and, in the unfortunate case of rejection vascularization (present in 5-10% of cases, as established by Prof. Bisantis of the ophthalmologic clinic at the university of Padua), another transplantation would be impossible and the eye would be irremediably lost. Moreover, corneal transplantation, even if successfully carried out, regularly leads (with the current technological conditions that Italian and European health facilities generally have available) to a more or less high degree of astigmatism. We have sometimes seen operated patients with astigmatisms even of 8-12 and more diopters.
A situation even worse than what a patient experiences with his/her keratoconus. The optical correction of such astigmatic ametropia becomes extremely difficult or even impossible, even with the most sophisticated technology.
One has to then carefully inform the patient and think about the use of corneal transplantation only in those rare cases of acute keratoconus: thus where the cornea is already spontaneously pierced and transplantation is no longer postpone-able.
Or else in those cases of ample central corneal opacity, thick and irreversible (true leucomas), such as to jeopardize the patient’s visual capacity (and where it is not possible to clear up these opacities with appropriate eutrophicating therapies [that we have worked on]). It should be added that, precisely regarding the temporal precariousness of the graft, it would be necessary to advise against “risky behavior” like the use (and misuse) of contact lenses and surgical techniques that would accelerate the evolution of the disorder toward transplantation.
And on the contrary, then, to practice right from the first symptoms (i.e. from when the patient no longer presents with a Visus of 10/10 dispositions, but simply of 9/10) “asymmetric radial keratotomy”.
With its micro and mini incisions, proportionally limited to the precocity of the disorder, this will offer a way out from the “tunnel” that leads to the corneal graft, with a success rate that no other surgical technical can so far achieve.
Indeed, such surgery (used by my team and other surgeons in Italy and throughout the world) should not only be considered as today’s best solution for keratoconus, but also, from now on, as a prophylaxis for the evolution of keratoconus.
Given my role as a pioneer in the field of refractive microsurgery and with an experience of thousands of refractive operations since 1980, I have been able to conceive (already since 1985) of this simple operation to resolve definitively (in 95% of cases) the keratoconus problems of types I, II and some selected cases of type III. This operation has proved itself, with the outcomes achieved over 15 years, able to reduce at least by 95% the need for corneal transplantations for keratoconus in the world.

Asymmetric radial keratotomy
The technique that I conceived, called “asymmetric radial keratotomy” derives from the one used for the correction of myopia, first by Sato (1955) and then my mentor Fyodorov (1975).
With this technique some radial incisions are made on all the paracentral part of the cornea through 360o. In asymmetric radial keratotomy, used to correct keratoconus, the micro-incisions are only performed in the everted corneal sector, away from the pupilar field, from 30o to 270o. In 95% of cases, asymmetric radial keratotomy (when correctly carried out) is decisive for keratoconus.
It is an “out-patient” operation performed under local anesthesia (with collyrium), lasting about 1-3 minutes per eye, without bandages and leading to satisfactory results already by the end of the procedure. In most cases, a pair of sunglasses for a few days and the use of special eye drops to apply for a week post-op is all that is needed. In more recent years (since 1990), we have taken more steps forward, being able in fact to correct not only the progressive eversion of the cornea, but also its visual defect, nearly always in a more than satisfactory way.
Indeed, 80% of patients attain the maximum visual capacity without the aid of further corrective lenses; the remainder with the help of a simple eyeglass that, once the cornea has been normalized, is able to correct the patient in a satisfactory manner. In this way the patient, after the operation, is not only able to emerge from the tunnel of “contact lens > further corneal wear > corneal graft”, but also to have the best possible visual acuity. Thanks to my team’s long experience, the surgical application of this technique has undergone such development (given its extreme simplicity and nearly non-existent risk) that the operation is recommended at the first symptoms of the disorder. In fact, modifying the technique in a reductive way, the procedure is carried out with a number varying from 1 to 3 mini-micro-incisions of no more than 2 mm length and 70% depth.
One then succeeds in stopping the evolution of the disorder with the best refractive result, i.e. with the best natural or corrected vision. We are talking about the so-called mini A.R.K. (a variant that I often apply, and used according to the gravity of the cases). In this early stage, it is possible to guarantee a success rate of over 95% of treated cases, with several (8-10) years’ follow-up.
Asymmetric radial keratotomy has undergone development and improvement over time, so that today we can speak more completely of a “modular microsurgery for keratoconus”, i.e. “asymmetric keratoconus microsurgery” (A.K.M.), whose meaning is very simple. A.K.M. comprises a 3-Dimensional study of the zone of corneal wear with the use of special computerized programs to show us the inequalities of the wear zone as an orographic map (a geographical map with a scaled imaging of the different quotas).
Some incisions are applied on these gaps, and can vary regarding number, length, depth and spatial orientation, and be radial, tangential, oblique or curved. The choice really depends on the experience accumulated over the years, having operated thousands of keratoconus cases of types I and II and numerous type IIIs, plus hundreds of mixed astigmatic and/or hypermetropic-type keratoconus cases.
The use of such an evolved technique has in recent years permitted much more precise corrections and outcomes that are decidedly stable over time (more than 15 years’ stability). The technique is certainly safer and longer lasting in comparison with transplantation and represents the longest experience of an alternative technique to grafting.
And, in its rare cases of failure, does not jeopardize a possible future corneal graft.

Excimer lasers
The Excimer laser has a very important role when it comes to keratoconus because it allows a final finishing touch for any residual refractive defect in the operated patient.
It is my current conviction that it will be useful for the patient only if used in this way: with an ablation of a few (20-40) microns on corneas having good central corneal thickness (> 480 microns at the apex of the cone) and that have been stable for at least two years since the last A.R.K. or A.K.M. operation, with stable curvature radii and maps, and possibly <42 diopters.
Many illustrious colleagues are instead operating on keratoconus cases by performing ablation directly on the apex of the cone. I cannot share this surgical approach that results in thinning down an already thin zone whose pathology consists precisely in the excessive thinning.
I am convinced that where this technique is applied on eyes having “true evolutive” and not simply “worn out” (or stable, as previously explained) keratoconus, it can do nothing other than accelerate its inauspicious course toward an increasingly impelling and necessary corneal transplantation. Intrastromal rings
The recent application of this technique to keratoconus arose from the experience acquired with the same method for a “reversible” correction of mild-degree myopia (max 3-4 diopters). It consists in the inserting of semi-circular segments of P.M.M.A. (known by the commercial name of “Perspex” and already in use for over 50 years for the making of artificial crystalline lenses) into the thickness of the corneal stroma, at the base of the cornea, in at least 3-4 or more points on the 360o of the circumference.
These segments, having a larger inner curvature radius than that of the corneal segment, where they are inserted, exert a spring effect provoking a greater distension outwards, with an increase in the circumference of the corneal base, to which a flattening follows, due to the stretching of the corneal apex, with both subjective and objective improvement (corneal maps) in vision because of this induced flattening out of the cone’s apex.
This mechanism attains, certainly in the initial cases of keratoconus, an improvement in the patient’s clinical and refractive picture, but to repeat what we explained previously in connection with the pathogenesis of keratoconus: the worsening of this disorder is achieved due to thickness reduction of the collagen layers that are stretched (like elastic) under the pressing of the intraocular pressure.
Therefore this forced stretching of the cone’s apex can do no other than produce a further slackening and elongation of the collagen fibrils, caused by the excessive distension of the corneal base (just like the skin of a drum is stretched when it is pulled taut by the drum’s peripheral hoop that acts in such a way as to regulate its tension). That will give rise to a worsening, in a longer timeframe, of the keratoconus with a mechanism that I would describe as an “explosion”. Exactly opposite is the “implosion” effect produced by A.R.K. and A.K.M.
Provoking a collapsing on to themselves of the collagen fibrils, creating on the contrary a surface reduction in the apex of the cone.
All this with an immediate intra-operative effect then reinforced:
1) by the cicatrization of the mini incisions that, bringing repair tissue rich in fibrin, represent a stronger-knit structure that better contains the pressure pushing the cornea outwards;
2) and (especially) by the neoformation of healthy collagen fibril, developed via a biological mechanism known as “SILENT GENE” activation, which is able to take place only as a consequence of determined stimuli (in this case the incision and repair mechanisms that ensue), with the formation of “fetal” fibroblasts capable of producing young and therefore more transparent tissue than that of the adult patient and that goes to replace in time the diseased keratoconus tissue.
Such histological studies were already documented in the years 1986-88, with the aid of the electron microscope, at the Institute of Microsurgery of the Eye in Moscow, directed by my mentor, the late Prof. S.N. Fyodorov. It is further observed, as proof of what has just been formulated, that in all the cases of central and paracentral leucomas in keratoconus, such A.R.K.-induced cellular rejuvenation effects result in a clarification of the leucoma with restoration of the cornea’s natural transparency in almost the totality of cases treated.

Lamellar corneal graft
Another technique being attempted for the treatment of keratoconus is transplantation of the lamellar (thus not total or full-thickness) cornea. This procedure, undoubtedly more conservative than the classical graft, provides for the grafting of a donor corneal lenticular (deprived of endothelium and its basal membrane), mushroom shaped, that is enticed into a cornea hollowed out at its center by an excimer laser to about 300-350 microns.
At this stage the corneal graft is inserted (a bit like a champagne cork) and the outer rim, more everted, is then stitched on to the patient’s cornea of through 360 degrees, just like in the total transplantation.
This technique recalls “Kaufmann’s epikeratoprothesis” (no longer employed) with some changes that, in our view, make the procedure much more complicated than the original. Moreover, this technique’s field of application seems very rare to us, referring to initial keratoconus cases at the point of necessitating corneas at least 550 microns thick at the center (as reported by the authors). Such a thickness is exceptional even in initial keratoconi.
At this stage the surgeons propose a central circular excavation on such a cornea, carried out with an excimer laser, of 350 microns, necessary to confine the lens of about 450 microns’ thickness with a button-shaped corneal outline (thus more everted than a normal cornea). Being added to the patient’s residual 200 microns, this would form a cornea of 650 or more microns at the center. In our view, the technique’s complexity and extremely restricted number of potential patients do not justify the consequent loss of the patient’s visual acuity upon receiving such a graft, with transparency loss due to the double diffraction that the light undergoes in passing through two non-homogeneous bodies, plus the onset of irregular astigmatisms.
All this does not stand up to the comparison with A.R.K., which with its 2 or 3 micro-mini incisions of not more than 2 mm of length and 50% depth distributed away from the “unharmed” central optic zone that, in 2 minutes and under local anesthesia, returns perfect sight to the patient, without having thinned down his/her cornea, without having grafted tissue from another person and without complications of any kind.
Some colleagues that have badly interpreted my A.R.K. technique suggest to their keratoconus patients to go first for an excimer laser intervention to correct the irregularity of the corneal curvature (something debatable until the still unproven “topo link” system*) and then go subsequently to an A.R.K. operation.
Such original and unusual behavior would have as a “scientific explanation” the fact that in their view an A.R.K. used as the first operation would “destabilize” the keratoconus and that, done instead after the laser, would no longer “destabilize” it?!? NB: With A.R.K., we want to destabilize the keratoconus in order to be able to bring it back to a normal, regular corneal curvature! Then, it is extremely difficult for us to understand how a technique that destabilizes the keratoconus is able to do it at one time yes and at another time not, as if the therapy for this destabilization could be generated from the thinning of a tissue already in crisis because of too much thinness, through the use of the excimer laser.
We very much regret finding ourselves in an age of scientific and psychological inconsistency (where patients are used as guinea pigs for experimenting alternatives that are certainly “original” but scarcely scientific, putting forward captious and absurd explanations) to the point of pronouncing with Solomonic British spirit: “No comment!!” * Futuristic and not still sufficiently proven system of an interface between corneal topographer and excimer laser to be able to carry out an ablation exactly coincident with the zones of regular or irregular ectasia (see keratoconus) of the cornea, with a degree of extreme theoretical personalization for the operation.
(traduzione Dr.Aldo Magliocco - Milano)

Massimo Lombardi
Specialista chirurgo oculista
Università di Roma