Corneal Topography Six Years After ... - Vision Engineering

Corneal Topography Six Years After Photorefractive Keratectomy for Myopia and Myopic Astigmatism Sebastiano Serrao, MD, PhD; Giuseppe Lombardo, Eng, PhD; Marco Lombardo, MD, PhD; Marino Palombi, MD; Cynthia J. Roberts, PhD ABSTRACT PURPOSE: To analyze the 6-year response of corneal topography to photorefractive keratectomy (PRK) for myopia and myopic astigmatism. METHODS: Twenty patients (40 eyes) who had PRK using the Technolas Keracor 217C excimer laser platform were followed up to 6 years after surgery. The eyes were subdivided into three groups according to the preoperative spherical equivalent refraction and astigmatism component. Corneal topographic maps were obtained with a Placido disk topographer (Keratron Scout). The pre- and postoperative topographical data were imported into custom software, which computed the average composite corneal map and average difference map for each study group to quantify the anterior corneal changes following laser ablation. The software defined three concentric zones of the surface topography, allowing characterization of the regional corneal response following surgery. RESULTS: At 6 years, no changes in the surface topographic configuration of the central cornea were assessed following spherical myopic ablations in comparison with 1 year postoperatively. A slight peripheral flattening of approximately 0.60 diopters (D) (P.001) was measured following the higher myopic ablations at 6 years compared with 1 year postoperatively. Minimal changes, of approximately 0.30 D (P.001), in the anterior central cornea were observed following astigmatic correction during follow-up. CONCLUSIONS: Photorefractive keratectomy for the correction of myopia provides stable corneal topography, with no clinically significant changes in the curvature profile at 6 years after surgery. [J Refract Surg. 2009;25:451-458.] DOI:10.9999/1081597X-20090422-08

T

he study of corneal biomechanic response to an ablative procedure introduced new questions about the accuracy and predictability of the Munnerlyn shape–subtraction model of photorefractive keratectomy (PRK). This model assumes a biologically and biomechanically inert cornea, which does not consider laser–tissue interactions or the biophysical responses of the tissue.1 On the other hand, biomechanical changes can manifest clinically as either immediate modification of corneal topography or as shape instability over time with long-term variations of the curvature gradients.2 Also, after surface ablation procedures, epithelial and stromal healing can affect the predictability of refractive and visual outcomes. During recent years, novel methods and techniques have been developed to improve the accuracy of surface ablation surgery. Among these are PRK with smoothing,3,4 wavefront-guided PRK,5 laser epithelial keratomileusis,6 and epiLASIK.7 Moreover, numerous authors are reporting long-term refractive outcomes of surface ablation procedures.8,9 On the other hand, these studies are based on analysis of old generation laser treatments with narrow optical zones, with ablation profiles and parameters that are no longer used. The consequence is that these data are not useful for comparison with current laser surgery outcomes. Generally, authors have reported, as a common occurrence after surface ablation, a mean early postoperative refractive regression of approximately 0.50 diopters (D) during the first year after treatment

From Serraolaser, Rome, Italy (Serrao); CNR-INFM LiCryL Laboratory, Physics Department, University of Calabria, Rende (CS), Italy (G. Lombardo, M. Lombardo); Vision Engineering, Rome and Reggio Calabria, Italy (G. Lombardo, M. Lombardo); Department of Ophthalmology, St John Hospital, Rome, Italy (Palombi); and the Departments of Ophthalmology and Biomedical Engineering, The Ohio State University, Columbus, Ohio (Roberts). The authors have no financial or proprietary interest in the materials presented herein. Correspondence: Sebastiano Serrao, MD, PhD, Via Orazio 31 - 00193 Rome, Italy. Tel/Fax: 39 380 333 11 00; E-mail: [email protected] Received: January 12, 2008; Accepted: October 29, 2008 Posted online: January 15, 2009

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Corneal Topography 6 Years After PRK/Serrao et al

and a slow myopic regression for up to 8 years of follow-up.8-10 In addition to the roles of the anterior and posterior corneal curvatures,11,12 the refraction of the eye’s optical system may depend on more variables, such as age-related changes of the lens and vitreous.13,14 Several studies investigated the changes in corneal topography with age in the normal population.15,16 They agreed that the anterior cornea tends to become steeper with age, with changes of approximately 0.25 D in the mean simulated keratometry value between 20 and 40 years. Because laser ablation reshapes the corneal surface and induces a mechanical response to the change in its structure,1,2,17 in addition to the expected longevity of patients undergoing refractive procedures, it is important to investigate whether progressive remodeling of the cornea occurs in the years following refractive surgery. In a previous study,18 we reported data of the topographic response of the cornea to PRK with smoothing for myopia at 4 years postoperatively in a group of 15 patients (none of whom is included in the present study) for a total of 30 eyes and demonstrated how the anterior cornea undergoes minimal remodeling up to 4 years after surface ablation, with curvature changes similar to a normal population. In the present study, we analyzed the 6-year postoperative response of corneal topography to PRK performed to correct simple myopia and myopic astigmatism. PATIENTS AND METHODS Between January and April 2001, 40 eyes of 20 patients (9 men, 11 women) underwent refractive surgery. Mean patient age was 33.635.24 years (range: 27 to 41 years). This was a prospective study of a larger group of 60 eyes that underwent PRK in that period. Ten patients (20 eyes) were unavailable for one of the protocol examinations; for this reason, they were excluded from the study. Inclusion criteria were patient age of at least 21 years with at least 1 year of refractive stability and a preoperative spherical equivalent (SE) refraction from 2.00 to 9.00 D. Exclusion criteria were the presence of previous ocular surgery or any ocular pathology. Patients were asked to discontinue the use of contact lenses for at least 4 weeks prior to surgery. Patients were divided into three groups according to the preoperative SE refraction and astigmatism component: high myopia (15 eyes), low myopia (15 eyes), and myopic astigmatism (10 eyes). The SE refraction was 2.510.69 D (range: 2.00 to 4.00 D) in the low myopia group and 6.001.59 D (range: 4.50 to 9.00 D) in the high myopia group; the cylinder component was 1.00 D in both groups. One patient was 452

anisomyopic; thus the 2 eyes were split into the two spherical study groups. The mean preoperative SE refraction of the astigmatic group was 4.772.59 D, with the cylinder component from 2.00 to 5.50 D. All astigmatic eyes were with-the-rule astigmatism. All patients signed an informed consent explaining the nature of the study, which followed the tenets of the Declaration of Helsinki. SURGICAL PROCEDURE Photorefractive keratectomy was performed with a Technolas Keracor 217C excimer laser (Bausch & Lomb Chiron Technolas, Dornach, Germany) with a 6.0-mm optical zone and a transition zone up to 9.0 mm. The smoothing technique was performed after the refractive ablation.4 All surgeries were performed by one surgeon (S.S.). The corneal epithelium was removed using the Amoils brush (Innovative Excimer Solutions Inc, Toronto, Canada). The refractive ablation was a standard nomogram with the factory settings; an active eye tracker device was used. This was followed by phototherapeutic keratectomy (using a viscous masking 0.25% sodium hyaluronate solution [smoothing technique]) at the end of the procedure, as described previously.3 The smoothing technique proved to be more effective in inducing less higher order aberrations than standard PRK.7 The astigmatism group was treated with a cross-cylinder technique with a 6.0-mm ablation zone diameter and a transition zone up to 9.0 mm in diameter. This technique consists of ablating half the power of the cylinder along the steepest meridian and half along the flattest meridian before the residual SE is treated. TOPOGRAPHIC ANALYSIS All patients underwent complete ocular evaluation including corneal topography (Keratron Scout; Optikon 2000, Rome, Italy), both preoperatively as well as at each postoperative examination interval, ie, at 1, 2, 4, and 6 years after surgery. A series of three maps was required for each temporal interval to assess the reliability of corneal topography acquisition. One single map was then used for analysis. All pre- and postoperative topographies were taken by a single observer (M.L.). The Keratron software allows the exportation of topographic measurements computed from 28 rings and 256 meridians for a maximum area of analysis of 5.0-mm radius for each patient’s eye. The pre- and postoperative topographic data were exported to custom software written in MATLAB (software version 7.0; MathWorks Inc, Natick, Mass). The mathematical algorithm computed the average tangential curvature map and the journalofrefractivesurgery.com


average elevation map for each study group, preoperatively as well as postoperatively, with respect to the reference axis.19 For the elevation maps, the pre- and postoperative surfaces were fitted tangentially to the apex. Any tilts between the corneal elevations were avoided by aligning the data with one another. Interpolation to the same spaced referenced corneal grid was necessary for this purpose, as discussed previously.20 The average differences in the maps obtained at 1, 2, 4, and 6 years postoperatively compared to preoperatively were also calculated. A “fixed” color scale, visually similar to that used in current videokeratography instruments, was developed for rapid and easy interpretation. The corneal reference frame was divided into three concentric regions for analysis: the central zone with a radius of 2.00 mm from the corneal apex, the paracentral zone with a radius of 2.00 to 2.50 mm, and the peripheral zone with a radius of 2.50 to 4.00 mm from the apex (Fig 1). This was done to separately analyze the central and peripheral zones of the front surface of the cornea. The custom software also performed subsequent data analysis: the mean curvature valuesstandard deviation of each analyzed zone were computed for all study groups. The average difference between the preoperative and two successive postoperative curvature values, or between early postoperative and late postoperative values, were also calculated for each corneal zone. The reproducibility and accuracy of the topographic map reconstructions performed by the software were tested using an artificial spherical cornea provided by the manufacturer and calculated from five independent measurements. Reproducibility was on average 0.11 D for a sphere of 43.40 D, and it was found to be similar to that achieved by the videokeratoscope itself, ie, 0.12 D.20 STATISTICS Multivariate analysis of variance for repeated measures was used to compare 1- and 6-year postoperative corneal topographic data between low and high myopia groups. The differences between the postoperative topographic data of the astigmatic group were compared using the analysis of variance procedure. A P value .05 was considered statistically significant for all tests performed. We calculated the statistical power of the test to be 0.65 for detecting topographic differences of 0.25 D (with a standard deviation of 0.30 D). Safety and efficacy indices were calculated as the ratios between the 6-year postoperative best spectaclecorrected visual acuity (BSCVA) and the preoperative BSCVA and the 6-year postoperative uncorrected visual acuity and the preoperative BSCVA, respectively. Journal of Refractive Surgery Volume 25 May 2009

Figure 1. Cornea reference frame (r4, 5.00 mm in radius): the inner region with a radius of 2.00 mm (sc1), the paracentral region with a radius of 2.00 to 2.50 mm (sc2), and the outer region with a radius of 2.50 to 4.00 mm (sc3). The inner region allowed measurement of the topographic changes inside the optical zone.

RESULTS REFRACTIVE ANALYSIS The 6-year follow-up data confirmed that all procedures were safe and effective with a safety index of 1.04, 1.10, and 1.47 in the low myopia, high myopia, and astigmatism groups, respectively. In the low myopia group, we reported an efficacy index of 1.02 versus 1.01 in the high myopia group and 1.03 in the astigmatism group. Table 1 summarizes the SE refraction for each study group during follow-up. No eye included in the study was submitted to laser retreatment. TOPOGRAPHICAL ANALYSIS Table 2 summarizes the average topographic values for each corneal zone in the study groups both pre- and postoperatively. The mean differences between the postoperative and preoperative corneal topographies are summarized in Table 3. SPHERICAL CORRECTION No significant changes in the surface topography of the central cornea were assessed following myopic ablations during follow-up (Figs 2 and 3). At 6 years postoperatively, no statistically significant curvature changes were measured for the paracentral corneal region following lower myopic ablations, whereas a minor flattening of 0.30 D (P.001) was measured for the deeper ablations in comparison with 1 year postoperatively. Accordingly, the topographic response of 453


TABLE 1

Pre- and Postoperative Mean Spherical Equivalent Refraction of the 40 Eyes That Underwent PRK Spherical Equivalent Refraction (MeanStandard Deviation) (D) Examination Interval

Low Myopia Group (n=15)

High Myopia Group (n=15)

Astigmatism Group (n=10)

2.510.69

6.001.59

4.772.59

1 year

0.040.28

0.120.30

0.440.72

2 years

0.040.21

0.070.26

0.480.65

Preoperative Postoperative

4 years

0.140.27

0.240.51

0.540.49

6 years

0.170.13*

0.380.51*

0.600.37*

Paired t test: *P.05 (between 1 and 6 years postoperatively).

TABLE 2

Anterior Tangential Average Curvature of the Three Analyzed Corneal Zones in Each Study Group Pre- and Postoperatively Anterior Tangential Average Curvature (D) Corneal Zone: Radius (R, mm)




43.641.30

45.081.13

45.001.77

Central Zone: 2.00 mm Preoperative Postoperative 1 year

41.961.16

40.981.77

41.291.13

2 years

41.941.26

40.941.83

41.221.00

4 years

41.971.08

41.121.85

41.281.15

6 years

41.961.19

41.131.99

41.571.31*

43.071.32

44.450.88

44.301.91

Paracentral Zone: 2.00R2.50 mm Preoperative Postoperative 1 year

42.451.27

43.351.01

41.351.64

2 years

42.341.52

43.021.16

41.481.80

4 years

42.501.12

43.131.01

41.361.82

6 years

42.381.11†

43.061.02*,†

41.672.27*

40.361.20

41.831.71

42.533.00

1 year

41.990.62

44.791.42

42.013.21

2 years

41.911.09

44.331.27

43.114.41

4 years

42.120.90

44.191.23

41.803.49

6 years

41.990.90†

44.201.10*,†

42.123.64

Peripheral Zone: 2.50R4.00 mm Preoperative Postoperative

Analysis of variance: *P.001 (between 1 and 6 years postoperatively), and †P.001 (between the low and high myopia groups).

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TABLE 3

Anterior Tangential Average Regional Late Postoperative Minus Early Postoperative Differences for the Three Study Groups Anterior Tangential Average Regional Differences (D) Corneal Zone: Radius (R, mm)




Central Zone: 2.00 mm 4 years postop 1 year postop

0.0180.52

0.1330.22

0.0150.19

6 years postop 1 year postop

0.00040.39

0.1420.30

0.2790.36

6 years postop 4 years postop

0.01880.23

0.0090.17

0.2950.32

0.0510.71

0.2220.30

0.0170.38

Paracentral Zone: 2.00R2.50 mm 4 years postop 1 year postop 6 years postop 1 year postop

0.0740.49

0.2980.25

0.3210.78


0.1250.30

0.0760.38

0.3030.75

0.1260.47

0.5940.40

0.2140.28

6 years postop 1 year postop

0.0090.51

0.5880.44

0.1140.57


0.1360.47

0.0060.32

0.3290.43

Peripheral Zone: 2.50R4.00 mm 4 years postop 1 year postop

the paracentral corneal zone was significantly related to the amount of refractive correction (P.001). The depth of ablation also significantly influenced the remodeling of the peripheral corneal region among groups (P.001). A statistically significant flattening of approximately 0.60 D (P.001) was measured at 4 years postoperatively compared with 1 year postoperatively, which remained stable at the end of follow-up in the high myopia group. On the other hand, no curvature changes were noted in the peripheral corneal region following shallower ablations postoperatively. ASTIGMATIC CORRECTION The anterior cornea was shown to remain remarkably stable between 1 and 4 years postoperatively. Changes in the curvature values were assessed between 4 and 6 years postoperatively, where the anterior cornea was shown to steepen in all regions of analysis by approximately 0.30 D (Fig 4). Results are summarized in Tables 2 and 3. DISCUSSION The anterior surface of the cornea is subject to continuous remodeling, even in normal eyes15,16; it is therefore a main point of interest to investigate whether progressive remodeling of the cornea in the years following refractive surgery is due to the effects of surgery itself, and principally, if the surgery can affect the mechanical stability of the tissue. The magnitude of the biomechanical response has been related to Journal of Refractive Surgery Volume 25 May 2009

the amount of the attempted treatment and irregularity of the ablated surface.7,19,21 The latter factor has been pointed out as the principal cause for abnormal epithelial and stromal remodeling, with higher variability in the outcome of surgery as a direct consequence.22 Photorefractive keratectomy with smoothing3 was shown to minimize stromal irregularities after ablation with faster re-epithelialization and improved visual performance, allowing surgeons to predict the refractive outcome and its stability more accurately.4,23,24 In a previous work,18 analyzing the corneal topography response to PRK in a group of 30 myopic eyes during 4-year follow-up, we demonstrated a slight but statistically significant central steepening of the cornea, of approximately 0.25 D, and a significantly different response of the peripheral cornea in relation to the amount of refractive correction. The aim of the present study was to extend this knowledge to the long-term response of the cornea after laser ablation and reconfirm our previous analysis and hypothesis. To do this, we investigated a larger and different population of myopic eyes and also introduced in the analysis eyes that underwent astigmatic correction. In this context, the topography responses of low and high myopia corrections have been directly compared and analyzed to detect postoperative curvature changes 0.25 D over a period of 6 years, which have been reported as a physiologic occurrence in a normal population of the same age. We included in this study only eyes of a group of patients (40 eyes) for 455


Figure 2. Average composite corneal maps obtained from the right and left eyes of the low myopia group during follow-up (color scale bar: diopters). The software allowed the representation of the corneal topographies separately for the right and left eyes of each study group. Following the lower ablations, minor changes, although significant, were noticed between 1 and 6 years postoperatively.

which all topographic data for each examination protocol interval were available. On the other hand, at 6 years, refractive results from the remaining eyes in that group (20 eyes) were similar to those reported here, as well as patient satisfaction. In the current series, at 4 years postoperatively, the surface topography responses to spherical ablations 456

Figure 3. Average composite tangential curvature difference maps from the right and left eyes of the high myopia group (color scale bar: diopters). Difference maps from A) 1 year minus preoperative and B) 6 years minus preoperative. The optical zone diameter appeared to be unmodified between 1 and 6 years postoperatively. Difference maps from C) 6 years minus 1 year postoperative and D) 6 years minus 4 years postoperative. In the years following the deeper ablations, the central corneal region showed steepening, whereas the corneal periphery flattened.

were similar to those of a previous study,18 with no clinically significant curvature changes in the central cornea and a different response of the peripheral cornea in relation to the amount of refractive correction. Differences in the regional response of the cornea in relation to the ablation profile and laser parameters may depend on the different postoperative strength distribution in the specialized architecture of stromal collagen lamellae induced by laser surgery.25-28 The cutting of collagen fibrils could enhance inhomogeneity in the journalofrefractivesurgery.com


biomechanics of the corneal stroma. It is also possible that wound healing may play a definitive role,29 resulting in an additional variable that may influence the long-term shape of the surgical cornea. With regards to the results of laser ablation for the correction of myopic astigmatism, slight although statistically significant changes in the anterior corneal topography, of approximately 0.30 D, have been observed between 4 and 6 years postoperatively. A higher variability in the measurement of curvature values was noticed in the peripheral corneal region both pre- and postoperatively. This may be related to the toricity of the cornea and the hyperopic treatment of cross-cylinder technique in the periphery. Moreover, the higher asymmetrical ablation of collagen lamellae in an astigmatic correction30 may induce a differential relaxation in stromal lamellar tension, resulting in the diffuse anterior corneal steepening measured at the end of follow-up; however, without resulting in ectasia.31 The limitation of our work was the lack of the regional corneal thickness measurements as performed by scanning-slit topography. Also, the calculated statistical power of our analysis was lower than 0.8 and most of the topographic changes following surgery fall within the measurement error of the topographical device. Hence, a larger population of eyes could enhance the power significance of our analysis and hypothesis. Photorefractive keratectomy for the correction of low to moderate myopia up to 9.00 D was shown to be a safe and effective refractive procedure during a 6-year postoperative period. The slight myopic shift, which may not be clinically significant, was shown to be similar to the distribution of the physiologic agerelated shift observed in the normal, adult population of the same myopic degree and age.32 Also, the corneal tissue was shown to maintain a stable central curvature profile, with no significant changes in the long-term postoperative period. Detailed mapping of the long-term corneal topography response after surgery may provide additional valuable information on the mechanical properties of the cornea and be highly beneficial for developing predictive models to optimize corneal surgery. AUTHOR CONTRIBUTIONS Study concept and design (S.S., M.L.); data collection (M.L., M.P.); interpretation and analysis of data (S.S., G.L., M.L., M.P., C.J.R.); drafting of the manuscript (S.S., G.L., M.L., M.P.); critical revision of the manuscript (S.S., G.L., M.L., M.P., C.J.R.); statistical expertise (G.L.); supervision (S.S.)

Journal of Refractive Surgery Volume 25 May 2009

Figure 4. A) Preoperative, B) 1-year, and C) 6-year average composite maps of the astigmatic group are represented (color scale bar: diopters). Average tangential difference maps from D) 6 years minus preoperative and E) 6 years minus 1 year postoperative. After the astigmatic correction, the anterior cornea steepened in all regions of analysis by approximately 0.30 D.

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