Excimer Laser Photorefractive in High Myopia A Multicenter

Keratectomy

Study

Neal A. Sher, MD; Mark Barak, MD; Sheraz Daya, MD; Janet DeMarchi, COT; Angela Tucci; David R. Hardten, MD; Jonathan M. Frantz, MD; Richard A. Eiferman, MD; Paula Parker, COMT; William B. Telfair III, PhD; Stephen S. Lane, MD; Richard L. Lindstrom, MD \s=b\ Excimer photorefractive keratectomy was performed at three centers on 16 highly myopic eyes (8 diopters [D] or more) and followed up for 6 months. Ablation depths ranged from 137 to 230 \g=m\m. The preoperative spherical equivalent of myopia ranged from \m=-\8.62D to \m=-\14.50D (mean\m=+-\SD,\m=-\11.57\m=+-\1.62 D). Six months after surgery, the mean refraction (spherical equivalent) was \m=-\0.90\m=+-\2.1 D. Eleven of 16 eyes achieved refractions within 2 D of that attempted. All eight patients at one site were treated with a maximum-beam diameter of 6.0 mm and were corrected to within 2 D of that attempted, and all were 20/40 or better uncorrected. Three of eight eyes at the other two sites were treated with a 5.5- or 5.6-mm maximum-beam diameter, which achieved corrections within 2 D of that attempted. The epithelium healed within 3 to 4 days, and there were no erosions. Mild subepithelial reticular haze, similar to that seen with excimer photorefractive keratectomy for lower myopia, was seen in all patients, with two patients experiencing more significant corneal haze. This peaked at 3 to 6 weeks and then gradually diminished. All but two patients had a return of their best corrected preoperative visual acuity to within one Snellen line at 6 months. This preliminary study shows excimer photorefractive keratectomy to be a promising surgical treatment for patients with higher myopia.

(Arch Ophthalmol. 1992;110:935-943)

^T^he

193-nm excimer laser has

generated great inpotential to eliminate myopia in a brief surgical procedure using topical anesthesia. Most early published studies of this new technology were limited to eyes with myopia of less than 8 diop¬ ters (D).1'2 It was thought that the deeper ablations -*-

terest due to its

Accepted for publication April 22, 1992. From the Excimer Research Group, Phillips Eye Institute, Minneapolis, Minn, and the Department of Ophthalmology, University of Minnesota Medical School, Minneapolis (Drs Sher, Barak, Daya,

needed for larger corrections would result in increased corneal haze. More recent reports by Seiler and Wollensak3 and Gartry et al,4 using the Summit UV-200 la¬ ser (Summit Technologies, Watertown, Mass) and Mc¬ Donald et al2 using the VISX Model Twenty Twenty laser (VISX Co, Sunnyvale, Calif), reported unpredict¬ able results in attempted corrections over 7 D. This has led investigators to limit attempted corrections to 8 D. The newer protocols from the US Food and Drug Ad¬ ministration (FDA) limits the Phase-Ill photorefrac¬ tive keratectomy (PRK) trials to corrections between -1.0 and -6.0 D. Our early experience with higher myopic corrections has been more favorable. In 1990, we reported our ear¬ liest cases of excimer PRK in a phase-II study using a 5.0-mm-diameter ablation zone and a heavy regimen of topical corticosteroids on seven sighted eyes with my¬ opia ranging from -5.5 to -12.0 D.5 We found near total correction of myopia in these initial patients and min¬ imal regression at 2 years. Our group subsequently per¬ formed a phase-IIA series of 31 eyes with encouraging results on patients with myopia between -4.5 and -8.0 D.6 Our experience with phototherapeutic keratectomy for scar removal also found that deeper ablations of up to 220 µ did not induce an unacceptable level of corneal haze.7 This initial success encouraged our groups and the VISX Company to obtain FDA permission to per¬ form excimer PRK on a small series of patients with very high myopia. We report herein the results of ex¬ cimer PRK performed on a series of 16 highly myopic eyes ranging from -8.62 to -14.50 D. PATIENTS AND METHODS Patient Selection

and

Hardten, Lane, Lindstrom, and Mss DeMarchi and Parker); the Eye Center of Florida, Fort Myers (Dr Frantz); the Department of Ophthalmology, University of Louisville, Ky, and Veterans Affairs Medical Center, Louisville (Dr Eiferman); and VISX Co, Sunnyvale, Calif (Dr Telfair and Ms Tucci). Dr Sher owns stock in VISX Co (purchased on the open market), and Dr Telfair and Ms Tucci are employees of the VISX Co. The other authors have no financial interest in VISX Co or in any products mentioned in this article. Presented in part at the American Society for Cataract and Refractive Surgery, San Diego, Calif, April 14, 1992, and at the Association for Research in Vision and Ophthalmology, Sarasota, Fla, May 4, 1992. Reprint requests to Phillips Eye Institute, 2215 Park Ave S, Minneapolis, MN 55404 (Dr Sher).

Patient selection met FDA8 criteria under an Investigational Device Exemption for this phase-IIA study. Patients were at least 18 years old and had myopia between -8.62 and -14.50 D (spherical equivalent) and best corrected visual acuity of 20/60 or better. Due to anisometropia after excimer PRK, the ability to successfully wear a contact lens was a prerequisite. Patients with abnormal corneas, severe dry eyes, blepharitis, or lagophthalmos were excluded. Preoper¬ ative and postoperative corneal topography at 1, 3, and 6 months was performed using the Computed Anatomy Sys¬ tem

(Minnesota cases; Tomey Technology Co, Cambridge,

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Table 1.—Patient Patient 1

10 12 13 14 15 16

Site

Minneapolis, Minn Minneapolis Minneapolis Minneapolis Minneapolis Minneapolis Minneapolis Minneapolis Louisville, Ky Louisville Louisville Louisville Fort Myers, Fla Fort Myers Fort Fort

Myers Myers

Age,

y

Sex

74

53 34 47 42 34 21 42 34 27 27 37 22 49 31 66

Mass), the Eyesys System (Kentucky cases; Eyesys Labs, Houston, Tex) or with an integrated digital keratoscope

within the laser. If subclinical keratoconus was suggested by corneal topography, the patient was excluded from treat¬ ment. Only one eye from each patient was treated. All patients included in the protocol and followed up for at least 6 months were included. There were no cases unavailable for follow-up. Patient data are summarized in Table 1. Instrumentation

The laser used in Minneapolis (Minn) and Fort Myers (Fla) was the VISX Model L V 2015 (VISX Co, Sunnyvale, Calif). The laser used in Louisville (Ky) was a modified VISX Model LV 2000, which had identical laser cavity and output variables as the LV 2015. These lasers were originally manufactured by Taunton Technologies (Monroe, Conn), which has merged with VISX Company; the laser has been fully described by L'Espérance et al9·10 and by our group.57 It used an argonfluoride gas mixture to produce a 193-nm wavelength at 10 Hz and was adjusted to deliver a fluence of 100 to 120 mJ/cm2. The entire laser system has a computer control module with an in¬ teractive menu, real time monitoring of procedure parameters, and an integrated digital keratoscope. The laser was calibrated before and after each treatment session by ablating standard¬ ized plastic discs and measuring ablation depths with a special micrometer gauge. The desired dioptric change was entered into the computer control console. The maximum-beam diam¬ eter was 5.5, 5.6, or 6.0 mm depending on the site. A suction device placed within 1 cm of the cornea was used to remove par¬ ticles in the ejection plume.

Preoperative and Postoperative

Examination

All patients underwent complete ophthalmologic examina¬ tions including slit-lamp photography, topographic analysis, and ultrasonic pachometry, the details of which have been fully described elsewhere.57 Contrast sensitivity was tested in Minnesota by forced choice testing using the MCT 8000 (Vistech Consultants, Dayton, Ohio). Standardized lighting under the day vision protocol was used in all testing. Testing was performed at five spatial frequencies from 1.5 cycles per degree to 18 cycles per degree. The paired Student t test was used to compare the values at each frequency to determine statistical significance. Separate subjective evaluations of corneal haze were made for the epithelium (superficial, deep) and the stroma (ante¬ rior, posterior) using a qualitative scale (0 to 5). A rating of

Population Data Surgery

Date 7/10/91 6/26/91 7/8/91 7/24/91 7/31/91 7/24/91 7/29/91 8/22/91 9/4/91 9/4/91 9/11/91 9/25/91 6/28/91 6/28/91 7/12/91 8/21/91

Ablation Depth, µ 137 223 172 223 199 223 223 230 170

Treatment Diameter,

153 180

146 149 180 178 164

mm

6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0 5.6 5.6 5.6 5.6 5.5 5.5 5.5 5.5

0 indicated a clear cornea; 0.5, barely detectable haze; 1.0, mild haze probably not affecting vision; and 2.0, moderate haze probably affecting vision. Objective documentation of haze was provided with standardized slit-lamp photography, including tangential broad beam, thin slit at 45°, broad beam at 45°, and diffuse views. The above testing was repeated at 3, 6, 12, and 24 weeks. All refractions, manifest and cycloplegic, were done by one clinical coordinator at each center at similar levels of illumination with notation of pupil size.

Surgical

Procedure

The same surgical technique was performed at all sites. All experience with PRK and have been involved in the trials since 1989. The vi¬ sual axis was marked, with the patient fixating on an inter¬ nal fixation target coaxial with the surgeons fixating the eye and marking the patient's cornea over the center of the en¬ trance pupil, as suggested by Uozato and Guyton.11 A 6.0- or 7.0-mm corneal marker, premarked with blue dye, was cen¬ tered on the epithelial impression made by the Sinskey hook and was then used to mark the epithelium, which was then gently removed using a Tooke knife. Visualizing the patient's eye through the microscope and video monitors, the surgeon aligned the corneal apex to the laser plane by adjusting table travel in the X, Y, and directions. The eye was sometimes fixated with a forceps. Laser energy was delivered in a series of pulses, predetermined through a rotating series of 15 ap¬ ertures of diminishing size. The duration of the actual laser emission was 45 to 90 seconds. surgeons at each site have had extensive

Postoperative Regimen

Following the ablation, tobramycin dexamethasone suspen¬ sion drops (Tobradex, Alcon, Fort Worth, Tex) and 5% homatropine hydrobromide (Alcon) were instilled and the eye had a disposable soft contact lens (Vistakon Acuvue, Johnson & Johnson, Claremont, Calif) placed or, in several instances,

patched overnight.

In some cases, the contact lens was continued for the first 3 weeks to promote epithelial growth. The next day the pa¬ tient began receiving on 0.1% fluoromethalone (FML, Allergan Co, Irvine, Calif) every 2 hours for the first week, four times per day for the first month, three times per day for the second month, and gradually tapered over the next 2 to 3 months. A 0.3% solution of tobramycin (Tobrex, Alcon) was administered four times per day until the epithelium was healed.

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Fig 1.—The change in refraction (spherical equivalent) after photorefractive keratectomy (PRK) for each patient at 6, 12,

and 24 weeks at each site. The dotted lines represent ±2 D from emmetropia.

Statistical comparisons were made using the Student t test. All values are presented as means ±SDs. The results will be presented according to guidelines for presenting refractive surgical data as suggested by Waring.12 RESULTS Patient Data

operations performed at the three sites, which were followed up for 6 months, were included. Patient 1 was also included but underwent a phototherapeutic keratectomy protocol for anisometropia. This 74-yearold man had undergone prior extracapsular cataract surgery and intraocular lens (IOL) implantation and had anisometropia of approximately 9 D. He was All

unable to wear a contact lens due to arthritis. The re¬ mainder of the patients did not have any prior corneal or intraocular surgery. Sixteen eyes of seven male and nine female patients ranging in age from 21 to 74 years were treated. The location, age, date of treatment, ab¬ lation depth, and maximum ablation diameter are listed in Table 1. All patients underwent epithelialization by 4 days after surgery. It was our clinical impression that the newly healed corneal surface took longer to become smooth than in ablations of lower dioptic corrections. There were no instances of recurrent corneal erosions.

Refractive Data

Table 2 lists the manifest refraction, average keratometry, corneal haze scale values, and corrected and uncorrected visual acuities for each patient at 6 and 12

weeks and 6 months after surgery. The mean pre¬ operative spherical equivalent of refraction was —11.59±1.62 D. The mean postoperative refraction was 1.04± 1.71 at 6 weeks, -0.55±2.37 at 12 weeks, and -0.90±2.13 at 6 months. Figure 1, top left, shows the individual refractive change over time at Minnesota and Fig 1, bottom, shows the changes over time at Kentucky and Florida. Figure 2 shows the attempted vs achieved correction at 6 months at all three sites. At Minnesota, all eight eyes achieved correction within 2 D of that attempted, at Florida three of four eyes achieved similar results, and at Kentucky one of four eyes had similar success. Overall, at the 6-month visit, 11 (69%) of 16 were corrected within 2 D of that attempted. All eyes except two achieved their best corrected preoperative vision within one Snellen line. Patient 14 experienced loss of vision to a best corrected acuity of 20/50. Patient 9 had undercorrection and sig¬ nificant epithelial hyperplasia.

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Fig

(spherical equivalent)

Fig 3.—The mean (±SD) keratometry before and at 6, 12, and 24 weeks after photorefractive keratectomy (PRK).

Fig 4.—The mean (±SD) central ultrasonic pachometry before and at 6, 12, and 24 weeks after photorefractive keratectomy (PRK).

Fig 5.—The mean (±SD) corneal haze readings for the epithelium and the stroma before and at 6, 12, and 24 weeks after photorefrac¬ tive keratectomy (PRK).

2.—The

attempted vs

achieved refraction

at 6 months for the three sites.

Astigmatism There was

no

postoperative

significant change in preoperative and cylinder at 6 months (two-

refractive

sided t test). Mean keratometry values, measured before surgery and at various postoperative intervals, are shown in Fig 3. The mean preoperative keratometric finding was 45.39 ±1.61 D and the mean postoperative values at 6 months were 39.25±2.61 D, showing considerable cor¬ neal flattening. Pachometry values at these intervals are plotted in Fig 4. It shows a mean value of 542 ±39 µ before sur¬ gery and 450 ±48 µ 24 weeks after surgery. Corneal Haze

Corneal haze scores are listed in Table 2 and sum¬ marized in Fig 5. The mean haze scores over time for the epithelium and stroma are shown. The highest scores observed in the epithelium or stroma for an in¬ dividual patient are presented in Table 2 and were used

to compute the mean values. At 6 months, corneal clar¬ ity readings of 1.5 or less were seen in all but four cases (9,11,12, and 14). Patients 9,11, and 12 had a haze rat¬ ing of 2 and all experienced some undercorrection. None of these three patients experienced a significant

loss of best corrected vision. Patient 14 also had a stre¬ mai haze rating of 2 and an initial overcorrection that regressed. This patient sustained a loss of best cor¬ rected vision from 20/20 to 20/50+2 at 6 months. This improved to 20/25, 9 months after surgery; however, the corneal haze remained at a rating of "2." In most cases, the haze peaked at 6 to 12 weeks and then diminished slightly. A fine reticulation noted at the stromal interface was seen in all patients. Some of these reticulations were almost confluent. Otherwise, the changes were similar to those described in our case re¬ ports in more detail.57 Contrast

Sensitivity

Contrast sensitivity before and after surgery for six of the eight Minneapolis patients in whom these data were

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Table 2.—Refractive Data* Patient No.

Visit

Preop 6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk

12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 6 wk

12 wk 6 mo

Preop 10

6 wk 12 wk 6 mo

Preop 6 wk 12 wk 6 mo

Preop 12

6 wk 12 wk 6 mo

Preop 13

6 wk 12 wk 6 mo

Preop 14

6 wk 12 wk 6 mo

Preop 15

6 wk 12 wk

6 mo

Preop 16

6 wk 12 wk 6 mo

*VA indicates visual

Manifest Refraction -9.25+1.25 X165 + 1.50+1.25 X95 +2.00+0.75 X155 0.00 +0.50 x80 -16.50+3.00 X15 -2.25+1.00 X170 -0.75+1.25 X145 +1.25 sphere -10.75+0.75 X70 -2.25+1.00 X170 -0.75+1.50 X95 -0.50+1.50 X95 -12.00+1.25 X80 +0.25+1.25 x80 +0.25+1.25 80 0.00+1.25 X75 -12.00+0.75 X85 +1.25+0.75 X80 +0.50 +0.25 X85 -1.00+1.25 X75 -14.50+1.00 X165 +0.75+2.25 X110 +0.50+2.50 X110 0.00+1.50 X115 -13.25+1.25 X125 +0.25+3.50 X10 -0.50+2.00 X165 1-1.00+1.00 X180 -14.50+0.50 X90 +0.25+1.50 X70 -1.00+1.75 X75 -1.50+0.75 X65 -12.25+1.50 X105 -2.00+1.00 X135 -3.50+1.75 X90 -4.25+1.75 X105 -10.25 sphere -2.25 sphere -5.00 sphere -4.50 sphere -12.25+1.00 X55 0.00 +0.50 X95 -3.00+0.75 X90 -4.00+0.50 X100 -10.50+1.00 X60 -2.25+0.25 X105 -1.00+0.75 X105 -3.75+1.00 x65 10.25 sphere + 1.00+2.50 X20 -6.00 +0.50 X30 -4.25+0.75 X15 -12.00 sphere +3.75 +2.25 X68 + 1.00 +2.00X70 +0.50+2.50 X150 -12.75+1.50 X106 1-1.00 sphere -0.25 +0.50 X126 -1.00+0.50 X105 -11.00 sphere -0.50+1.75 X88 -0.75 +2.00 X76 -1.00+2.25 X76

acuity; preop, preoperative;

and

Average Keratometry, 43.37 36.25 37.00 35.75 45.25 37.87 37.12 37.00 45.25 36.75 37.50 38.75 46.63 37.00 37.00 38.12 47.50 39.50 39.43 40.43 45.50 35.87 36.38 36.63 47.12 40.50 40.75 36.75 45.75 37.87 38.37 37.87 44.00 40.12 40.50 40.75 42.50 42.62 42.62 47.00 40.00 42.68 42.25 48.37 42.25 42.87 45.00 44.87 40.12 42.50 41.94 43.87 36.00 42.31 38.25 44.12 37.75 38.75 38.25 45.12 37.00 38.37 37.62

D

Corneal Haze 0.0 0.5 0.5 0.5 0.0 1.0 1.0 0.5 0.0 0.5 0.0 0.0 0.0 1.0 1.0 1.0 0.0 1.5 0.5 0.5 0.0 0.5 0.5 0.0 0.0 1.5 1.0 1.0 0.0 1.5 0.5 1.0 0.0 1.0 1.0 2.0 0.0 1.0 1.5 1.5 0.0 1.0 2.0 2.0 0.0 1.0 1.5 2.0 0.0 1.0 0.5 1.0 0.0 1.0 2.0 2.0 0.0 1.0 1.0 1.0 0.0 0.5 0.0 0.0

CF, counting fingers.

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Best Corrected VA 20/30 20/25 20/40 20/25 20/40 20/40 20/40 20/30 20/30 20/25 20/25 20/25 20/40 20/20 20/20 20/20 20/20 20/25 20/20 20/25 20/20 20/20 20/20 20/25 20/50 20/30 20/30 20/20 20/25 20/25 20/20 20/20 20/25 20/25 20/20 20/20 20/20 20/20 20/20 20/20 20/25 20/25 20/25 20/20 20/30 20/20 20/20 20/15 20/30 20/20 20/20 20/20 20/25 20/50 20/50 20/25 20/30 20/30 20/30 20/20 20/30 20/30 20/30

Uncorrected VA CF 20/100 20/40 20/30 CF 20/80 20/50 20/40 CF 20/30 20/30 20/25 CF 20/40 20/40 20/20 CF 20/50 20/40 20/25 CF 20/40 20/30 20/40 CF 20/60 20/80 20/30 CF 20/40 20/40 20/30 CF 20/50 20/60 20/200 CF 20/60 20/400 CF CF 20/25 20/50 20/200 CF 20/40 20/50 20/80 CF 20/30 20/400 20/200 CF 20/200 20/100 20/70 CF 20/30 20/30 20/30 CF 20/70 20/70 20/80

Fig 6.—Patient 8. Top left, Normalized corneal topographic map for the left eye before excimer photorefractive keratectomy (PRK). Top right, Normalized corneal topographic map for the left eye 1 month after PRK. The area of maximal flattening is slightly decentered superonasally. Bottom left, Normalized corneal topographic map for the left eye 6 months after PRK. Bottom right, Normalized corneal topographic map for the change in topography from before to 6 months after PRK. White shows the area of maximal decrease in corneal curvature. available was compared. The contrast sensitivity did not vary statistically at any frequency 6 months after sur¬ gery. Corneal

Topography

The topographic maps for patient 8 are shown in Fig 6. The preoperative pattern was typical for myopia with a small degree of astigmatism (Fig 6, top left). Power within 2 mm of fixation varies from 44.93 to 46.54 D. The surface asymmetry index, which is a measure of the surface asymmetry, was 0.27. In the 1-month post¬ operative topographic map, the power within 2 mm of fixation varied from 32.09 to 39.45 D (Fig 6, top right). The flattest portion of the cornea is 1.2 mm away from the point of fixation. The surface asymmetry index was 1.71. Six months after excimer laser photorefractive keratectomy, the power within 2 mm of fixation varied from 35.60 to 40.31 D (Fig 6, bottom left). The flattest portion of the cornea is 0.5 mm away from the point of fixation. The surface asymmetry index has now de¬ creased to 0.47. Figure 6, bottom right, graphically shows the difference between the preoperative and 6-month topographies. There is a well-centered area of maximal change as shown by the white areas.

Intraocular Effects

There were no intraocular effects seen in any eye. There were no patients with increases in intraocular pressures over 22 mm Hg.

Subjective Patient Responses The patients in Minneapolis were given a preopera¬ tive and a 6-month postoperative questionnaire. Five of eight patients described starburst or halos at night. No patient complained of fluctuations of vision or foreignbody sensations. When asked to rate their satisfaction on a numerical scale of 1 (least satisfied) to 10 (most satisfied), the mean response was 9.21. When asked to rate their experience with their expectations, the mean rating was 7.36 (5.0 being expected). All seven eligible patients desired to undergo PRK on the second eye. COMMENT

Refractive correction of high myopia is a difficult clinical problem. Spectacles are thick and produce minification of images, aberrations, and limitations in the visual field as well as poor cosmetic appearance. Contact lenses offer better visual results than do spec-

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Table

3.—Relationship

Between Desired Refractive

Change,

the Diameter of the Ablation Zone, and the

Ablation Refractive Change, D -6.00 -7.00 -8.00 -9.00 -10.00 -11.00 -12.00 -13.00 -14.00 -15.00

4.0

mm

48 56 64 72 80 88 96 104 112 120

4.5

mm

60 70 80 90 100 110 120 130 140 150

5.0

mm

72 84 96 108 120 132 144 156 168 180

facies, but a number of patients cannot tolerate these lenses. At this time, there is no satisfactory surgical procedure for the correction of high myopia. The upper

limit of correction that can be achieved with radial keratotomy is generally thought to be 8 D.13 Myopic epikeratophakia with frozen lyophilized tissue has not proven to be accurate1415 and myopic lenticules are no longer available commercially in the United States. Onlay grafts or fresh tissue epikeratophakia and keratomileusis have had more satisfactory results but require special equipment and surgical skills.1" Intracorneal lenses, made either of polysulfone or hydrogel, have not yet proven practical due to interface problems and subluxations17 or undercorrection.18 Clear lens ex¬ traction and low-power IOLs have not gained wide ac¬ ceptance due to complications including retinal detach¬ ment.19 Phakic IOLs have generated renewed interest in recent years, especially in Europe, but recent stud¬ ies of semiflexible anterior chamber IOLs show greater than 20% endothelial cell loss in 36% of the eyes.20 In another study of iris-fixated IOLs, significant compli¬ cations including uveitis, wound leak, glaucoma, and corneal decompensation were reported.21 These studies should be a warning to ophthalmologists to be ex¬ tremely cautious with this surgical approach. Excimer PRK has generated high expectations among ophthalmologists for the correction of low and possibly moderate myopia. Current phase-Ill PRK protocols in the United States are restricted to correc¬ tions up to 6 D. These restrictions were based on dis¬ appointing results in the treatment of higher myopia. In a preliminary series of patients undergoing excimer PRK, McDonald et al2 reported significant regressions by 3 months in a subgroup of patients with myopia be¬ tween 5 and 9 D. Ablation diameters of 4.25 to 4.50 mm were used. They postulated that the ablation diameters were too small, leading to a shape of the stroma cut that was "too steep and deep" in shape, causing chemical mediators in the stroma to heal the ablation as if it were an incision. Gartry et al,4 using the Summit machine and a maximum-beam diameter of 4.0 mm, reported similar unpredictable results in a series of eyes with a mean myopia of —10 D attempting corrections of 7 D. These eyes showed marked regression of effect after an initial overcorrection. This regression was evident af-

Depth by Diameter, 5.5

µ

of Ablation

m

6.0 mm 108 126 144 162 180 198

mm

90 105 120 135 150 165 180 195 210 225

Depth

216 _

234 252 270

6.5 mm 126 147 168 189 210 231 252 273 294 315

7.0 mm 150 175 200 225 250 275 300 325 350 375

ter the eighth week and stabilized by 6 months after surgery. Sedaravic and associates22 in Italy have reported limited success in a series of 40 patients with myopia ranging from 10 to 22 D. Using the Aesculap-Meditec excimer laser (Carson [Nev] Laser Ine, US distributor) and a relatively high fluence of 250 mJ/cm2, they per¬ formed ablations of 170 to 220 µ with a scanning 7xl-mm slit ablating a 5.5-mm diameter. Regressions of 2 to 6 D were common and sometimes larger regres¬ sions were seen in the more myopic eyes. At least 25%

of patients had significant corneal haze that was related to the depth of the ablation and delays in reepithelialization. Brancato and a multi-user group of investiga¬ tors,23 also in Italy, using the Summit machine and an ablation zone of 3.5 to 4.8 mm, recently reported prom¬ ising results in a large series of eyes including 14 eyes with myopia greater than 10 D followed up for 6 months. The mean difference between attempted and achieved correction was -1.5 D; however, individual case outcomes were not presented. They found more regression in the eyes with higher myopia and also found that the greater the ablation zone diameter, the less the haze that was present. Another approach to excimer PRK in high myopia is the use of a multizone technique that has the advantage of reducing the ablated amount of corneal tissue by 30% to 40%. Dossi24 and associates used a 6.0-mm optical zone for an initial correction followed by an ablation in a 5-mm zone. Initial results were promising and further data will be published this year (F. Dossi, written communication, February 1992). In December 1991, a similar protocol was be¬ gun in the United States using the VISX Twenty Twenty machine and three zones. In this protocol, 20% of correction is done at 6 mm, 30% at 5 mm, and 50% at 4 mm. To date, 12 patients have been treated, and definitive data is not available. To avoid the regressions seen by the other investi¬ gators, we used a larger ablation diameter of 5.5 mm to 6.0 mm, which necessitated deeper ablation depths. The goal was to create a larger transition zone at the periphery of the ablated area. The ablations were car¬ ried out at a relatively low fluence of 120 mJ/cm2. It is hoped that this will not stimulate to the same degree

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keratocyte activation and active stromal remodel¬ that causes regression and haze. ing The reasons for the site-to-site variation in results in this study are not understood. All operations were performed by experienced surgeons with the same technique. Although the number of cases is not suffi¬ cient to draw definite conclusions, the use of the larger 6.0-mm beam diameter may be one factor. Operations performed more recently at Kentucky and Florida us¬ ing a 6.0- to 6.2-mm beam diameter showed improved results similar to those obtained in Minnesota, although 6-month follow-up is not yet available (R.A.E., J.M.F., unpublished data, 1992). (Individual machine calibra¬ tion problems are always a possibility. In an earlier study, we described the effects of lower-than-desired fluence due to calibration problems resulting in undercorrections.7 When a series of undercorrections or overcorrections occur in the same treatment session, laser calibration or some other mechanical malfunction should be suspected.) Another advantage of the larger ablation zone is that it would diminish the importance of errors in centration that have been shown to occur in some PRK proce¬ dures.25 The relationship between beam diameter, depth of ablation, and refractive change was first described by Munnerlyn et al26 and slightly modified for this study. Table 3 summarizes these relationships. We avoided ablations over 250 µ and are concerned about the potential effects of these deeper ablations on cor¬ neal integrity over the long term. Experimental stud¬ ies27 on deep excimer laser ablations in human cadaver eyes have raised concerns about paradoxical corneal steepening. However, the effects of wound healing on these eyes were absent. The possibility of producing a corneal ectasia or an iatrogenic keratoconus exists, al¬ though there is no evidence of this from our preliminary topographic analysis. At the present time, we are per¬ forming some of our lower myopic ablations at diame¬ ters of 6.5 to 6.9 mm. In corrections over 9 or 10 D, the diameters are reduced to 6.0 mm to keep the ablation depth under 250 µ (Table 3). In corrections over 14 D, a multizone approach will be considered. Corneal topographic data show that there is a wider range of corneal powers within the central optical zone after PRK. Despite this, almost all of the patients con¬ tinue to have good visual acuity. Long-term evaluation of these patients will be useful to determine the stabil¬ ity of the corneal topography. Contrast sensitivity testing provides a different and sensitive means of evaluating the visual system, as contrast sensitivity can be markedly reduced despite near-normal visual acuity in several disorders.28,29 The subset of patients in this study had somewhat reduced contrast sensitivity before surgery and experienced no loss of contrast sensitivity after PRK. It is our clinical impression that the corneal haze seen in these deeper ablations was somewhat heavier than the haze seen in the lower myopic corrections (-1 to -6 D). However, there was no apparent relationship between the depth of cut and levels of haze. Individual variation in wound healing seems to be a more impor¬ tant variable. Other investigators have reported inthe

creased levels of corneal opacification with deeper lev¬ els of ablation.30·31 Some of these older studies were performed on earlier prototypes of various excimer la¬ sers in which "hot spots" and less than optimal beam homogeneity could be responsible for induced thermal effects and increased corneal haze. There may be sig¬ nificant qualitative differences in the homogeneity of the laser output in the three different machines cur¬ rently being studied in the United States. To date, there have been no studies comparing the quality of the laser output in terms of beam profile, beam uniformity, the presence of hot spots, and fluctuations in fluence on corneal tissue during a given treatment. The causes of the undercorrections and the regres¬ sions seen after excimer PRK and observed in several patients in this study are not well understood. All ab¬ lations stimulate keratocytes, which stimulate new collagen production. Liu et al31 postulated that deeper ablations may stimulate keratocytes to a greater ex¬ tent than superficial ablations and result in heavier deposition of collagen fibers that reverse the effect of surgery. Epithelial hyperplasia, as seen in patient 14, also cause regression of refractive effect. Some degree of epithelial hyperplasia is seen frequently after PRK and may be independent of fluence. It may cause more regression of effect in smaller-diameter ablation zones than in larger ones. The sporadic nature of the regres¬ sion or undercorrections observed may be the result of individual biologic variations in wound healing. The ef¬ fects of other patient variables such as age and sex await results from a larger series of patients. We did not encounter corneal epithelial complica¬ tions in this series other than the slower recontouring and smoothing of the epithelium. However, corneal surface problems do occur after PRK. In our most re¬ cent series of myopic PRK in myopia of -1 to -6 D (phase 3), we have noticed isolated instances of fila¬ mentary keratitis, focal noninfectious epithelial infil¬ trates, minor recurrent erosions, and persistent irreg¬ ular astigmatism (N.A.S., unpublished data, 1992). Careful and improved postoperative treatment will help keep these problems to a minimum. Another major cause of regression and haze may be the fluence (energy density of the laser pulse) of the laser output. Although the ablation and thermal dam¬ age zone is only 0.25 µ for a 193-nm ablation, it is still possible to stimulate keratocytes by acoustic shock waves much deeper into the stroma. For large-area ablations, the shock wave energy is approximately lin¬ ear with the fluence.32 It is possible that the use of higher fluences can cause larger and deeper stimulation of the keratocytes and induce more haze and regres¬ sion. There is some suggestive evidence to support this hypothesis when one looks at the fluence of the various existing excimer lasers. The Summit and VISX Twenty Twenty machines use 180 and 160 mJ/cm2 flu¬ ence, respectively, and in cases of high myopia, have had significant overcorrections followed by regression and increased haze. The Taunton/VISX Model 2000 and 2015 use a fluence of 120 mJ/cm2. The role of corticosteroids in preserving corneal clarity is speculative. Animal studies have shown that

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haze can be minimized83 by topical steroids. There is little clinical evidence in humans to support this. Gartry et al,4 in their large series, showed little difference in corneal haze in eyes that were treated with topical corticosteroids and in eyes that were untreated or dis¬ continued the corticosteroid drops early. In contrast to this, Seiler and Wollensak3 reported a higher incidence of significant corneal haze in patients who prematurely discontinued their corticosteroid treatment. The effect of steroids on modulating overcorrections and under¬ corrections is not clear and the question of steroid use will require controlled studies. We have recently begun to use the topical nonsteroidal prostaglandin inhibitor, 0.1% diclofenac sodium (Voltaren, CibaVision, Atlanta, Ga) after surgery, in the treatment of pain and inflammation after PRK. Cur¬ rently, one drop of diclofenac sodium is being used im¬ mediately after surgery and then four times per day for several days after surgery. It is our impression that there is a dramatic improvement in postoperative pain,

lid swelling, and conjunctival injection with no major detrimental effects on epithelial healing or haze (N. A.S., Charles Ostrow, MD, R.L.L., unpublished data, 1992). This preliminary study shows that excimer PRK may be useful for the treatment of higher levels of my¬ opia than previously believed possible. Considerable further investigation and longer-term studies are needed to confirm the safety and the efficacy of this new

technology.

This research was supported in part by grants from VISX Co, Sunnyvale, Calif; Health One Corp, Minneapolis, Minn; the Friends of Phillips Foundation, Minneap¬ olis; and the Humana Corp. All three centers received support for this study from VISX Co. Dr Sher and Ms Parker have received remuneration for travel expenses from Taunton/VISX Co. The other members of the Minnesota group include Emmett Carpel, MD, Charles Ostrov, MD, Donald Doughman, MD, from the Phillips Eye Institute, Minneapolis, and Leo McGuire, MD, from the Mayo Clinic, Rochester. We thank the following individuals for their contributions to this work. Frances A. L'Espérance, MD; Phillips Eye Institute: Irving Shapiro, MD, Kris Barnes, COT, Roger Wilson, Deborah Skelnick, Barbara Gilbert, and Trish Johnson, COMT; Su¬ san Sutton for the preparation of this article; VISX Co: S. Michael Sharp; Univer¬ sity of Louisville: Yvonne Cook, COT, Kelly D. O'Neill, MD, Dean R. Forgers, MD; Florida Eye Center: Robin Meyers, COA.

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