For approximately two decades photorefractive keratectomy. Seven-Year Changes in Corneal Power and Aberrations after PRK or LASIK.

Transcription

1 Cornea Seven-Year Changes in Corneal Power and Aberrations after PRK or LASIK Anders Ivarsen and Jesper Hjortdal PURPOSE. To examine long-term changes in corneal power and aberrations in myopic patients randomized to photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). METHODS. Forty-five patients with myopia from 6 to 8 diopters (spherical equivalent refraction) were randomized to PRK (n ¼ 20) or LASIK (n ¼ 25). Patients were examined preoperatively and for up to 7 years after surgery. Measurements included refraction, topography (TMS-1), and ultrasound pachymetry. By 3 years, 16 PRK and 15 LASIK patients were examined and by 7 years, 9 PRK and 7 LASIK subjects were available. Only patients who had not been reoperated and attended the two late controls were included in data analyses. Optical analysis of topographic data was used to calculate corneal power and wavefront aberrations. RESULTS. PRK and LASIK caused a similar reduction in corneal power. During the first year after PRK, corneal power increased, but remained stable from 1 to 7 years. In contrast, corneal power continued to increase from 1 to 7 years after LASIK. Both PRK and LASIK caused an increase in coma-like and spherical aberrations that remained constant for 7 years. No significant changes in other higher-order aberrations were observed. CONCLUSIONS. The cornea may not be stable even 7 years after LASIK, as indicated by the continuing increase in corneal power. In contrast, PRK appears stable from 1 year post surgery. Coma-like and spherical aberrations are permanently increased after PRK and LASIK. (ClinicalTrials.gov number, NCT ) (Invest Ophthalmol Vis Sci. 2012;53: ) DOI: /iovs For approximately two decades photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) have been used to correct myopia. However, long-term studies are relatively few, and most studies are retrospective evaluations of the postoperative refractive outcome. 1 8 Several of these articles find a slight regression of myopia over time, even years after the initial surgical procedure. 1 4,6 This gradual change in refraction may be attributed to physiologic changes, including increasing axial length or lenticular changes, but may also indicate a lack of postoperative corneal stability. Biomechanical instability is of particular concern, with iatrogenic keratectasia From the Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark. Supported by The Danish Association for Prevention of Blindness and Bagenkop Nielsens Foundation. Submitted for publication May 16, 2012; revised July 30, 2012; accepted August 2, Disclosure: A. Ivarsen, None;J. Hjortdal, None Corresponding author: Anders Ivarsen, Department of Ophthalmology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; ai@dadlnet.dk. being acknowledged as a late risk of keratorefractive procedures Prospective long-term studies of corneal optical and topographic changes after keratorefractive surgery may help to increase the understanding of corneal biomechanical changes. In the present study, we reported long-term changes in corneal front-surface power and aberrations in patients randomized to PRK or LASIK for myopia between 6.00 and 8.00 diopters (D). METHODS Patients At the Department of Ophthalmology, Aarhus University Hospital, Denmark, we perform refractive surgery on several hundred eyes per year for myopia of more than 6 D. Between July and October 2000, patients were invited to participate in a prospective study of PRK and LASIK (Clinical trial identifier NCT ). One eye from each of 45 patients was included. Inclusion criteria included spherical equivalent refraction of 6.00 to 8.00 D, regular astigmatism of less than 1.50 D, stable refraction (<0.50 D change) for at least 2 years, and a monocular best spectacle corrected visual acuity (BSCVA) of 0.10 (logmar units) or better in both eyes. Exclusion criteria included previous ocular disease or eye surgery, young age (<19 years), susceptibility to keloid formation, and pregnancy or breast-feeding. The study protocol followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee of Aarhus, Denmark. Informed written consent was obtained from all participants after explanation of the nature and possible consequences of the study. Patients were randomized to PRK or LASIK using a random number system. Twenty-five subjects were randomized to LASIK, and 20 to PRK. Retreatments were not allowed within the first year after surgery. Surgery All surgical procedures were performed in topical anesthesia (3 drops of oxybuprocaine 0.8% with 5-minute intervals). To ease centration of the microkeratome suction ring, two drops of pilocarpine 2% were applied with 10-minute intervals. All operations were performed by the same surgeon (J.H.). In PRK, a circular corneal marker was used to define a central 8-mm zone centered over the pupil. A surgical sponge was used for very brief application (1 2 seconds) of 96% alcohol, followed by immediate wiping with a wet sponge. Subsequently, the central epithelium was removed with a blunt knife. Following the excimer laser treatment (see below), one drop of cyclopentholate 1%, one drop of diclofenac 0.1%, and chloramphenicol ointment were applied. The postoperative treatment consisted of chloramphenicol eye drops (0.5%) three times a day for 1 week and prednisolon eye drops (0.5%) three times a day, tapered over 3 months. In LASIK, a 9-mm corneal flap with a superior hinge was cut with a Schwind Supratome (Schwind, Kleinostheim, Germany) with a 130-lm cutting head. After laser treatment (see below) the flap was carefully repositioned. Cyclopentholate, diclofenac, and chloramphenicol eye Investigative Ophthalmology & Visual Science, September 2012, Vol. 53, No. 10 Copyright 2012 The Association for Research in Vision and Ophthalmology, Inc. 6011

2 6012 Ivarsen and Hjortdal IOVS, September 2012, Vol. 53, No. 10 TABLE 1. Patient Characteristics LASIK (n ¼ 25) PRK (n ¼ 20) Sex 12 female, 13 male 15 female, 5 male Age, y (range, 21 46) (range, 23 49) BSCVA (logmar) Spherical equivalent refraction, D Average cylinder, D Average keratometry, mm Central corneal thickness, lm Intraocular pressure, mm Hg Residual stromal thickness, lm (range, ) (range, ) Data are given as mean 6 SD. drops (one drop each) were administered and a bandage contact lens (Focus Night and Day; CIBA Vision, Duluth, GA) was inserted. The contact lens was removed on day 1, and chloramphenicol eye drops were prescribed twice a day for 1 week. In both PRK and LASIK the excimer laser photoablation was performed with a MEL-70 G-scan flying spot excimer laser (Meditec- Aesclepion, Jena, Germany). In all eyes, the optical zone was 6 mm in diameter, and identical photoablation nomograms were used for PRK and LASIK. Ultrasound pachymetry (BVI pocket pachymeter; BV International, Marcy L Etoile, France) was performed perioperatively before and after the excimer ablation. Astigmatisms of less than 0.75 D were included as part of the spherical correction, whereas astigmatisms from 1.00 to 1.50 D were treated with an attempted astigmatic correction of 1.00 D. There were no significant differences in the attempted cylinder correction between LASIKand PRK-treated patients. Examinations Patients were examined preoperatively and at 1, 3, 6, 12, 36, and 84 months after surgery. Measurements included manifest refraction, ultrasound pachymetry, and corneal topography (TMS-1; Tomey, Nagoya, Japan). Ray tracings from corneal topographic maps were performed as previously detailed. 14,15 In brief, the topography maps were converted to sagittal height data by integrating the first derivative of the dioptric data. The height data were subsequently transformed to a grid with 0.1- mm spacing and imported into an optical analysis program (Zemax-EE; Radiant ZEMAX LLC, Bellevue, WA). Ray tracings were performed for a 4-mm pupil, and the optimal focal length was determined by minimizing the root-mean-square (RMS) of the wavefront error relative to the image centroid. Reference to the centroid optimizes the wavefront by subtraction of piston and tilt. 15 Corneal radius of curvature and optical power were calculated from the optimal focal length by using a refractive index of Total corneal wavefront aberrations (RMS) were determined for pupil sizes of 2, 4, and 6 mm, and decomposed into optical components of defocus, regular astigmatism, coma, and spherical aberration. Aberrations that did not fit these categories were grouped as other higher-order aberrations. Standard Zernike notation was used. Analyses included only patients that attended the 3-year (36 months) or 7-year (84 months) controls and had not been reoperated. By 3 years, 16 PRK- and 15 LASIK-treated patients were available for follow-up, while only 9 PRK and 7 LASIK patients were able to attend the control after 7 years. The 3-year observations have previously been published in part. 16 Statistics Demographic parameters were compared with v 2 test. Temporal changes in spheroequivalent refraction, corneal front-surface power, total wavefront error, and individual aberrations were compared by using two-tailed, paired t-tests. Comparisons between PRK and LASIK were performed with two-tailed, unpaired t-tests. Where applicable, adjustment for multiple comparisons was performed by using the Bonferroni technique. Normal distribution was confirmed with the D Agostino-Pearson test. In all comparisons involving 7-year data, or in cases where the test for normal distribution failed, the Wilcoxon test for paired data or the Mann-Whitney test for independent samples was used. Correlations were performed with the Pearson correlation coefficient. Multiple linear regression analysis was performed to identify variables contributing to observed changes in corneal power. In all analyses a P value <0.05 was considered to be statistically significant. RESULTS Patients receiving PRK or LASIK were comparable with respect to age, spherical equivalent refraction, refractive astigmatism, best spectacle corrected visual acuity, keratometry, central corneal thickness, and intraocular pressure (Table 1). Furthermore, preoperative corneal front-surface power, total wavefront error, and individual aberrations were similar in PRK- and LASIK-treated patients. Significantly, more women than men received PRK (P < 0.05; v 2 test). Laser In Situ Keratomileusis During the first year after LASIK, there was a significant change in spheroequivalent refraction from D after 1 week to D after 1 year (P < 0.01, n ¼ 15; paired t- test). From 1 to 7 years, a further insignificant change in refraction of D was observed (Fig. 1). Corneal front-surface power gradually increased from D at 1 month to D at 12 months after LASIK (P < 0.01, n ¼ 15; paired t-test; Fig. 2). However, corneal power also increased significantly from 1 to 3 years (P < 0.05; n ¼ 7, Wilcoxon test) and from 3 to 7 years after surgery (P < 0.05; n ¼ 7; Wilcoxon test), an increase being observed for all individual patients attending the 7-year control. The observed changes in corneal power from 1 to 7 years were insignificantly correlated to changes in spherical equivalent refraction (Pearson s r ¼ 0.72; P ¼ 0.07). The changes in corneal power showed no correlation to the insignificant changes that could be observed in central corneal thickness (Pearson s r ¼ 0.17; P ¼ 0.71; Fig. 3). With multiple linear regression, the attempted refractive correction and the preoperative central corneal thickness, stromal bed thickness, axial length, corneal astigmatism, and total corneal wavefront error were not found to contribute significantly to the observed changes in corneal power from 1 to 7 years. For a 4-mm pupil, coma-like and spherical aberrations were significantly higher at all time points after LASIK than before surgery (P < 0.01; paired t-test and Wilcoxon test; Table 2). When increasing the pupil to 6 mm, the induced changes in

3 IOVS, September 2012, Vol. 53, No. 10 Changes in Power and Aberrations after PRK or LASIK 6013 FIGURE 1. Changes in spherical equivalent refraction for up to 7 years after PRK (n ¼ 9) or LASIK (n ¼ 7). No significant differences were observed between PRK and LASIK at individual time points. Data are given as mean 6 SEM. FIGURE 2. Seven-year changes in corneal front-surface power after PRK (n ¼ 9) or LASIK (n ¼ 7). No significant differences were observed between PRK and LASIK at individual time points. Data are given as mean 6 SEM. coma-like and spherical aberrations were further accentuated, and total wavefront error and defocus also increased over their preoperative values (Fig. 4). In contrast, no significant changes in other higher aberrations or astigmatism were found. For a 2- mm pupil, no changes in total wavefront error or individual aberrations were detected (Fig. 4). Photorefractive Keratectomy One week after PRK, spherical equivalent refraction averaged D. This was followed by a gradual change to D after 1 year (P < 0.05, n ¼ 16; paired t-test). From 1 to 7 years after surgery, a further insignificant refractive change of D was observed (Fig. 1). Corneal power increased from D at 1 month to D at 12 months after PRK (P <0.001 ; n ¼ 16; paired t-test; Fig. 2). No significant changes were observed from 1 to 7 years after surgery, and no significant correlation was found between changes in corneal power and spherical equivalent refraction (Pearson s r ¼ 0.00; P ¼ 0.99) or central corneal thickness (Pearsons s r ¼ 0.31; P ¼ 0.41; Fig. 3). Furthermore, there were no significant differences in postoperative power between PRK and LASIK at 3 or 7 years after surgery. For a 4-mm pupil, coma-like aberrations increased significantly over the preoperative value (P < 0.05, n ¼ 16; paired t- test) and remained unchanged from 1 month to 7 years after PRK (Table 2). Spherical aberration was also significantly increased 1 month after PRK (P < 0.001, n ¼ 16; paired t-test) but decreased somewhat during the first postoperative year (Table 2). At all time points from 3 months to 7 years after PRK, spherical aberration remained stable and significantly higher than before surgery (P < 0.01, n ¼ 16; paired t-test). For the 6- mm pupil, the observed changes in coma and spherical aberration were more pronounced than for a 4-mm pupil, and total wavefront error and defocus were also increased over the preoperative values (Fig. 4). For a 2-mm pupil no changes in individual aberrations could be detected, and at all pupil sizes, PRK caused no significant changes in other higher-order aberrations or astigmatism (Table 2, Fig. 4). For 4-mm and 6-mm pupils, the total wavefront error and the amount of spherical aberration were higher 1 month after PRK than after LASIK (P < 0.05, t-test). At all time points from 3 months to 7 years after surgery, no significant differences in corneal aberrations were detected between PRK and LASIK, although the total wavefront error and most individual aberrations appeared higher after LASIK (Table 2, Fig. 4). For a 2-mm pupil, no differences in individual aberrations were detected between PRK and LASIK at any time point, although PRK was found to have a higher total wavefront error 1 month after surgery (P < 0.01, t-test). FIGURE 3. Changes in central corneal thickness for up to 7 years after PRK (n ¼ 9) or LASIK (n ¼ 7). No significant differences were observed between PRK and LASIK at individual time points. Data are given as mean 6 SEM.

4 6014 Ivarsen and Hjortdal IOVS, September 2012, Vol. 53, No. 10 FIGURE 4. Corneal wavefront aberrations 7 years after PRK (n ¼ 9, black bars) or LASIK (n ¼ 7, open bars). Open circles indicate preoperative mean values. The asterisk (*) indicates significant difference from preoperative value (P < 0.05). No significant differences were observed between PRK and LASIK. Data are given as mean 6 SEM.

5 IOVS, September 2012, Vol. 53, No. 10 Changes in Power and Aberrations after PRK or LASIK 6015 TABLE 2. Corneal Wavefront Aberrations for a 4-mm Pupil after PRK or LASIK LASIK, 4-mm Pupil Pre (n ¼ 15) 1 Month (n ¼ 15) 1 Year (n ¼ 15) 3 Years (n ¼ 15) 7 Years (n ¼ 7) Total wavefront error, lm Astigmatism, lm Coma, lm * Spherical aberration, lm * Other higher order aberrations, lm PRK, 4-mm Pupil Pre (n ¼ 16) 1 Month (n ¼ 16) 1 Year (n ¼ 16) 3 Years (n ¼ 16) 7 Years (n ¼ 9) Total wavefront error, lm Astigmatism, lm Coma, lm * Spherical aberration, lm * * Other higher order aberrations, lm Data are given as mean 6 SD. * Significant difference (P < 0.05) from preoperative value. Significant difference (P < 0.05) from 1 month. DISCUSSION In the present study, front surface corneal power was demonstrated to increase for up to 7 years after LASIK for moderate myopia. Thus, 6 of 7 LASIK patients attending the late 7-year control showed increasing corneal power between 1 and 7 years as determined by optical analysis of topographic maps. Despite the small number of patients, changes were statistically significant and may suggest that the cornea may not be biomechanically stable even a very long time after LASIK for moderate myopia. To our knowledge, no other clinically controlled, prospective studies of long-term changes in corneal front-surface power have been published; however, in a retrospective study, Alió et al. 17 have reported an insignificant increase in corneal keratometry index between 3 months and 10 years after LASIK, whereas Miyai et al. 18 found no significant changes in anterior surface elevation during 4 years after PRK or LASIK. In a previous article, we reported the findings of 36 months follow-up on corneal power and aberrations from the same prospective study. We found that corneal power did not change significantly in neither LASIK nor PRK patients from 12 to 36 months. However, 10 of 15 LASIK patients in our previous study showed an increase in corneal power; eight of these had an increase of 0.5 D or more. In contrast, only two patients showed a decrease of more than 0.5 D, indicating a significant trend towards increasing corneal power (P ¼ 0.02; v 2 test for trend). Thus, the previous report may not contrast with the present observation of a significant increase in power from 1 to 3 years as well as from 3 to 7 years. The observed overall increase in corneal power after LASIK may be biased by positive selection of patients with continuing optical changes, since these patients will be more likely to attend the very late controls. Still, the results suggest that a relatively large proportion of LASIK-treated patients may have progressive subtle changes in corneal optical power as late as 3 to 7 years after surgery. In contrast to the observations after LASIK, no changes were observed between 1 and 7 years after myopic PRK. All patients in the present study had no more than 8 D of myopia and all patients but one, were well within the widely used empirical safety margin of 250-lm residual stroma. 10 Interestingly, the one patient with a residual stromal bed below 250 lm was the only LASIK patient who did not show an increase in corneal power. None of the patients in either group showed late topographic changes suggestive of iatrogenic keratectasia. Using multiple regression analysis, it was not possible to identify preoperative parameters with influence upon the observed increase in corneal power after LASIK, possibly owing to the small number of patients available. This makes it difficult to hypothesize on the cause of the detected changes. Although the increasing corneal power may suggest a potential lack of biomechanical stability in LASIK-treated corneas, central corneal thickness remained stable. Likewise, no indication of inferior steepening was identified since coma did not change. Another potential hypothesis for the increasing power could be discrete changes induced by continuing central corneal remodeling; however, it remains unclear why this should occur after LASIK but not after PRK. In accordance with previous studies, PRK and LASIK were found to increase spherical and coma-like aberrations, with a more pronounced increase for larger pupil sizes. 16,19,20 During the first year after PRK, the rather large increase in spherical aberration may be related to the changes in epithelial thickness that we have previously demonstrated to occur within the first year after surgery. 21 Otherwise, the observed changes in corneal aberrations remained unaltered even 7 years after surgery, strongly indicating that the induced changes are permanent. Although newer lasers and treatment algorithms may show higher refractive predictability and less induction of higher-order aberrations, the results suggest that surgically induced higher-order aberrations do not readily diminish over time. Unfortunately it is difficult to generalize the current data owing to the small number of patients. Still, the observed changes add to existing concerns regarding the long-term corneal stability after LASIK Larger, long-term studies focusing on changes in corneal optical parameters will be needed in order to elucidate the potential consequences of LASIK in the very long term. However, the concern about potential stability issues of traditional LASIK may diminish with newer treatment methods, such as ReLEx smile (Carl Zeiss Meditec, Jena, Germany), in which a refractive lenticule is cut with a femtosecond laser and extracted through a small peripheral incision, leaving most of the anterior corneal stroma intact. 22,23 References 1. Pietilä J, Mäkinen P, Pajari T, et al. Eight-year follow-up of photorefractive keratectomy for myopia. J Refract Surg. 2004; 20:

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