Changes in central corneal thickness and refractive error after thin-flap laser in situ keratomileusis in Chinese eyes

Laser in situ keratomileusis (LASIK) is a common procedure in refractive surgery [1]. It is known that LASIK can be associated with a rare but visually debilitating refractive instability called ectasia. To prevent corneal ectasia after LASIK, it is recommended that at least 250 μm of residual corneal stromal tissues should be left after ablation. Therefore, the thinner the corneal flap, the thicker the residual corneal stromal bed can be ablated. This is especially important for treating a high degree of myopia. Thin-flap LASIK can create thinner corneal flaps, thicker residual stroma beds, and its safety and efficacy are similar to those of normal LASIK [2].

Refractive stability is influenced by alterations in corneal curvature and corneal thickness, and refractive error usually takes up to 6 months to stabilize after LASIK. The present study aimed to determine the changes in central corneal thickness (CCT) and spherical equivalent (SE) values in Chinese patients following thin-flap LASIK surgery, to evaluate the associations between postoperative CCT changes with age, preoperative SE, and optical zone diameter, and to evaluate the associations between postoperative CCT changes with postoperative refractive error changes.

No free or incomplete flaps, or flaps with buttonholes occurred in this study. The CCT was found to be 531.6 ± 24.3 μm during the preoperative period. The CCT decreased significantly at 1 day after surgery (431.4 ± 38.4 μm, P < 0.05), and continued to decline at 1 week after surgery (422.6 ± 37.8 μm). At 1 month after surgery, CCT values significantly increased (427.2 ± 38.0 μm, P < 0.05), and continually increased at 3 and 6 months after surgery (434.4 ± 38.2 μm, P < 0.05, and 435.6 ± 38.0 μm, P < 0.05, respectively) (Fig. 1). Significant changes were detected in CCT values at each time point after thin-flap LASIK treatment (P < 0.05). The mean ΔCCT was 4.06 ± 9.99 μm.

The mean preoperative SE was −5.83 ± 2.30 D. At 1 day and 1 week postsurgery, it was 0.26 ± 0.58 D and 0.54 ± 0.52 D, respectively. There was a myopic shift over time. At 1, 3, and 6 months after treatment, the mean SE was 0.49 ± 0.53 D, 0.45 ± 0.49 D, and 0.37 ± 0.42 D, respectively (Fig. 2). We did not detect any significant change in SE at any time point after LASIK treatment (P > 0.05). SE values at 6 months after surgery were similar to the predicted SE values (predicted SE: 0.34 ± 0.30 D, P > 0.05). The mean ΔSE was 0.14 ± 0.57 D.

We did not detect any significant correlations between CCT changes and SE changes (different time point postoperative value minus 1 day postoperative value), when measured at different examination points (r = −0.087, P = 0.054). No regression occurred within 6 months. All patient UCVAs after surgery were better than 16/20.

Many types of methods can be used to measure corneal thicknesses, such as ultrasound pachymetry, anterior-segment optical coherence tomography (AS-OCT), Pentacam measurements, Orbscan measurements, and non-contact specular microscopy techniques. However, the values are not always consistent between the different instruments. In a long-term follow-up study, it was recommended to uniformly use the same kind of measuring instrument [3–5]. Non-contact specular microscopy is a commonly used method for corneal thickness measurement, with advantages including noninvasiveness, ease of operator use, and good examiner-independent reproducibility [6]. Non-contact specular microscopy can be an ideal technique for studying the corneal thickness changes after photorefractive keratectomy, because it is noninvasive, which is especially important during the early postsurgery stage. Changes of CCT values are very important for observation of corneal tissue healing responses after surgery.

In this study, we used non-contact specular microscopy to follow-up the CCT changes within 6 months post thin-flap LASIK treatment. We found that CCT values declined significantly at 1 day postsurgery, and continued to decline at 1 week. CCT values began to increase over time. Several processes occurred during the early postoperative period, including resorption of fluid introduced by intraoperative irrigation, biomechanical hydration shift, epithelial thickness modulation in response to laser ablation, and interface reflectivity changes. However, in many reported cases, the systematic changes are small after 1 week [7], and the posterior stroma is significantly thickened after 1 week postsurgery [8, 9]. Peng et al. [10] reported that just after LASIK surgery, keratocytes were activated by cytokines that induced collagen fiber synthesis. Keratocyte activation was strongest at 1 to 2 weeks, and persisted until 3 months after LASIK surgery [8, 9]. This could cause the increase in posterior stromal thickness, and may be why the CCT values continued to increase after 1 week postsurgery.

In this study, we show that from 1 week postoperatively, SE continually shifted to the myopic side over time. Corneal wound repair is believed to be a contributing factor in the gradual increase of corneal thickness and postoperatively in the development of refractive regression [11, 12]. Epithelial hyperplasia after photorefractive keratectomy (PRK) has been suggested to contribute to the loss of the postoperative refractive effect [13–16]. However, after LASIK surgery, epithelial changes were significantly reduced, and were not the main cause for refractive instability [17]. Avunduk et al. reported no significant changes in epithelial thicknesses at any time point after LASIK treatment [18]. MØller-Pedersen et al. demonstrated activated keratocyte-mediated rethickening of the photoablated stroma of myopic individuals [11]. They further demonstrated that corneal rethickening caused myopic regression mediated almost solely by stromal rethickening; only a minor contribution appeared to originate from restoration of the postoperative epithelial thickness [11]. In the present study, we found a significant increase in the CCT between 1 week and 6 months after surgery (422.6 μm versus 435.6 μm). The spheroequivalent refraction changed to the myopic side between these time points (0.54 D versus 0.37 D), but the difference did not reach statistical significance, and no significant correlation was detected between the SE value changes and the CCT value changes at different examination time points. Normally, it would be expected that a 10 μm to 15 μm rethickening of the posterior stroma would produce a 1 D myopic shift. However, in the present study, the much greater rethickening created only a small amount of refractive change. It is difficult to explain this refractive change with activated keratocyte-mediated rethickening of the photoablated posterior stroma. Avunduk et al. suggested that the most probable explanation is that the refractive change is induced by different refractive characteristics of activated keratocytes during LASIK surgery. Therefore, the anterior and posterior curvature and the refractive index may be shifting postsurgery, and these factors may also play a role [18]. However, we do not have any corneal curvature measurements to support this hypothesis.

Li et al. found that CCT increased within 12 months after LASIK surgery, and was correlated with age, preoperative SE, and corneal bed thickness (r = −0.554, r = 0.382, r = −0.352, respectively) [19]. Our present observations were similar, however, in our study the correlations were all weak (r < 0.2). The reason for this difference is unclear, and further study is needed to confirm this finding. In elderly patients, tissue regeneration ability is reduced therefore the possibility of refractive regression is lower. It is not recommended to overcorrect on LASIK in patients over 40 years old [14]. To prevent the occurrence of refractive regression after surgery in patients with high myopia, it is recommended to expand the optical zone diameter as large as possible, leaving sufficient corneal stromal tissues. We also retained a certain degree diopter that was corrected after surgery with eye glasses [15].

In conclusion, CCT decreased significantly at 1 day after surgery, and continued to decline at 1 week after surgery, then it increased over time. From 1 week postoperative, SE continually shifted to the myopic side, with increased time postsurgery.