Photorefractive keratectomy (also referred to as wide area ablation, corneal reprofiling, corneal sculpting, and laser keratomileusis) is the process of using the Excimer Laser to reshape the cornea in an effort to effect a change in the refractive characteristics of the eye and thereby correct or lessen myopia (nearsightedness), hyperopia (farsightedness), and/or astigmatism. Using the Argon-Fluoride Excimer Laser to accomplish photorefractive keratectomy is a dramatic departure from existing refractive procedures. Some of these existing procedures include radial keratotomy, in which multiple deep radial incisions or cuts are made into the cornea with a diamond blade; epikeratophakia for myopia and hyperopia, in which a donor corneal lenticle is reshaped with the corrective prescription and then sutured over the patient's own cornea; and myopic and hyperopic keratomileusis, in which the patient's own cornea or a donor cornea is shaved and reshaped like a contact lens with a corneal lathe and then resutured onto the eye. (Current technological offshoots of keratomileusis include myopic or hyperopic Lamellar Keratoplasty) and Excimer Laser PRK with the microkeratome, or LASIK.)
In photorefractive keratectomy for myopia, hyperopia, and astigmatism, the cornea is reshaped by the Excimer Laser without being cut or incised, normally effecting a change in the refractive properties of the cornea. The Excimer Laser uses photoablation, or high-powered, pulsed ultraviolet radiation (light energy or photons) to remove tissue with an extremely high degree of precision. The Excimer Laser is a unique computerized 193 NM Argon-Fluoride laser which can reshape the front surface of the eye (cornea), acting at the atomic and molecular level, in as little as 20 seconds, without creating significant thermal damage to surrounding tissue. This special characteristic allows the Excimer Laser to be referred to as a "cold" laser. ("Cold" is a relative term, in that other lasers produce larger amounts of heat and thermal damage than does the Excimer Laser.)
In an area of the central cornea, about the diameter of a drinking straw, 25 billion million photons (packets of light energy) per pulse shower down in a parallel fashion onto the cornea, photoablating, or removing, .25 microns of tissue with each laser pulse. [One micron equals one one-thousandth of a millimeter (1/1,000).] One cell (10 microns) has to be hit or pulsed 40 times in order to be completely photoablated at .25 microns, or 1/25000 of an inch, per pulse. The number of pulses needed to correct the myopia depends on the amount of myopia and the ablation zone size. Usually from 3% to 15% of the central corneal tissue is utilized for corneal reshaping for myopic corrections from -1.00 to -6.00.
[An explanation of the size of a micron: The average single human cell is approximately 10 microns in height. The diameter of a single human hair is approximately 50 microns, and the thickness of the central cornea (the front surface of the eye) is a little over 500 microns (half a millimeter). Therefore, only one-tenth of a cell is penetrated by the excimer photons when penetrating one micron.]
Since each photon has energy equivalent to 6.4 electron volts, and the energy required to hold the protein atoms together in corneal tissue is only 3 electron volts, these molecular bonds holding protein molecules together in the cornea are broken, and molecules and atoms of tissue fly away from the cornea, .25 micron layer by .25 micron layer, at supersonic speeds. (This effect is referred to as the "plume of photoablated tissue.") The laser's aperture (mechanical iris) simultaneously expands in a stepped fashion, until the desired optical zone and optical correction are achieved in myopia. Each pulse of 25 billion million photons acts only on those atoms of protein that are bonded together in an area of about 5 or 6 mm or larger, .25 microns in depth, or 1/40th of a single cell. (One cell is only 10 microns.) Each laser pulse lasts approximately 10 nanoseconds, which is 10 billionths of a second, at 10 pulses per second.
Refractive correction is achieved by stepped photoablation in myopia. The Excimer Laser system uses a mechanical iris, or aperture, to control the laser. After each set of laser pulses, the iris diameter widens and the laser ablates, or removes, a slightly larger ring of tissue to effectively flatten the corneal surface, thus creating a stepped curve. In essence, a prescription for glasses or contact lens becomes permanently microetched onto the front surface of the eye.
In most cases it is virtually impossible to detect any change in the cornea several months following surgery, even upon ophthalmic examination through a slit lamp biomicroscope by a well-trained physician. (The only way to detect the change that has occurred in the cornea is with a photokeratoscope.)
Before the Excimer Laser photoablation procedure can be performed, the surgeon must first remove the corneal epithelium (see illustration of cornea). After Excimer Laser photoablation of the cornea, the corneal epithelium will normally regenerate within a period of 48 to 72 hours. Immediately following Excimer Laser photoablation, a pseudomembrane forms, acting as a true osmotic type of barrier to impede water inflow. As soon as the epithelial cells regenerate and cover the area, the cells break down the pseudomembrane and begin to lay down elements of a new basement membrane. Hemidesmosomes anchor the basal epithelial cells down into the basement membrane, locking the newly formed epithelium straight down into the cornea onto the stromal lamellae. Within a period of four to six weeks, the new corneal epithelium stabilizes to the point that to mechanically push the epithelium off the cornea (for instance, by rubbing the eye) would be very difficult.
There is a distinct difference between RK (radial keratotomy) and Excimer Laser PRK (photorefractive keratectomy). RK reshapes the cornea by the surgeon's use of a diamond knife or scalpel to perform multiple deep and relatively wide incisions or cuts (90% corneal depth) into the periphery of the cornea, in a pattern resembling the radial spokes of a wheel, which weakens this area and allows the circumference of the cornea to increase, thus flattening the central cornea. Unfortunately, many people are under the false impression that radial keratotomy (RK) is indeed done with a laser beam. This is not true. Others also mistakenly believe that "laser surgery" reshapes the cornea by making deep incisions or cuts like RK, except that it is done with a laser beam instead of a surgical blade. This also is not true. Excimer Laser PRK and LASIK are considered to be the most technologically advanced methods in the world today for correcting myopia. This advanced technological breakthrough for the correction of myopia allows eye surgery to enter a totally new dimension - a world of its own - never before experienced by eye surgeons.
A summary of the highlights of the development of the Excimer Laser:
Although Excimer Lasers were first developed in 1975, the word EXCIMER, a contraction of the words "EXCIted" and "diMER," appeared in scientific literature as early as 1960. At first, the Excimer Laser was not developed for use in the realm of ophthalmology, but was initially used in 1975 in the plastics industry. The laser was developed for etching silicones and other polymers, and later with the hope of using this technology in manufacturing microcircuits and computer chips.
Excimer Laser surgery is a Western-developed surgical breakthrough. The other, more prevalent form of refractive surgery - Radial Keratotomy, or RK - was developed in the Eastern nations of Russia and Japan. Radial keratotomy, or RK, requires deep incisions or cuts into the cornea with a diamond blade, which changes its shape and structural integrity, in order to correct myopia. The Excimer Laser avoids having to make these deep incisions or cuts into the cornea, and therefore does not weaken the corneal structure. The Excimer Laser photoablates, or uses ultraviolet light energy at a specific wave length to break the cellular bonds of microscopic layers of the cornea in order to change the shape of the cornea to correct myopia or nearsightedness and other refractive errors. The technical term for the Excimer Laser in correcting myopia is Excimer Laser Photorefractive Keratectomy, most often referred to as Excimer Laser PRK.
In 1976, Dr. Dave Muller, Ph.D., formerly President of Summit Technology, Inc., built Cornell University's first Excimer Laser. In 1979 Dr. John Taboada, Ph.D. and colleagues initiated a study of the Excimer Laser on animal eyes at Brooks Air Force Base in San Antonio, Texas. A number of discoveries resulted from these studies, some of which were published in 1980 and 1981. The most intriguing was the observation of a smooth beam-shaped indentation on the cornea of rabbits with experimental Excimer treatment. They attributed the effect to a temperature jump in combination with a photochemical process. Subsequently in 1983, Dr. Taboada and Dr. Steve Trokel, M.D., an Ophthalmologist at Columbia University, met in New York City to complete a co-authored book on YAG Microsurgery. At that time, Dr. Taboada, who is now recognized as the originator of Excimer ablation for refractive surgery, apprised Dr. Trokel on the Excimer Laser process and its application to refractive surgery.
Dr. R. Srinivasan, Ph.D., an I.B.M. researcher in Yorktown, New York, demonstrated the precise photoablation capabilities of the Excimer Laser, which made the Excimer unique among lasers. In late September, 1982, and early 1983, Dr. Srinivasan was using the Excimer Laser for microetching microscopic circuit board technology in computer chips. He described the photoablated decomposition of plastic materials without thermal deformation, as well as decomposition of ultraviolet laser irradiation on biological tissues, such as aorta, bone, cartilage, and hair. He also showed that accurate and smooth microscopic grooves could be microetched on a single human hair with submicron precision without significant surrounding thermal damage to the hair. (A single human hair is approximately 50 microns in diameter.) Dr. Srinivasan microetched, or photoablated, about 30 microns of the human hair. He was impressed as to how sharply defined the edges were and how the microetched hair retained its cylindrical shape. This information was also published, and in 1983, Dr. Steve Trokel, M.D., saw the picture of the microetched hair and visited Dr. Srinivasan at his IBM laboratory in July, 1983. There Dr. Trokel did laboratory studies on rabbit eyes and bovine eyes, and confirmed a significant technological breakthrough. He is regarded as the first ophthalmologist to recognize the significance of the Excimer Laser in corneal refractive surgery.
In 1984, Dr. Olivia Serdarevic, M.D., while at Columbia University (Harkness Eye Institute) in New York, was working with laboratory animals. She was the first to apply the Argon-Fluoride Excimer Laser irradiation to create a therapeutic lamellar keratectomy. In the laboratory she was infecting animal corneas with fungal organisms and was applying the Excimer Laser to the surface of these corneas and was able to sterilize or eliminate the infecting organism. At the same time, she created a therapeutic lamellar keratectomy with a very smooth surface.
From that point on, much research and development began to spring up all over the world, especially in Western nations. The early pioneers include the following: Dr. Steve Trokel, M.D., USA; Dr. Francis L'Esperance, M.D., USA; Prof. John Marshall, Ph.D., England; Dr. Malcolm Ker-Muir, M.D., England; Dr. Theo Seiler, M.D., Ph.D., Germany; Dr. Olivia Serdarevic, M.D., USA; Dr. Carmen Puliafito, M.D., USA; Dr. Roger Steinert, M.D., USA; Dr. Marguerite MacDonald, M.D., USA; Dr. Charles Munnerlyn, USA; and others.
In 1983, Dr. Charles Munnerlyn of the United States started a project which resulted in construction of the first clinical prototype Excimer Laser for ophthalmology. He worked out mathematically the depth of ablation, diameter and edge angles. In 1984, Dr. Marguerite MacDonald from LSU started doing animal research with the Excimer Laser.
Dr. Theo Seiler of Germany ordered his first Excimer Laser in early 1984. In January, 1986, he was the first to create linear and arcuate keratectomies in sighted human eyes for the correction of astigmatism. He performed the first series of phototherapeutic keratectomies (PTK) in sighted human eyes in 1986 in cases of Salzmann's Nodular Degeneration, and for smoothing of the cornea after pterygium removal. On February 6, 1987, Dr. Francis L'Esperance, M.D. of Columbia University, New York, performed the first wide area Argon-Fluoride Excimer Laser superficial keratectomies (PRK) on a series of three human eyes. One of the patients had a malignant melanoma in his eye and was going to have the eye removed. The patient agreed to undergo Excimer Laser surgery prior to the removal of the eye for experimental purposes. This patient had 20/20 vision prior to the Excimer Laser; following the Excimer Laser, the eye was left farsighted, or hyperopic (+3.25 diopters), but was corrected to 20/20 with spectacle correction. In 1988, Professor John Marshall,Ph.D., of England, felt that he had sufficient data from laboratory studies to proceed with human exposure. In March, 1988, the first application of the Summit Excimed UV200 Excimer Laser PTK, or Phototherapeutic Keratectomy, in the U.K. was performed on a sighted human eye for "band keratopathy" (corneal opacity) in London at St. Thomas Hospital by Dr. Malcolm Ker-Muir with great success. In 1988, the United States Food and Drug Administration (FDA) recognized that the experimental research data on laboratory animals was sufficient and satisfactory; therefore, the FDA approved human clinical trials to be started at a number of investigative sites in the United States, approximately 46 sites. In July, 1988, Dr. Marguerite MacDonald, M.D., of LSU, performed Excimer Laser PRK on the first sighted eye with the longest follow-up in the world. In 1989, the first bilateral Excimer Laser PRK for myopia was done in Germany by Dr. Theo Seiler. In 1990, Dr. Howard Gimbel, of Calgary, Canada, began the first Canadian clinical trials for Excimer Laser PRK to correct myopia. On August 5, 1991, the Secretaría de Salud in Mexico City approved Excimer Laser PRK clinical trials to begin. The first Excimer Laser PRK for the correction of myopia in the country of Mexico was performed by Dr. Bobby Maddox, M.D., on January 8, 1992, in Juarez, Mexico. In the United States, the FDA study has completed well over 2,000 cases. The clinical trials that have been going on in Mexico since January, 1992, have been very successful thus far.
Excimer Laser technology has come a long way, and a continual refinement and enhancement of this technological breakthrough is expected as studies progress. The future of the Excimer Laser is going to be exciting to follow. The use of the Excimer Laser in ophthalmology may provide the greatest use of lasers in medicine during this decade and the decades to come. It is expected by most experts that the Excimer Laser will replace radial keratotomy for the most part.
The word EXCIMER is a contraction of the two words EXCIted and diMER. (EXCIted + diMER = EXCIMER). The word DIMER refers to the Argon-Fluoride molecules in the excited state. A dimer is basically a halogen combined with an inert or rare gas in an excited state. A dimer does not exist in the unexcited, or stable, state. The decay of the unstable molecules (Argon-Fluoride) to a stable state results in the emission of a highly energetic photon of ultraviolet light. The emission wavelength of Argon-Fluoride is 193 nanometers. The Excimer Laser is a unique laser in the ultraviolet 193-nanometer region of the electromagnetic spectrum. It differs from other, more commonly used lasers, such as YAG and Argon lasers in several ways.
The Excimer emissions occur in a train of individual pulses, typically 10 nanoseconds long. With a pulse repetition frequency of up to 50 Hertz, each pulse removes, or photoablates, as little as .25 microns of tissue. Remember that one cell is approximately 10 microns in greatest diameter, and one micron is one one-thousandth of a millimeter. Since the beam is unfocused, or parallel, each pulse showers down onto the central deepithelialized cornea about 25 billion million photons in a circular area of approximately 5 mm or more. Since the energy contained in each photon of the Excimer Laser UV light is about twice as strong as the energy holding the corneal protein molecules and atoms together, these molecular bonds are broken and the molecules and atoms of tissue fly away from the cornea, submicron layer by layer, at supersonic speeds. This is referred to as the plume of photoablated tissue. After each set of laser pulses, the mechanical iris, or aperture, in the laser delivery system slowly widens, or dilates, in a stepped fashion, toward the final goal of the selected optical zone size. Thus, the central cornea is flattened, leaving an exquisitely smooth refractive surface, with the microscopic appearance of a Fresnel lens. All of this takes place in about 20 seconds. The depth of the photoablation depends on the amount of myopia present and the selected optical zone size. A specific formula for the calculations was worked out by Dr. Charles Munnerlyn of the United States in the early 1980s.
Munnerlyn's PRK Formula:
Thickness of tissue removed [microns] = (Refractive charge [diopters] /3) x (Diameter of the ablated zone)^2
With a 6.00 mm optical zone and a -1.00 diopter correction, one will need to photoablate approximately 18.25 microns of corneal tissue, or about 3%. For a -6.00 diopter correction, one will need to photoablate 78 microns of corneal tissue. The central cornea, without the epithelium, is approximately 500 microns thick. Therefore, with a -6.00 myopic correction, we only have to photoablate about 15% of the entire central corneal thickness. Of course, if one chooses a larger optical zone size, then more photoablation would be necessary.
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