Keratoconus is a degenerative disease of the cornea that can be highly disabling over the years. It affects one in 500 people, more or less severely, with a higher incidence among young people, teenagers and children.
If not promptly diagnosed or not treated properly, it can lead to corneal transplantation. It is a highly debilitating disease as it affects patients with high life expectancy and with good vision.
The modern diagnostic and therapeutic strategies developed in Italy help to diagnose the disease early and to block the evolution and the resulting future damage to vision, as well as to the quality of life of the subject.
Dr. Bellone what are the symptoms of this disease?
Symptoms can be diverse: usually it is manifested by a gradual loss of vision, astigmatism and myopia, night halo effects and eye rubbing. The cause of the disease is still unclear, but there seems to be a genetic predisposition (shown in 10-15% of cases). Within the same family this disease affects the various members in a “patchy” way, it is usually bilateral (85%) and severity can vary from person to person.
Dr. Bellone, why should this disease be diagnosed early?
Keratoconus more frequently affects young subjects, adolescents or children. By affecting people at a young age and therefore with a long life span the social impact of this disease is significant.
Keratoconus greatly reduces the quality of life and has a terrible psychological effect on the patient. If I told you that you are suffering from a disease that can not be cured, but can only get worse in time, how would you feel?
We must also clarify the term “disabling”: I think for a young patient to begin a long series of visits, of glasses, of contact lenses that then are not a true therapy, a pilgrimage to various specialists that can go on for years until a corneal transplant, is debilitating because it conditions the quality of life for a number of and for too many years.
And so what can we actually do?
First, focus on early detection. Being able to diagnose the start of keratoconus in the eye of a very young patient, maybe 12 years old, gives us a significant advantage over the disease and we can prevent some damage from occurring, rather than settling for not having it progress after it has occurred.
Is keratoconus difficult to diagnose? And is it more difficult with young subjects?
The advantage is that the diagnosis can be performed in a common ophthalmology clinic equipped with a corneal topographer. The most important thing is that the ophthalmologist is trained to interpret the images correctly, especially during the first signs of the disease. As with all early diagnosis efficient instrumentation and trained operators can make a big difference.
That’s why it is essential that patients gain access to specialized centers for the diagnosis and treatment of keratoconus in order to avoid misinterpretation and incorrect diagnostic treatment advice.
When diagnosed with keratoconus what is the best treatment?
I would not say best therapy, but a set of therapies that used properly can give us the best possible outcome for the framework of the individual patient. We must make good use of the weapons we have available.
Iontophoretic transepithelial corneal cross-linking is definitely one of the best weapons we have available to halt keratoconus.
Is cross-linking treatment painful?
No, it is a painless therapy and treatment times have been significantly shortened thanks to the perfecting of a successful method already widely in use.
It involves the absorption of the medicine, riboflavin or vitamin B2, inside of the ocular tissues by means of electric current at low voltage for 5 minutes.
The use of electric current, for the first time in a medical intervention, allows to obtain very high concentrations of the drug within the cornea.
Iontophoresis allows the medicine to be absorbed by the tissues in an active manner, that is, following the flow of current which carries it like train wagons carry cargo. The electric current makes it more effective: the absorption of the drug becomes much quicker and effective and time is greatly reduced, it only takes 5 minutes.
Following absorption there is a phase of irradiation of the cornea with ultraviolet UV rays for 9 minutes.
The combination of riboflavin and ultraviolet rays (both natural and available in nature) creates a chain of reactions within the cornea which lead to the formation of new corneal collagen which is healthy and not degenerated like the cornea affected by keratoconus.
Cross-linking treatment serves to create a new corneal connective tissue matrix that is more robust and functional than that of the diseased cornea.
It is a procedure free of contraindications, repeatable, performed in an ophthalmology clinic. The final result is really optimal, so much so that it can also be used with children.
Are there are other treatment options besides cross-linking and iontophoresis?
Cross-linking is only one of the cards that the ophthalmologist has available. Its function is to stop the progression of the disease, but it only acts minimally on visual defects: if a patient has become myopic and astigmatic due to keratoconus glasses cannot be eliminated following cross-linking.
So is it possible to eliminate glasses in some cases?
Over the past 20 years we have developed a surgical technique that allows for the reversal of the keratoconus to an earlier stage and thus to improve vision defects up to eliminating glasses in the most favorable cases.
The technique of implantation of Ferrara intrastromal corneal rings is ambulatory with surface anesthesia using drops. The patient goes home immediately after the surgery and already the next day can start a completely normal life.
The insertion of the rings can be performed with the help of a femtosecond laser, which is a laser capable of cutting transparent tissue with a blade of light guided by a software that can create any design in the corneal tissue.
Of course the insertion of intrastromal corneal rings must be followed by cross-linking treatment. The two techniques are mutually supportive and give optimal results when performed by highly specialized personnel.
The latest addition is the 340 ° ring essential for nipple-type keratoconus, of which I have carried out the first implant in Italy. It is a ring that is almost complete except for 20 ° which serves to be able to insert it into the corneal tunnel created beforehand with the femtosecond laser.
There are also patients who have high degrees of myopia or astigmatism. Are there no options for them at the present time?
A very interesting technique has been developed that is reserved precisely for the cases of keratoconus that are accompanied by high myopia and astigmatism and have been stable for a long time. In these cases ICL phakic lenses are implanted which are special intraocular lenses that do not need to be removed and can effectively carry out their function for a lifetime.
When I discovered that I have keratoconus, I initially had a little bit of fear and anxiety but when I was told about the existence of the treatments for this disease, I calmed down. On my right eye, I had a ring implanted and the surgery was completely comfortable. The doctor’s team, the surgeon, all of them made me feel comfortable. They did help me overcome my fears when I was about to enter the operating room.
The surgery was smooth and easy, thanks to the anesthesia and in fact, I did not notice anything unusual and it seems that it was very short. The postoperative period was initially a little bit bothersome because of the bandage but once that bandage came off, everything got better and I had noticed my eyesight’s recovery.
My left eye underwent Cross Linking and as I’ve said, the surgery was not at all bothersome. The postoperative period on this left eye was a little bit longer but it was still manageable because of the Acetaminophen.
The surgery that was done with the ring was intended to flatten the cornea and eventually give the cornea a more physiological shape that was more similar to that of the left eye. Surprisingly, now the right eye, which used to be the worse eye has become the better one.
The patient is still advised to wear glasses since both of the eyes had a slight myopia to start with and the ring does not have a pure refractive purpose. That is to say that it is not like a laser surgery, so the effect of reducing the vision defect is secondary and the myopic patient stays myopic. At the most, the astigmatism related to the keratoconus may be eliminated.
The operation was done with the assistance of the Femtolaser, so we created the tunnel of the ring implant with a laser machine and have put the ring in place. All lasted two minutes and a few seconds. The patient has distinct characteristics like very large pupils because of his young age, therefore they usually fit poorly with the implant of intrastromal rings, so we instead implanted a large diameter ring (of 6 mm), which reduces the effect of nocturnal halos to a minimum.
Like I said, the surgery with the ring lasted a few minutes. In the postoperative period, he understandably had a little bit of discomfort because of the bandage that keeps the eye closed, just like our patients who were operated for cataracts and the result, once the bandage was taken off, was immediately very good.
On the other eye, we did Cross Linking with iontophoresis, which is a special Cross Linking procedure. It lasted fourteen minutes and we had the riboflavin absorbed with electric current. After which, there was the exposure to the ultraviolet rays for nine minutes. This iontophoresis procedure is an Italian patent and is an absolutely revolutionary method to make the substance penetrate inside a tissue. Such is done since the substance is not swallowed, not injected intravenously, nor not with a suppository. The substance is absorbed through a small electric current.
So this is a great revolution. We do not need to remove the corneal epithelium (the upper layer cells), so we leave them intact and avoid all the risks of traditional Cross Linking.
It is advised to rest for at least 24-36 hours and it is important to emphasize that our patient has not completely recovered because keratoconus is a permanent disease. However, above all, we have managed to stop its progression. We have operated without risk and we have postponed the day when the disease could unfortunately get worse. Therefore, doing what we did is the best thing to do. Maybe in 10-15 years, a new method will come out and he will have an eye that has not deteriorated, all thanks to what we did today. We have taken advantage of the new available techniques we all have just mentioned.
We finally have the new 2018 nomogram classification that is related to the treatment with intrastromal rings for keratoconus.
The philosophy of the new nomogram classification states that each keratoconus is unique and therefore, should be assessed individually and systematized to define the best and most appropriate surgical approach, subsequently produce a detailed analysis of multiple topographic, refractive, visual, and aberrometric variables that are all essential to create a good plan of surgery to satisfy both the surgeon and the patient.
There are many available intrastromal rings today and the parameters that distinguish them from each other are, basically, the diameter, arc, and thickness. For what concerns the diameter, we have the possibility to choose between a diameter of 5 mm and 6 mm and this choice is dictated by the mesopic conditions of the patient’s pupil so as not to create too many nocturnal aberrations and halos around lights.
The second parameter is the arc, that is how many degrees the arc extends the ring and we have an initial parameter that is of 90°, then 120°, 150° or 160° that are in accordance to the optical zone. We may also go to the less common choice of 210° and, finally, the 325° arc which is classified as a 5 mm ring, even if in reality it has a diameter of 5.7 mm and therefore is an intermediate condition.
To these variables, we add a third one, which is the thickness of the rings that varies from 150 to 350 microns with a pitch of 50 microns, so, practically, for each of those we mentioned before, there is the 5 mm and 6 mm version with arcs of 90°, 120°, 160°, 210° and 325° and for each, there is a specific thickness available. These determine how much correction we are going to make with the intrastromal ring and how difficult it is to choose the appropriate one to correct our keratoconus.
A new challenge has recently been added. A new variable that is of the possibility of having asymmetric rings is now another difficulty and it is born from the fact that keratoconus is a disease in which by definition the cornea takes on an asymmetric appearance but in its asymmetry, it is usually symmetrical and this means that the deformation of the cornea usually has a symmetrical pattern and is, therefore, corrected quite well with a variable thickness ring. However, this does not happen if there is a corneal deformation of an asymmetric type (and later we will see which are the most common characteristics of asymmetric keratoconus). Here, we have the need to create asymmetric intrastromal rings that have a variable pitch and begin on one side with a specific thickness and a different amount of thickness on the other end.
These types of rings are luckily available only in the arc version of 150° for 6 mm and 160° for 5 mm, so all the other ones are inaccessible (122, 210, etc.) and are difficult in addition to the fact that this increase in thickness may be clockwise or counterclockwise. What we have is the clockwise version (that has an increase in thickness of the ring in the clockwise direction) and the anticlockwise version (that has an increase in thickness of the ring in contrast to the clockwise direction).
The new version of the asymmetrical ring 330° is added to the asymmetrical ones: it is also 5 mm, therefore its optical area is 5 mm (even if it is actually 5.7 mm) and the characteristic of this ring is increased thickness, moving from 150 to 250 or from 200 to 300 in the AS5 330° version, thinner at the tips and thicker at the center of the arc.
The latest version is the variable ring with sinusoidal thickness and an arc that is always at 330° is in the versions 150/250/150 or 200/300/200. It has a sinusoidal or inverted profile and can be thin at the tips and at the center of the arc and thick at the intermediate portions or thick at the tips and center of the arc and thin at the intermediate portions. With this, we can see how the correction of nipple cone keratoconus, with central ectasia, has become a custom.
The table tries to represent all the available rings, so we have the beauty of 67 variations of arc, thickness, and optical zone, so you can correct any type of keratoconus and therefore allow for greater customization of our surgical plan.
The new 2018 nomogram of the intrastromal rings allows to create a new criteria for the selection of the optical zone, implant axis, and, above all, the measurement of the ring that will be implanted; it goes to fill the gap that was left by the old nomogram in 2009, so in 9 years we did not have a nomogram upgrade and only allowed us to use the 2009 version.
Thanks to our Spanish colleagues, the new nomogram is finally made available to everyone.
What are the data required to be able to do a surgical plan and calculate the ring to be implanted? First of all, a corneal tomography in four maps, an axial curvature, anterior and posterior elevation with the best fit spheres and a pachymetric map; naturally, it must be accompanied by an aberrometric topography with magnitude and coma axis and obviously the surgeon must be able to determine the subjective refraction and above all, pay attention to the correction of the maximum theoretical negative cylinder which allows us to correct the refraction defect.
We have to determine the visual acuity, whether it is with correction or without correction, the pupillary diameter in mesopic conditions, and the potential visual acuity with contact lenses or with pinhole; of course, you need to decide which surgery technique will be used, that is, whether manual or with femto and at the end of everything, determine which type of keratoconus we are facing according to the morphological classification of Fernandez-Vega Alfonso.
The new morphological classification of keratoconus allows the implantation of intrastromal rings and is proposed by Luis Fernandez-Vega and José Alfonso of the University of Oviedo in Spain.
Basically, there are five types of keratoconus that are defined by some variables; first of all, where is the cone located?
Then, it is very important to understand what is the relationship among the three axes (flat refractive, flat topographic, and coma); finally, it is important to understand the astigmastism topographic orthogonality and symmetry and the topographic appearance of the curvature map.
The first parameter to be determined is where the cone is: measuring the distance from the center to the apex of the cone on the posterior altimetric topography, it may be in a central, paracentral or pericentral position depending on whether it is less than 0.75, between 0.76 and 1.80 or more than 1.81 mm from the center.
Then, you have to determine the relationships among the three main axes, namely, the topographic, refractive and the comatic axis.
The topographic axis is the flattest axis in the anterior corneal topography. It is the one which we put the negative cylinder in where the patient achieves the best visual acuity and remember that the latter goes to correct the coma because this comatic aberration that characterizes the keratoconus basically corrects itself by pretending, mimicking a comatic correction but not having lenses to correct the coma. We correct it with a cylinder. Therefore, in a symmetrical keratoconus, the axis of the coma usually corresponds to the negative axis of the negative cylinder that we are going to correct but not in all cases, of course. In fact, the comatic axis, which is the one that is found with the aberrometric map, is the third axis.
These three axes can be coincident, the comatic axis may also not be coincident with the topographic and the refractive axis or the comatic axis and the refractive axis are coincident, as it often happens, but perpendicular to the topographic axis. Putting these altogether, the three axes determine what kind of keratoconus we are going to have.
We also have the orthogonality of the astigmatism, which means we measure the angles between the lobes of the topographic astigmatism, so we can have a regular shape if the angle is below 20° or an irregular one if the angle among the lobes exceeds 20°.
Another very important parameter to verify is the symmetry between the lobes of topographic astigmatism. When the lobes have similar shapes we speak of symmetry, whereas they are asymmetrical when the lobes are different in sizing.
The identification of the type of ring to be implanted in the case of keratoconus of phenotype 1 called “croissant” is relatively simple: we start by understanding the radius of curvature of the cornea, so up to 52 diopters we can use 5 mm, above 52 diopters we must use 6 mm and we recommend using 6 mm also in patients with particularly large pupils. Always remember that the 5 mm ring has a flattening capacity greater than 6 mm, hence the choice of 5 mm when the curvature rays of the cornea are very high and/or when the patient is very young and/or when the keratoconus is be very aggressive.
That being said, the arc of implantation is always 160° for the 5 mm and 150° for the 6 mm and this can induce a little bit of confusion but you will soon get used to it.
So we understand that the ring to be implanted is 5 or 6 mm, the arc is that of 150° or 160°, what remains to understand is what is the thickness that varies depending on the astigmatism that we have to correct, so there is an easy-to-interpret table that tells us that up to 2.5 diopters, 150 micron thickness is placed, between 2.5 and 3.5, 200 microns, between 3.5 and 4.5, 250 microns, 5 diopters of astigmatism it takes the 300 and above the 5 diopters it is necessary to associate the 300 microns with a 90° thickness ring, 150, 200 or 250 microns of increasing thickness.
The keratoconus phenotype 2, also called “duck” has the characteristic of being an asymmetric keratoconus, therefore a paracentral localization; the relationship between the topographic and coma are not coincident, the orthogonality of the astigmatism is irregular and the astigmatism is by definition asymmetric.
In this type of keratoconus the progressive or asymmetric rings are used; also in this case, if the radius of curvature of the cornea is below 52 diopters, an asymmetrical segment 160 or two segments is used: an asymmetric 160 plus a standard 120 in accordance with astigmatism; obviously, if the refractive axis coincides with the topographic one, the bisector of the axis is used, if the refractive axis coincides with the coma, the bisector is used.
The astigmatism determines the power of the ring, therefore under 4 diopters, a ring with variable power 150,250 and between 4 and 6 diopters, 200,300; above 6 dioptres of astigmatism, it is associated with 200,300 and 120,200 microns.
If the keratoconus duck has a mean keratometry above 52 diopters, a new 330° asymmetrical ring is used in accordance with the average curvature, therefore an AS5 330°, 150,250 progressive from 52 to 54 diopters of corneal curvature; above 55 diopters, an implantation of 330,200,300 microns.
Type 3 keratoconus, the “snowman”, is divided into two sub types: type 3A and 3B.
Both cases are either paracentral or pericentral in localization with a topographic axis and a perpendicular coma axis. The orthogonality of the axes is regular but they are asymmetrical.
This type of keratoconus snowman has the characteristic of having to be corrected with an asymmetrical ring. In cone 3A, we distinguish it with its appearance of a snowman with a small head and big belly. Obviously, we have to do more correction in the belly area and less on the head area. Given the symmetry of the axes, it is necessary to implant two rings that embrace the snowman, however, we must distinguish if the mean keratometry is below 52 diopters, then we implant two asymmetrical rings of 5 mm in diameter, 160° of arc and 150,250 microns. On the other hand, if above 4 diopters, we will implant 200,300 microns.
We have C and W where C stands for “counterclockwise” and W stands for “clockwise”. In my mind, I try to remember that C is the thickness that runs opposite the direction of the clock. Usually, it is implanted in the right eye, so I mentally associate ring C to the right eye and the W to the left eye. This is just a silly association that serves as my quick remember but in reality, we must always understand the cone and where it is most often, where we need to make more correction so as not to make a mistake of putting the wrong ring.
If phenotype 3A shows a mean keratometry between 52 and 54 diopters, then it must be corrected with a 330° asymmetrical ring with a variable thickness of 150,250 microns. If mean is above 54 diopters, then correct with a ring of 330,200,300. The difference with the two asymmetric implants is reduced to a minimum because of implanting two asymmetric kissing rings. We use 330 to correct higher dioptric powers, therefore a more evolved keratoconus because, obviously, it has more force in flattening the cornea.
Finally, if we have a 3B sub type of keratoconus snowman, which is the one in which the snowman’s head does not exist, there is only the belly, we use a 210 (this is one of the few cases in which the 210 ring is still used). Depending on the coma we must correct, we implant a 200, 250 or 300 micron ring if the coma is below 1.5, between 1.5 and 2.5, or above 2.5 microns in the area of 5 mm, respectively. Therefore, the aberrometric map with the measurement of the coma is essential in this type of identification.
The type 4 keratoconus, also called keratoconus “nipple”, has the characteristic of being spherical so there is no astigmatism, the localization is central, there is no relation among the axes of astigmatism and it is certainly not a determinable astigmatism.
In this type of keratoconus, we have to use a 325° arc ring and in diameter E65, which is also the only one available. The thickness of the ring is variable depending on the sphere that we must correct and remember that the defect of sight of this type of keratoconus is spherical and myopic, so to correct 3 dioptres we put a 150, to correct 5 dioptres we put a 200, 7 diopters a 250 and above 8 dioptres a 300. This is if visual acuity is determinable, if mean keratometry is 48 diopters, we put a 150 micron, for 49 diopters a 200, 52 diopters a 250 and over 52 diopters a 300.
Personally, I am used to thinking in diopters of visual defects, so I tend to try to measure the patient’s refractive defect in the most appropriate way.
Keratoconus with phenotype 5, also called “bowtie”, is a keratoconus whose characteristic is to present a very symmetrical small hourglass astigmatism. It has a central localization, the relationships among the axes are of the coincident type between the refractive and topographic and the coma one is non-determined. The orthogonality of astigmatism is regular and symmetry is symmetrical.
In this type of keratoconus, it is obvious that we must act, above all, on the astigmatism, so we must go and implant two rings that embrace the small hourglass and what are the parameters to understand which rings to implant? First of all we need to see what the mean keratometry is. If it is below 52 diopters, a 6 mm ring can be used; if the refraction is a mixed astigmatism, it is necessary to use two 2 symmetric segments of 90°. If the refraction has a myopia inferior to the two diopters, it is necessary to use two symmetric segments of 120°; if the refraction has a myopia of greater than two diopters, it is necessary to use two symmetric segments of 160°. So, myopia has, in this type of keratoconus, a decisive role in choosing the arc. The more it is towards myopia, the more we put a complete ring. The less myopia to correct, the more we put a reduced arc ring. Therefore, the reduced arc rings correct more astigmatism while the more complete rings correct myopia. If the astigmatism is less than 4 dioptres we put a 150, if we have to correct 5 dioptres, then a 200 one, 7 dioptres with 250 and above 8, a 300.
Finally, this table determines the limits of the corneal thickness we need to implant a ring onto. It is necessary to determine the minimum thickness of the cornea in the area where we are going to create the pocket. We can do this with topography and then we must be sure of being in a margin of safety. For example, if we want to implant a 250 micron ring, we need to be sure that we have a stromal area of our tunnel of at least 420 microns.
We can recommend to customize our ring system as much as possible, to rely on competent people who can give us advice because they have implanted so many. The same company provides a website and an application to rely on.
I can still give you a couple of tips when it comes to implementation. For example, use a topographer that has a ring simulation program inside. This has a Scheimpflug camera or OCT that work the same way. Then, with the software, you can create a pachymetric topographic map, outline the ring, and understand how much depth is needed, what arc to use. In short, you can put all the parameters in order to understand if you have a safety margin, the thickness of the tunnel area and the thickness of the ring that you can implant.
Always take into consideration what the bisector the instrument provides you. It usually coincides with the axis of the coma, so the concept is that the ring must embrace the coma and support the ectasia and therefore the somatic deformation of the cornea.
I usually calculate with a calculator the point where we must go to make the vertical cut in the cornea to insert the ring. This vertical cut should be made at least 20° away from where the ring begins, so, for example, if we have a 270° bisector and our ring has 160°, you add up to 270°, 80° on one side and 80° from the other. From the temporal side, add 20° again, so if it is a right eye to 270 (which is the bisector) subtract 80, which makes 190, we remove 20 more that makes 170 and then, we will have to cut to 170. Then our ring will have an entry in the cornea at 170°, it will start at 190° plus 80 which makes 270 and at 270, it will reach the bisector, so it will be the point where the belly of the ring coincides with the bisector. Add another 80° and we have the end of the ring, then 270 plus 80 makes 350.
Here is how I usually do the calculations.
Another trick is to mark with the marker in the preoperative phase (and never mark it intraoperatively) these points, then the entry point and the bisector, to understand where to place the ring. For the majority of femtoseconds, I recommend to also mark the 0180 because the suction ring has two cleats, usually 0180 and then you can align the 0180 with the 0180 of the cup.