Refractive Errors and Their Treatment

Figure 1.1 Schematic diagram of emmetropia. In emmetropia, the far point is optical infinity, and the secondary focal point (F2) is at the retina. Parallel rays of light focus on the retina. (From Ref. 115.)

development of LASIK. The argon–fluoride excimer laser is capable of precise ablation of corneal tissue with minimal disruption of adjacent tissue. The excimer laser’s effect on the cornea was first studied in animal models in 1983 (12). In 1989, Peyman first used a laser to remove corneal stroma from a lamellar bed in animals (13). Shortly thereafter, similar attempts were made in human eyes (14,15). This early work supported the theory that in situ keratomileusis was better than surface ablation because it induced less activation and proliferation of stromal keratocytes, thereby avoiding both haze and regression. In addition, the excimer laser allowed for more accurate tissue removal, thereby eliminating one of the main deterrents to lamellar surgery (see Chap. 2).

The LASIK procedure, in its current refined state, involves increasing the eye’s intraocular pressure to at least 65 mmHg with a suction device, and then using a microkeratome to create a corneal flap that is at least 6 mm in diameter and 150 microns thick. This flap, which allows the Bowman’s-layer epithelial complex to remain intact, is then carefully lifted to expose the layers of the cornea that will be reshaped by the excimer laser. The size of the optical zone and the depth and profile of the laser ablation will determine the correction achieved (Fig. 1.1).

B. THE EPIDEMIOLOGY OF LASIK

Refractive surgery is a young and rapidly growing field. In 1998, 400,000 Americans underwent refractive surgical procedures. This represents an increase over 1997 of approximately 100% (16). Despite the many refractive surgeries that have been performed, the target population for laser vision correction at the turn of the century is still an estimated 44 million people. Currently, approximately 3,000 ophthalmologists have been trained to perform refractive surgery. This number is increasing at a rate of 500 to 1,000 surgeons per year. Industry observers predict that the number of trained surgeons will approach 6,000 to 8,000, or approximately 50% of the U.S.-based ophthalmologists (16).

LASIK produces good refractive results for low, moderate, and high myopia (see Chap. 18). Recent reports for low myopia show postoperative uncorrected visual acuities of 20/40 or better in 100% of patients, and 20/20 or better in 81% of patients (17).

Potential complications of LASIK include halos, interface inflammation, haze, and regression. However, significant complications causing a loss of two or more lines of best

corrected visual acuity (BCVA) are rare (1,18,19). In addition, with improved instrumentation and increasing surgeon experience, LASIK complication rates continue to fall.

C. REFRACTIVE ERRORS THAT ARE TREATABLE WITH LASIK

Three components of the eye work together to determine the refractive power of the eye: the shape of the cornea, the power of the lens, and the length of the eye. The overall refracting power of the eye is approximately 60 diopters: the cornea contributes about 45 diopters of power, while the lens provides approximately 15 diopters of refractive power to the eye. When the cornea, lens, and length of the eye combine and produce no refractive error, emmetropia is achieved. In the instance of emmetropia, a ray of light parallel to the optical axis and limited by the pupil focuses at a point on the retina. In other words, the secondary focal point is located on the retina. In addition, the “far point” (i.e., the furthest point at which the eye can see clearly) is optical infinity (Fig. 1.2). Because the cornea accounts for approximately two-thirds of the refractive power of the eye, it is logical that most refractive surgeries attempt to change the shape of the cornea. Other methods of refractive surgery include implanting intraocular lenses.

Traditionally, four major types of naturally occurring ametropias, or refractive errors, have been described: myopia, hyperopia, astigmatism, and presbyopia. Wavefront analysis of human eyes after correction of these optical abnormalities often show additional irregularities that have been classified using Zernike polynomials into complex subgroups that may be simplified into lowerand higher-order aberrations.

In myopia, the secondary focal point is anterior to the retina. In other words, the refractive power of the eye is greater than that required for emmetropia; parallel rays of light entering the eye are in focus at a location in the vitreous, rather than on the retina. Refractive myopia is due to steep corneal curvature or high lens power. Axial myopia is due to an eye that is too long (i.e., longer than 22.6 mm). For every millimeter of axial elongation of the globe, there are 3 diopters of myopia. When myopia is corrected with spectacles, contact lenses, or refractive surgery, the parallel rays of light entering the eye come into focus on the retina, which is consistent with a far point at infinity. The prevalence of physiologic myopia in the general population is approximately 25% (20). LASIK corrects for myopia by removing tissue in the center of the cornea, thereby flattening the cornea and decreasing the refractive power of the eye.

A hyperopic eye’s secondary focal point is posterior to the retina. In other words, parallel rays of light entering the eye come into focus at a location posterior to the retina. Refractive hyperopia is due to a flat cornea (less corneal refracting power), or a lens with lower power. Axial hyperopia is due to a short axial length. While hyperopia affects approximately 40% of the adult population, it is clearly less visually significant than myopia (21). This is because accommodation may produce enough additional plus power to bring the parallel rays of light to focus on the retina. Thus young hyperopes may compensate and see well until their accommodative power weakens and they begin to experience manifest hyperopia in their mid to late 30s. LASIK corrects for hyperopia by removing a ring of tissue around the center of the cornea, thereby making the cornea steeper.

Astigmatism refers to a refractive error in which the curvature of the cornea, or less commonly the curvature of the lens, varies in different meridians. In other words, patients with astigmatism have two focal lines formed by the convergence of rays of light. The first focal line, created by the more powerful corneal meridian, is closer to the cornea. The second focal line, formed by the less powerful meridian, is further away. Dioptrically midway

Figure 1.2 Schematic diagrams of myopia and hyperopia. In myopia, the far point is in front of the eye (top), and the secondary focal point (F2) is anterior to the retina, in the vitreous (middle). In hyperopia (bottom), the rays of light are in focus at a point behind the retina. (From Ref. 115.)

between the two focal lines is the circle of least confusion. A proper refractive correction will place the circle of least confusion on the retina.

While astigmatism is clinically detectable in up to 95% of eyes, astigmatism of less than 0.50 diopters rarely requires optical correction (22). However, 10% of the general population has naturally occurring astigmatism greater than 1 D. Since an astigmatic refractive error of 1.00 to 2.00 D can decrease uncorrected vision to the 20/30 to 20/50 level, this degree of astigmatism causes an unacceptably poor quality of uncorrected visual acuity (23,24).

Regular astigmatism refers to corneal curvatures that are different but symmetrical, with principal meridians 90 degrees away from each other. For regular astigmatism, one

can achieve a refractive correction with cylindrical or spherocylindrical lenses. LASIK can correct regular astigmatism by removing more tissue from the steeper side of the cornea.

Irregular astigmatism refers to a condition in which the principal meridians change from point to point across the pupil, or in which the amount of astigmatism changes from one point to another. Examples of irregular astigmatism include keratoconus or traumatic corneal scars. LASIK is contraindicated in eyes with irregular astigmatism. Often, rigid contact lenses are the best way to improve the visual acuity for eyes with irregular astigmatism. The use of Zernike polynomials to analyze the wavefront in patients with irregular astigmatism has allowed, at least in theory, the incorporation of this information into the laser treatment algorithm in LASIK and paved the way for custom corneal treatments.

Presbyopia refers to the age-related loss of accommodative response. Presbyopia typically sets in at approximately 40 years of age. The condition results from either a loss of lens elasticity or an anatomic change in the position of the lens equator to the ciliary body position. Presbyopia is an important issue to discuss during the informed consent of patients seeking refractive surgery. Some physicians give their patient the option of monovision, in which one eye is corrected for near vision and the other for distance vision.

D. ETIOLOGY, EPIDEMIOLOGY, AND LASIK ALTERNATIVES

1. Corneal Subtractive Procedures

a. Lamellar Procedures

Lamellar refractive keratoplasty refers to the placement of a lenticule on or within the cornea to change its refractive power, typically by altering its anterior curvature. As described above and in Chap. 2, Jose Barraquer’s introduction of lamellar refractive surgery and of cryolathe keratomileusis were followed by Ruiz’ introduction of the concept of in situ keratomileusis (25). He introduced a microkeratome propelled by gears that could create the corneal flap and allow one to perform intrastromal tissue subtraction. When advances in instrumentation allowed the lamellar keratoplasty to be performed more accurately, the procedure became known as automated lamellar keratoplasty (ALK) (Figure 1.3). The initial results of ALK for myopia showed improvement over previous lamellar techniques. Results described postoperative uncorrected visual acuities of 20/40 or better in 86% of patients, with a 6% loss of two or more lines of best spectacle corrected visual acuity (26,27). However, ALK outcomes were not significantly better than the results achieved with contemporary radial keratotomy (RK) techniques (28,29). The accuracy of ALK is limited by the imprecise nature of mechanical cutting.

Hyperopic ALK uses a very deep lamellar pass, cutting more than 70% of the stromal depth (versus the 40% of stromal depth that is used for myopic ALK or for LASIK). The intraocular pressure causes the thinned cornea to bow forward, and thus the central cornea steepens (Figure 1.4). As one may imagine, this procedure was often unpredictable and occasionally led to progressive ectasia. Long-term results published in 1998 reported instability of the postoperative refraction with a progressive myopic shift. Even worse, 26% of eyes developed “iatrogenic keratoconus,” and 16.4% required penetrating keratoplasty (30,31). Hyperopic ALK is now considered unsafe due to the risk of progressive corneal ectasia.

b. Surface Laser Ablation (PRK and LASEK)

Another form of refractive surgery that utilizes corneal subtractive procedures is photorefractive keratectomy (PRK). PRK is more accurate than ALK because it makes use of the

Figure 1.3 Myopic automated lamellar keratoplasty. (A) A microkeratome is used to create a hinged flap in the cornea. (B) A second microkeratome is used to remove a parallel-faced disc of tissue from the corneal bed. (C) The initial flap is replaced, leaving a flattened central cornea. (From Ref. 116.)

193 nm argon fluoride (ArF) excimer laser. Like LASIK, PRK utilizes the excimer laser to flatten the cornea by ablating the central cornea. Unlike LASIK, no corneal flap is made; rather, the central corneal epithelium is simply removed with a spatula or with the laser itself (Fig. 1.5). While there are three distinct techniques for performing excimer laser PRK for myopia, the most widely used technique applies wide-area surface ablation with a largediameter beam. Most of the published results of PRK are based on PRK performed in this manner. It is primarily in Europe that PRK is performed with the two other techniques: scanning slit and flying spot lasers. A modification of PRK, first performed at the Massachusetts Eye and Ear Infirmary by Azar and Abad in 1996, was the use of 20% alcohol to create an epithelial flap which was repositioned to cover the stromal ablation bed. Since then, several investigators have started to use this laser epithelial keratomileusis (LASEK) technique, but it is not clear whether LASEK offers any advantages over PRK.

PRK has been shown to be safe and efficacious for the treatment of low to moderate myopia. Several national studies of PRK demonstrated that 90 to 100% of patients had 20/40 or better uncorrected visual acuity, and 78 to 98% had postoperative refractions within 1.0 D of the target outcome (32–34). Refractive results of PRK in patients with more than 6 D of myopia tend to be highly variable and undergo more regression. Another disadvantage of PRK is a prolonged recovery time: while the corneal epithelium is healing,

thinning, in which less than 200 to 250 microns of tissue would be left in the corneal bed, and epithelial anterior basement membrane dystrophy, because this carries the risk of epithelial ingrowth. PRK is also competitive with LASIK in the arena of treatment for low hyperopia. A recent review of 65 eyes with 1.00 to 4.00 D of hyperopia documented that 92% of the eyes were within 1.00 D of the intended manifest SE at 18 months fol- low-up (44). Other reports support the use of hyperopic PRK (H-PRK) for treating low degrees of hyperopia (45–48). H-PRK for the treatment of higher degrees of hyperopia is less predictable and may result in greater regression (45).

2. Biologic and Synthetic Tissue Addition: Epikeratoplasty and ICRS

One can alter the shape, and thus the refractive index, of the cornea by adding material either to the surface of the cornea or into the corneal stroma. Epikeratoplasty involves adding a lenticule with power (i.e., carved donor tissue) to the deepithelialized surface of Bowman’s layer. Also called epikeratophakia or lamellar keratoplasty, this technique has proven problematical. First, the refractive results have been disappointing: only 33% of eyes achieved 20/40 or better uncorrected visual acuity, 15% lost two or more lines of best corrected visual acuity (BCVA), and regression was more than 2 D in 17.6% of patients at 5 months’ follow-up (49–51). Secondly, 2.5–3.5% of patients who underwent this procedure had delayed reepithelialization, which in some cases led to infections and graft melting (49,52–55). Almost 8% of grafts had to be removed due to failure of epithelialization, haze, glare, irregular astigmatism, epithelial ingrowth, epithelial interface cysts, melt, infection, stromal infiltrates, and wound dehiscence (49,53–54,56–57). After the lenticules were removed, many patients were left with central corneal scarring and loss of BCVA (58,59). Because of the disappointing outcomes and unfortunate complications, epikeratoplasty has been abandoned as a technique for the correction of myopia. However, epikeratoplasty is still occasionally used to diminish the myopia and irregular astigmatism of keratoconus or other corneal thinning disorders (60). This procedure is also sometimes used for the treatment of pediatric and adult aphakia.

Keratophakia is a procedure in which a lens is placed within the corneal stroma to alter the cornea’s refractive power. While lenses used to be fashioned from donor human corneas (homoplastic), these lenses had variable outcomes and a high incidence of complications (61). Keratophakic lenses are now fashioned exclusively from synthetic materials (alloplastic).

The intrastromal corneal ring segment (ICRS), approved in the United States in April 1999, is a keratophakic technique to correct for low myopia ( 1.00 to 3.00 D with an astigmatic component of 1.00 D or less). The ICRS consists of two 160 degree polymethyl methacrylate (PMMA) segments placed in two pockets of the peripheral stroma, thereby inducing peripheral steepening and indirectly causing central corneal flattening (Fig. 1.6). The procedure is unique in that it retains the potential to be adjusted or reversed.

Two-year results of the phase II and phase III FDA trial analyzed 358 patient eyes. At 24 months after surgery, 97% of the eyes had an UCVA of 20/40 or better, 76% were 20/20 or better, and 55% were 20/16 or better. In addition, 93% were within 1.00 D range, and 73% were within 0.50 D range (62).

Potential disadvantages with the procedure include accidental perforation into the anterior chamber, surface perforation of the epithelium anteriorly, and induced astigmatism, which can result from postoperative movement of the intracorneal ring segments (63).

Figure 1.6 Intrastromal corneal ring segments. (From Ref. 63.)

3.Corneal Surface Remodeling: Incisional Surgery, Thermal Surgery, and Orthokeratology

a. Incisional Surgery: Radial Keratotomy

Radial keratotomy (RK) is a procedure that treats myopia by making deep and radial corneal stromal incisions to weaken the peripheral and paracentral cornea and thereby flatten the central cornea (Figs. 1.7 and 1.8). Experimenting on rabbits’ corneas, Dutch ophthalmologist Lendert Jan Lans first demonstrated that nonperforating corneal incisions parallel to the limbus cause peripheral bulging and central flattening (Fig. 1.7) (64,65). Japanese ophthalmologist Tsutomu Sato first performed anterior and posterior keratotomies to treat myopia after observing that patients with keratoconus who had experienced breaks in Descemet’s membrane and hydrops subsequently developed corneal flattening (66–67). Sadly, the role of the corneal endothelium was not understood when Sato was performing his keratotomies. Later follow-up showed that of 170 eyes that underwent a keratotomy by Sato’s group, 121 (71%) developed bullous keratopathy, and only 49 eyes (21%) retained clear corneas. The average time between the procedure and the onset of edema was 20 years (68). The posterior keratotomy was abandoned for anterior keratotomies once the physiological importance of the corneal endothelium had been established.

In 1960, Svyatoslav Fyodorov of the Soviet Union visited Japan, where Akiyama taught him Sato’s technique of radial keratotomy (Sato himself had recently died). Fyodorov improved upon Sato’s techniques by devising improved instrumentation and by developing mathematical formulas to improve the reproducibility of RK (69–70). Fyodorov also showed that paracentral incisions were more effective than peripheral, scleral incisions. In addition, he demonstrated that the diameter of the central clear zone is inversely proportional to the magnitude of refractive correction.

In the United States, the first RK was performed by Bores at the Kresge Eye Institute in November 1978. It was at about this time that the 20 year follow-up data of Sato’s posterior keratotomy patients was revealing the 75% incidence of bullous keratopathy. Because the newer anterior procedure had scarce follow-up data, the National Eye Institute chose to fund two large nationwide studies to examine RK: the Prospective Evaluation of Radial Keratotomy (PERK) and the Analysis of Radial Keratotomy.

Figure 1.7 The development of radial and astigmatic keratotomy. Illustrations of Lans’s studies showing peripheral corneal bulging (A) and subsequent scarring (B) after astigmatic keratotomy (C) and radial keratotomy (D). (From Ref. 117.)

The PERK study showed that 10 years after surgery, 53% of the patients had 20/20 or better uncorrected vision, 85% had 20/40 or better, and 63% of patients younger than 40 years old were spectacle-independent. Low myopes did better than moderate myopes: 94% of patients with low myopia ( 2.00 to 3.12 D) had an uncorrected visual acuity (UCVA) of 20/40 or better, while 79% of moderate myopes ( 3.25 to 4.37) had 20/40 or better UCVA. The 10-year PERK results also revealed a long-term instability of refractive errors:

Figure 1.10 Hexagonal keratotomy. (From Ref. 115.)

In 1989, Jensen and Mendez attempted to improve upon the technique with shorter, nonintersecting hexagonal incisions (84). Despite these modifications, corneal scarring, optical aberrations, irregular astigmatism, perforation after minimal trauma, keratitis, and endophthalmitis were complications that plagued this procedure (85–87). It was soon determined that hexagonal keratotomy was “an unpredictable, unsafe surgical procedure with a high complication rate . . .” (87). As such, the procedure has largely been abandoned.

d. Thermal Surgery

Thermal keratoplasty (TK) was first performed by Lans in 1898 to treat astigmatism (64). Lans applied thermal energy via a cautery to alter the structure of the corneal stromal collagen and change the anterior corneal curvature. Heat was later applied by means of radio frequency waves with instruments like the Los Alamos thermal keratoplasty probe (88). Because it was difficult to control the amount of energy applied, TK using simple cauteries and probes resulted in unpredictable results and regression (89,90).

Interest in TK was rekindled with the introduction of lasers that could heat the cornea in a more controlled manner. In 1990, Seiler first reported the use of the holmium:yttrium aluminum garnet (Ho:YAG) laser for hyperopia, a technique called laser thermokeratoplasty (LTK) (91). Ho:YAG LTK delivers infrared radiation that is focused on the midstroma, thereby avoiding damage to the epithelium. Two types of Ho:YAG LTK delivery systems were developed: contact and noncontact.

Contact LTK was performed by applanating the cornea with a probe that applied energy pulses to achieve local, peripheral flattening and subsequent central steepening. In the early 1990s, the procedure underwent Food and Drug Administration (FDA) trials. Regression and undercorrection plagued the procedure, and contact LTK was withdrawn from US FDA trials (92).

Noncontact LTK is performed by projecting simultaneously up to eight spots onto the cornea through a slit lamp-mounted fiberoptic delivery system. FDA phase Iia clinical trials with two years of follow-up showed a mean change in refraction of 0.53 to1.48 D, with UCVA at two years improved by one or more lines of Snellen visual acuity in 19 (73%) of 26 treated eyes (93). The problem with noncontact LTK is regression. Studies have shown 31.5 to 40% regression (94,95). Another problem apparent with LTK is the induction of irregular astigmatism (95,96). Despite these imperfections, noncontact

Ho:YAG LTK recently received approval by the FDA. Some investigators are attempting to improve upon the current pulsed Ho:YAG LTK with a new continuous wave diode laser that can achieve similar effects on the cornea, without the peaks and troughs of the pulsed laser (97).

e. Orthokeratology

Orthokeratology is the programmed application of contact lenses to reduce or eliminate refractive anomalies, primarily myopia. An orthokeratology lens is flatter, looser, and larger than a conventional lens. Theoretically, the lens mechanically alters the central corneal contour over time. In 1963, Grant and May introduced this practice to the United States. They fitted a rigid PMMA lens that was 0.37 diopters flatter than the patients’ flattest corneal median. As the cornea flattened, new lenses were applied, each time 0.37 D flatter than the flattest meridian. The patients wore their lenses for 12 to 15 hours a day and were followed at regular intervals. During the first phase of treatment, the adaptive phase, an average of six pairs of lenses was prescribed over a period of 18 to 24 months. When unaided vision reached 20/20 or refraction stabilized to plano 0.50 diopters, the retainer phase began and patients would then wear a retainer lens to maintain the permanence of the procedure (98,99).

While many anecdotal reports describe the myopia-reducing benefits of orthokeratology, there are no scientific studies to support claims that this practice is a viable alternative to refractive surgery. For example, one randomized, controlled clinical trial did demonstrate an improvement in uncorrected visual acuity from 20/100 to 20/50 in 36.6% of the orthokeratology group compared with 20.8% of the cosmetic lens wearers who improved the same amount. However this trial had no long-term follow up; results were from data at the very end of the 14 month (on average) treatment period (100).

4. Altered Index of Refraction: Phakic IOLs

Most types of refractive surgeries alter the cornea; however, the refractive power of the eye can also be adjusted by implanting an intraocular lens (IOL), with or without extraction of the crystalline lens. Barraquer implanted the first phakic intraocular lens in the 1950s (101). Unfortunately, many of these anterior chamber lenses were poorly finished and had sharp edges. After Barraquer implanted almost 500 lenses, significant complications such as corneal edema occurred, and over 300 of the lenses had to be removed (102). Because of experiences like this, interest in phakic IOLS waned until the labs were better able to guarantee the quality of IOLs.

Modern IOLs are of much better quality than those used in the 1950s. A recent study used a scanning electron microscope to analyze the surface quality of new generation phakic IOLs; the study showed that these lenses did not have any defects that would contraindicate their use as phakic IOLs (103). This study examined the three major types of lenses used as phakic IOLs today: anterior chamber lenses, iris-fixated anterior chamber lenses, and posterior chamber lenses (Fig. 1.11). Even in IOLs with smooth surfaces, however, there is still a risk of progressive corneal endothelial cell loss with the use of phakic IOLs (104–108). Other complications include cataract formation, endopthalmitis, and retinal detachments (109–112).

While phakic IOL implantation does have risks, this procedure enjoys many advantages for the correction of refractive errors: the procedure is both highly predictable and re-

versible, it can correct higher refractive errors than LASIK and other types of refractive surgeries, and it can be performed by most ophthalmologists. In addition, phakic IOLs, while currently used to treat myopia, may soon be approved to correct hyperopia. A recent Phase I trial of silicone plate posterior chamber lenses, implanted in hyperopes, reported 100% of patients with 20/40 or better UCVA, and 70% with 20/20 or better UCVA (113).

The field of refractive surgery has changed significantly since Sato introduced radial keratotomy and Barraquer performed his first cryolathe keratomileusis. Advances in instrumentation, and in research and understanding of the eye and wound healing, and constant surgical innovation, will surely keep the field changing and improving as the years progress.

In the twenty-first century, LASIK has crossed the genre from medical procedure to star-endorsed “miracle treatment.” The public is familiar with the litany of celebrities who have had success with the procedure. When a sports celebrity or an eye surgeon is willing to bet with such high stakes, perhaps the general public feels more comfortable taking a risk as well. More than one million Americans have had LASIK procedures, and predictions estimate that 1.2 million Americans will undergo LASIK in the year 2001 (2).

Some decry LASIK as a shift from disease-driven to demand-driven procedures. There are, however, individuals (such as athletes, firefighters, and military personnel) for whom spectacles or contact lenses are hindering or even dangerous. In addition, people with a high degree of myopia may find glasses to be inadequate due to image minification, or they may be intolerant of contact lenses. The visual disability of high myopes can reduce their quality of life so much that some studies suggest that refractive surgery for high myopes should be provided under health plans like Great Britain’s National Health Service.

Figure 1.11 Phakic IOLs. Drawings illustrating the three major types of phakic intraocular lenses in use today. (From Ref. 119.)

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