History and Development

Nearsighted people have looked for ways to rid themselves of their glasses for centuries. Tradition says that the ancient Chinese slept with sandbags on their eyes to flatten their corneas. In the mid-1800's century Dr. J. Ball advertised an eye cup with small spring-mounted mallet that struck the cornea through the closed eyelid. "It restores your eyesight and renders spectacles useless.”
The idea of using glasses to change the refraction probably appeared in the 13th century by putting a correcting reading stone right in front of the eyes. This basic idea has been refined to today's one-day disposable soft contact lenses.

2.5.1The Keratotomy Experience

J. Lans, working in Leiden, the Netherlands, published in 1898 the results of his experiments in rabbits, employing keratectomy, keratotomy and thermokeratoplasty to treat astigmatism. After studying radial incisions, he enunciated the basic principles underlying keratotomy: 1. The cornea flattens in meridian of the incision. 2. Some of the effect is lost as the incision heals. 3. The incisions must penetrate deeply into the cornea to obtain an effect. Studies on the management of astigmatism with corneal surgery were also conducted by Italian and German surgeons in the late 1800's.

In 1933, T. Sato working in Tokyo observed by accident the flattening of a patient's cornea due to an acute break in Descement's membrane developed by a keratoconus. This gave him the idea of making incisions in order to cure keratoconus, astigmatism and myopia. His work was based on many anterior and posterior radial incisions into the cornea. Sato operated on approximately 680 eyes between 1951 and 1959. Studies in the seventies on a sample size of his patients showed that 86% developed bullos keratopathy due to the posterior incisions. The endothelium was absent. Sato stopped doing his myopia surgery as soon as contact lenses were introduced into his practice, before the rash of oedematous corneas appeared!

B.S. Yenaliev, working in the Soviet Union, was aware of the oedema that resulted from Sato's posterior incisions, and confined his research to keratotomy incisions through the anterior cornea only. Between 1969 and 1977 he performed his anterior radial keratotomy in 426 eyes. In 1972, S. N. Fyodorov of Moscow began studying radial keratotomy. In 1974 Fyodorov began surgery on humans. One of his most important observations was that sixteen incisions gave almost the same results as did 20, 24 and 32. Fyodorov and his college Durnev correlated their observations into a formula used to improve the ability to predict outcome for individual patients. Besides the diameter, the radius of the cornea and the diameter of the optical zone, the formula contains a surgeon's practical coefficient. Fyodorov became famous, as he had the greatest impact in Refractive Corneal Surgery, for example, his assembly line operation were shown all over the world. P. Siva-Reddy of Hyderabad, India, using this Russian technique had only poor results due to very superficial incisions.

Radial keratotomy spread inside the US in the late 70's by the promotion of Dr. Leo Bores. The technique was modified by various American scientists. They changed the direction of incision making centrifugally and reduced the number of incisions to eight and four.

In 1989 A. Arcienegas, Barraquer Institute, and the engineer L. Amaya, in Colombia developed the first, prospective approach of Keratotomy to correct myopia and myopic compound astigmatism [AA89].They based their biomechanical approach on tissue relaxation. With the calculated formula they could expand the surgery into the medium high myopic range and increase predictability. Until that time, the progress of radial keratotomy depended only on retrospective observations. However, even they had to go back to retrospective observations and stick to cluster like surgery calculation. Principally their technique encounters the same known problems of relaxing technique; as for instance, the long term hyperopic shift.In the future, however, studies only based on retrospective dimension will be too inefficient and even unethical. Systematic bio-engineering with the aid of today's complex computer simulations can minimize unexpected surprises and even reduce animal experiments. The medical "do it and see what happens" mentality shouldn't be strained to much because of being happy-go-lucky and of missing prospective studies.
2.5.2The Early Keratomileusis Experience

Keratomileusis is strongly sticked to the father of modern Refractive Corneal Surgery Jose I. Barraquer. Barraquer has made numerous contributions to ophthalmology in general and in Refractive Surgery in particular. He dedicated his life to the dream of correcting ametropia when virtually no one else could or would respond the same calling. He first announced that refraction could be changed by remodelling the radius of curvature of human cornea in his doctoral thesis in Spain in 1949 [Bar49]. He moved to Bogota in 1953, leaving the families' clinic in Barcelona. The law of thickness was introduced by him in 1964 [2.2.3]. Later, he established the Instituto Barraquer de America and until now he is the honorary President of the International Society of Refractive Surgery (ISRS). [Nor89, Bar96]

Long before the great rush of radial keratotomy he realised that the correction of refractive defects should not depend on hopefully placed incisions and cicatrical retraction of the wound, as in Sato's keratotomy. Instead he demanded a process that permitted a predetermined result of the greatest possible accuracy on an organ in permanent regeneration [Bar67p.31]. His methods always aimed for precise optical correction by means of exact mathematical surgical interventions. He designed and fashioned his own equipment in various fields of refractive keratoplasty. Moreover, he invented and named many of these procedures like keratophakia (intracorneal lens) and keratomileusis. After extensive experimentation with corneal grafts, plastic corneal inlays, and limbal alterations, Barraquer realised that more permanent, predictable surgery could be accomplished only by changing the shape of the cornea itself.
 

2.5.2.1 Keratomileusis Procedure

Queratomileusis significa
cinelado o tallado de la córnea.

Queratom'ileusis, palabra derivida del Griego
Queratos: cornea, mileusis: cincelar.
Jose I. Barraquer[Bar64p.27,p.48]

Keratomileusis refers to a any refractive corneal procedure that uses subtraction of tissue with refractive means.

The first successful keratomileusis technique goes back to the year 1964 and was determined by lamellar resection, extracorporally cutting of corneal tissue lenses in a lathe [Bar67, Bar64]. At that time this technique unlike other keratomileusis techniques (plane section in corneal bed, plane section extracorporally and others) allowed maximum precision by mathematical calculation. However, in applying this technique, the jelly like corneal tissue needed to be hardened, before resectioning on the lathe. Principally there were three ways of hardening the cornea [Bar67]: 1. freezing, 2. desiccation or 3. increasing the lineal velocity of cutting. Freezing the corneal tissue brought best results with less damage to tissue, therefore this keratomileusis technique is commonly known by freeze keratomileusis. In the beginning the calculations were done longhand in the operating room, but Barraquer moved quickly to procure the first programmable calculator to calculate the shape of excision and to shorten the surgical process and improve its outcome. He later advanced his technique by constructing a compressed air turbine cryolathe and a computer guided cryolathe3. He applied this technique with remarkable results up into the 90's on about 3000 (!!) high myopes.

2.5.2.2 The Microkeratome and It's "Flap"

Before innercorneal tissue can be reshaped either intrastromally or outside the corneal bed, the anterior layers of the cornea must be hinged.

Barraquer invented the microkeratome fulfilling this difficult task. His microkeratome consisted of a suction ring hardening the cornea by maintaining the intraocular pressure above 65 mm Hg to allow a smooth cut. The anterior layers of the cornea were either hinged (flap) or even totally capped. The prototypes were made of brass. Later the American Steinway company manufactured a stainless steel version.

The hinged flap and the use of the microkeratome have had a great impact on newer developed Keratomileusis techniques, in particular LASIK. Barraquer's protégé L. Ruiz further developed this microkeratome with a motor drive to simplify the cutting procedure. Today this microkeratome is sold by the Chiron company. Although this microkeratome takes all the Barraquer's experience into account, Ruiz named it Automated Corneal Shaper to avoid any association with its origin.

2.5.2.3 Various Definitions of Keratomileusis

As already mentioned earlier keratomileusis refers to any refractive corneal procedure that uses subtraction of corneal tissue with refractive aims. However, depending on the context, the word is used in different manners. Sometimes, it stands only for the original procedure called freeze keratomileusis. Most commonly any intrastromal subtraction with a microkeratome is referred to as keratomileusis. The superficial PRK is often not associated with keratomileusis, although it holds the definition criteria.
The use of the microkeratome is strongly associated with keratomileusis due to the historical development. Some would easily call all procedures keratomileusis which take advantage of a microkeratome. Although the microkeratome is involved in intrastromal keratomileusis, not all the techniques using the microkeratome are keratomileusis procedures. For instance, Ruiz's technique of ectasie to correct hyperopia -using a microkeratome- is a non keratomileusis technique, as there is no resection of tissue and the law of thickness is not applied.

The following graphic summarises the different levels of keratomileusis. All procedures in the big circle are keratomileusis procedures. Further specification is reached by separating intrastromal procedures from superficial procedures. Absolutely non keratomileusis techniques such as the technique of ectasie and radial keratotomy are outside the circled ring.
 

2.5.3 The Photorefractive Experience

In practise excimer, photorefractive and Laser Refractive Surgery seem to be different words for the same thing. Here, the Photorefractive Surgery using an excimer laser is introduced.

2.5.3.1 History

Argon fluoride excimer laser were first used for the production of computer microchips. R. Srinivasan and others described a very exact ablation of plastic materials with the excimer laser in 1982 [SM82]. Parts of the technology used were developed in 1976 and the patent rights belonged to IBM. S. Trokel and R. Srinivasan described laser ablation on cow cornea in 1983 [TSB83]. T. Seiler first applied laser ablation on human cornea 1985. In the beginning he tried to use the laser to make the incisions used in keratotomy. As photoablation always involves the excision of tissue, results of laser keratotomy were poor. He realised that the excimer laser must bring better results when doing excision of whole areas of the cornea. Seiler was the first who applied laser ablation on a well functioning eye in 1987 [Sei86]. From then on, many scientists started to apply laser ablation for Refractive Corneal Surgery. The abreviation PRK stands for photorefractive keratectomy, that is to say the excision of corneal tissue by laser ablation for refractive means. Strictly speaking PRK only presents a surgical instrument for Refractive Corneal Surgery like the microkeratome. PRK can be used for superficial excision or intra stromal keratomileusis resulting in LASIK. However, since the beginning, PRK has been applied superficially. Therefore when speaking of PRK, most ophthalmologists think of the superficial PRK procedure.

2.5.3.2 Argon-Fluorine Excimer laser

instrumentation
The excimer laser consists of an energy source, a delivery system and a controlling unit. The term excimer is derived from the words excited and dimer. Within the energy source, argon-fluorine (ArF) atoms or ions are excited through the application of electrical energy. These energised atoms emit photons of light. This beam then passes through a series of mirrors and prisms to enhance the optical qualities of the beam. Researchers have developed several systems to deliver the beam to the cornea in the desired profile. When correcting myopia the central portion of the cornea receives more ablation then the periphery. For instance, a diaphragm delivery system, gradually opens at pre-programmed intervals to control the diameter of the beam.

Two basic types of excimer lasers are sold, depending on the kind of delivery system: whole field or scanning. The whole field approach often use a simple diaphragm delivery system. The scanning approach requires more complicated delivery and control systems, but the energy source can be much smaller.

Typical characteristics are the frequency of pulse repetition (5 to 20 Hz), power (120 mJ/cm to 400 mJ/cm) and the possible diameter of treated optical zone (4 mm to 9 mm).

tissue/beam interactions
Lasers have been used in ophthalmology for more than 25 years due their four unique properties: tight direction, high intensity, coherence and purity. However, depending on the laser's wavelength tissue interaction differs. Photons produced by longer wavelengths are relatively low in energy, while those produced by shorter wavelengths are relatively high in energy. Therefore, tissue interactions can be photodisruptive, photothermal or photochemical.

The excimer laser is of relatively short wavelength, 193 nm. It is a UVC beam producing photochemical interactions cleaving the cornea's carbon to carbon bonds. This interaction is a form of chemical photodecomposition, a process more commonly known as photoablation. The photochemical interaction is the most precise tissue removal; as its effect is non thermal and non disruptive, and surrounding tissue is neither burned nor damaged. Each pulse removes only partial areas of tissue with a 0.25 µm depth. This precise interaction allows the removal of the cornea's tissue in it's optical center without diminishing the vision. Although the removal is discrete, the precise removal of 0.25 µm tissue steps ensures that all light wavelength's pass through without distortion.

The ablation process causes a reverse impulse of up to 107 Pa, these wave fronts might imitate the retina if fragile, operation therefore shouldn't be applied shortly after retinal surgery. However, other parts of the eyeball will not be affected, as the wave resistance hardly changes passing the different mediums.

mutagenicity
Although the 193 nm excimer beam effectively removes corneal tissue we must consider the safety of this UVC radiation. About 95 % of the energy of the 193 nm beam is attenuated within the corneal tissue within 1 µm, and in most cases the nucleus will be not be reached. However, secondary radiation of about 200 to 300 nm could also perform mutagenicity. Numerical estimations show that this radiation is below a factor of two from the critical 10 µJ/cm2 mark. Over 300.000 treatments without diagnosed neoplasm confirm the safety in this aspect. 40-60 µm below the treatment zone there will be no keratocites. However, this effect occurs just as often by simple abrasion. Within weeks and months keratocities come back and after a year the normal proportion is reached.

2.5.3.3 The Superficial PRK Procedure

Conceptually the superficial PRK procedure applies the thickness law by superficial keratectomy (excision). After patient selection and different examinations the patient will be treated ambulantly with local anaesthesia. Before laser ablation the epithelia will be removed either manually or with the laser. Then laser ablation is applied. After surgery the patient usually gets steroid and non-steroid antiinflamatopry agents to control wound healing. After three months vision is mostly recuperated and after a year refraction is stable. Haze and halos are typical during recuperation time.

2.5.3.4 Results of the Superfical PRK Procedure

Results have been quite promising, however, its interpretation strongly depends whether the treatment is applied to patients, or people who just prefer to get rid of their glasses or the daily contact lens procedure.

Results can be measured either by individual satisfaction or by standardised measurements. Measurement of individual satisfaction is very important for future patient selection. Standardised measurements allow comparison, scientific progress and direct quality control. Discussion of this theme is one of the major topics of this work, a solution will be developed in the sixth chapter. Presentation of superficial PRK results will give a practical introduction to finding proper quality indicators.

Common standardised indicators are uncorrected vision, best glass corrected vision, best lens corrected vision or best corrected vision, either expressed in relative loss/gain of lines or in absolute index form. However, all these indicators only measure vision in certain conditions, which neglect many other common circumstances of vision. Some of the contradictions between patient satisfaction and these measurements are due to today's clinical testing.

The superficial PRK procedure seems to be splendid when measured by the improvement of the uncorrected vision index . Every person gains in uncorrected vision and often can handle daily life without vision aids after surgery. Changes in bestcorrected vision with common measurements seem to be insignificant in the medium time range, if superficial PRK is applied in proper patient selection. In the short range, during the first three months, sometimes until a year, best corrected vision is reduced significantly, due to haze from the healing process. Although life time experience so far does not exist, clinical approximation does not expect a loss of vision once the results have stabilised.

Deviation from emmetropia is another internationally common indicator. The surgery is rated successful, if after one year the deviation is in-between ± 1 dpt. from emmetropia.