Table 1: Patient demographics (n = 118) (58 LASIK and 60PRK).

Preoperative and Postoperative Changes

As the Kolmogorov-Smirnov test indicated that not all parameters followed a normal distribution, mean values with standard deviation, 95% confidence intervals and medians were reported.

In the PRK group, the mean increase in ET peak was 6.62 ± 1.31 μm (95% CI [3.99-9.25]). Statistically significant increases were observed in most HOAs (specifically Z31 and Z42, p<0.05 and p<0.01, respectively), while both Weber contrast (SC WEBER, p<0.05) and the logarithm of contrast sensitivity (CS LOGS, p<0.05) showed statistically significant decreases postoperatively. Significant changes were also noted in LOAs (Z00, Z11, Z02, all p<0.0001) and CDVA (p<0.001).

In the LASIK group, the mean increase in ET peak was 6.55 ± 1.26 μm (95% CI [3.97-9.14]), which was not statistically different from the PRK group. Contrast sensitivity (SC WEBER and CS LOGS) significantly decreased (both p<0.0001) and spherical aberration (Z40) significantly increased (p<0.0001). Similar to the PRK group, significant changes were observed in LOAs (Z00, Z11, Z02, all p<0.0001) and CDVA (p<0.002). However, unlike the PRK group, most other HOAs (Z22, Z31, Z3, Z42, Z44) did not show statistically significant changes.

Correlations Between Parameter Changes

Spearman correlation analysis in the PRK group revealed a statistically significant correlation between the change in ET peak and the change in both Weber contrast (ρ = -0.36, p<0.01) and the logarithm of contrast sensitivity (ρ = 0.42, p<0.01). Furthermore, changes in ET peak were significantly correlated with changes in LOAs (Z00: ρ = -0.43, p<0.01; Z02: ρ = -0.44, p<0.01; Z11: ρ = 0.41, p<0.01) and specific HOAs (Z31: ρ = 0.33, p<0.05; Z42: ρ = -0.37, p<0.01). Notably, no significant correlation was found between the change in ET peak and the change in CDVA.

In the LASIK group, Spearman correlation analysis showed no statistically significant correlation between the change in ET peak and the change in either Weber contrast or the logarithm of contrast sensitivity. Similarly, no significant correlations were found between the change in ET peak and changes in HOAs. However, significant correlations were observed between the change in ET peak and changes in LOAs (Z00: ρ = -0.30, p<0.05; Z02: ρ = -0.31, p<0.05; Z11: ρ = -0.31, p<0.05). Again, no significant correlation was found between the change in ET peak and the change in CDVA.

Discussion

In this study we investigated whether there is a correlation between the change of the ET with changes of the CS and the aberrations before and after PRK and LASIK surgery, on the corneal apex. We found that the ET increase after refractive surgery and the increment was found to have no statistical difference among PRK and LASIK. The corneal epithelium hyperplasia it is well established from previous studies. It is known that affected by the amount of myopia treated, treatment zone and preoperative epithelial thickness but not by stromal ingrowth which is more pronounced in PRK [1-4,7,8]. Moreover, no difference between groups suggests that the epithelial changes occur as function of changes in the anterior corneal curvature and not necessarily related to tissue removal. The corneal flattening in myopic eyes may resulted in postoperative epithelial thickening due to the lack of mechanical influences of the upper eyelid that polishes the corneal surface with blinking [9].

In PRK surgery changes in ET seemed to be correlated with changes of CS. This correlation is being studied for the first time. The ET increased after PRK in accordance to CS reduction and this was probably due to the fact that in PRK there is epithelial removal and regeneration. Corneal epithelial cells are the first cells involved in the corneal regeneration process after PRK [11]. During the reconstruction of the epithelium is likely to have a different quality of epithelial cells with differences in their shape, size and clarity. We may have alterations in corneal biomechanics as well as possible dry eye. Histological studies conducted in animals and in humans, have found that thicker epithelium after PRK caused by an elongation of the basal epithelial cells and an increased number of superficial cell layers [4]. Moreover, the new subepithelial interface after PRK also accumulates water that colocalizes with the hyaluronan [11]. The sharp demarcations of these zones create sharp shifts in refractive index in these areas, causing light scattering which may affect the CS.

Furthermore, changes in ET appeared to correlate with both low (Z00, Z02, Z11) and high-class corneal aberration such as coma (Z31) and high-class astigmatism (Z42).

Previous studies have shown that the PRK increased the ocular aberrations, reducing the optical performance of the eye undergoing treatment [12,13].  However, only recently, several concerns regarding the correction of refractive errors have been raised because of the inter-individual epithelial thickness profile variability and the associated potential refractive effect [14,15].   Ivarsen, et al., proposed that during the first year after PRK, the rather large increase in spherical aberration may be related to the changes in epithelial thickness that have been previously demonstrated to occur within the first year after surgery [2]. Seiler T, et al., 2000 also report an increase in HOAs caused by PRK surgery during epithelial remodeling [12].

In LASIK there was statistically increased in ET. This is in accordance to previous studies which indicated that LASIK induced increment in epithelial thickness of approximately 20% that persisted after surger [2,9]. According to Patel, et al., central corneal epithelium in LASIK increased 24% during the first year after surgery and remained stable during the next 7 years [4]. However, in Lasik there was no correlation among ET increasement and CS changes, contrary to PRK.  In LASIK there is a creation of the lateral cut of the cornea which does not seem to affect the changes of CS. while in PRK there was complex interaction of epithelial cells and activated keratocytes [9]. A totally regeneration-remodeling of the cornea, changes the corneal structure as the cells change in shape, composition and size. Case report has demonstrated epithelial hyperplasia with an increased number of cell layers after PRK, whereas the nature of the epithelial changes after LASIK are less clear. Moreover, Hyaluronan that is reactively formed in the corneal wound after PRK colocalized to the hydrated area of the corresponding location as revealed by quantitative microradiography. The findings suggest that hyaluronan causes local shifts in water content in the corneal wound and thereby also local shifts in transparency that may affect the CS [11].

Moreover, the interface between epithelium and corneal stroma is different among two techniques. Injury after PRK is in the surface stroma and exposed, whereas injury after LASIK is inner stromatic and not exposed. Both epithelium and stroma are injured after PRK, but only stroma is injured after LASIK. In other words, the loss of cell-cell contact between keratocytes contributes to myodifferentiation of stromal cells and intact epithelium is the key to the prevention of stromal cell myodifferentiation after photoablation [16].

In LASIK surgery, the change in ET was found to correlate with changes in LOAs (Ζ00, Ζ02, Ζ11), which did not affect the change in subjective vision. These means that the intended ablation affects the thickness of corneal epithelium postoperatively. Previously there where a number of studies show that HOAS increase after LASIK. Cheng, et al., refer that LASIK-related aberrations were affected by the width-diameter of the removed visual belt and have an effect on HOAs [17]. Larger optical zone reduced overall HOAs as well as spherical aberrations, after LASIK. The effects were more significant in high myopia than in low [16]. Also, the high refractive corrections both myopic and hyperopic can result in very high levels of HOAs after LASIK surgery [18]. However, this is the first study which show that there was no correlation among HOAS increment and postoperative epithelial thickness. LASIK does not significantly affect high-order aberrations, which may be due to the individualized design (wavefront-guided / topography-guided LASIK).

More specifically, modern LASIK techniques based on wavefront or topography try to correct existing high-order aberrations or not worsen them. It may also be due to the smooth restoration of the anterior corneal profile: Modern excimer lasers have extremely precise eye trackers and smoothing software that allow for very uniform tissue removal. This limits the induction of HOAs, especially when the flap is created with a femtosecond laser. Finally, another factor is the preservation of normal corneal geometry: The LASIK method, unlike PRK, largely preserves the natural state of the surface layer of the cornea (epithelium and Bowman’s membrane), which can lead to a more stable visual result [19].

As it was mentioned above, postoperative corneal ET did not affect postoperative subjective vison in both techniques. This is in accordance to previous studies which mentioned that postoperative refractive changes correlate with changes in stroma (PRK) and corneal thickness (PRK and LASIK) but not with changes in ET [2].

A limitation of this study was applying statistical analysis to both eyes in some cases. The inclusion of bilateral cases was performed in order to increase the power of the study and reduce the number of subjects to be recruited. The optimal way to deal with this issue is to use only one eye from each patient or to use advanced statistical analysis. However, this was not always the case in all publications. However, in previous studies published in the literature in PRK or LASIK patients, it was found that correlations were low in eyes that had undergone refractive surgery and that results were similar when one or both eyes of the patients were used [5].

Conclusion       

In conclusion, the change of the epithelium thickness in both techniques had presented no statistically significant difference. However, the change in ET seemed to correlate with CS solely in PRK group. The difference between the two types of surgery can be related to the change in the shape of the cornea, the conversion of biodynamics, the healing of the corneal flap and the reconstructed of corneal epithelium and the layer. Moreover, the change of ET affected the aberrations in both techniques, but not in the same manner.

Value Statement

What Was Known

• Refractive surgery changes the shape of the cornea
• Changing the shape of the cornea affects vision, contrast sensitivity, epithelium and Zernike
• Changing all this affect the final vision

What This Paper Adds

• There postoperative epithelial of the cornea association with the contrast sensitivity
• There is no association of the corneal epithelium with the visual outcome
• The two techniques behave differently in terms of how they affect the thickness of the epithelium and the contrast sensitivity

Conflict of Interest

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding Details

No author has a financial or proprietary interest in any material or method mentioned.

References

1. Salomão MQ, Ambrósio R, Wilson SE, Belin MW. Corneal epithelial remodeling after LASIK and PRK: A review. J Refract Surg. 2017;33(4):282-9.
2. Ivarsen A, Laurberg T, Hjortdal J. Central corneal epithelial thickness changes after LASIK for myopia: A histological study. Acta Ophthalmol. 2009;87(1):68-73.
3. Chen S, Feng Y, Stojanovic A, Jankov MR, Wang Q. Changes in corneal epithelial thickness profile after transepithelial photorefractive keratectomy for myopia. J Refract Surg. 2015;31(2):104-10.
4. Patel S, Marshall J, Fitzke FW. Refractive effects of corneal epithelial remodeling following photorefractive keratectomy. J Refract Surg. 2007;23(6):565-71.
5. Gialelis TK, Tsiklis NS, Georgiou E, Vogiatzakis E, Gkika MG, Georgopoulos G. Contrast sensitivity and corneal aberrations analysis in relation with epithelial thickness changes at the corneal apex after refractive surgery. J Surg. 2021;13(6).
6. Bach M. The Freiburg visual acuity test—automatic measurement of visual acuity. Optom Vis Sci. 2006;83(8):545-50.
7. Kanellopoulos AJ, Asimellis G. Epithelial remodeling after partial topography-guided normalization and high-fluence short-duration crosslinking (Athens protocol): Results up to 1 year. Clin Ophthalmol. 2012;6:97-101.
8. Lohmann CP, Guell JL, Marshall J, Mrochen M. Corneal epithelial thickness changes after myopic photorefractive keratectomy. J Cataract Refract Surg. 1999;25(8):1057-60.
9. Erie JC. Corneal wound healing after photorefractive keratectomy: A 3-year confocal microscopy study. Trans Am Ophthalmol Soc. 2003;101:293-333.
10. Gan L, Fagerholm P, Palmblad J. Human corneal wound healing after excimer laser keratectomy: A 3-year in-vivo confocal microscopy study. Invest Ophthalmol Vis Sci. 2001;41(2):410-8.
11. Weber B, Fagerholm P, Johansson. Colocalization of hyaluron and water in rabbit corneas after photorefractive keratectomy by specific staining for hyaluronan and by quantitative microradiography. Cornea. 1997;16:560-3.
12. Seiler T, Kaemmerer M, Mierdel P, Krinke HE. Ocular optical aberrations after photorefractive keratectomy for myopia and myopic astigmatism. Arch Ophthalmol. 2000;118(1):17-21.
13. Verdon W, Bullimore M, Maloney RK. Near vision contrast sensitivity after photorefractive keratectomy. Arch Ophthalmol. 1996;114(12):1465-72.
14. Salah-Mabed I, Saad A, Gatinel D. Topography of the corneal epithelium and Bowman layer in low to moderately myopic eyes. J Cataract Refract Surg. 2016;42:1190-7.
15. Arba-Mosquera S, Awwad ST. Theoretical analyses of the refractive implications of transepithelial PRK ablations. Br J Ophthalmol. 2013;97:905-11.
16. Nakamura K. Interaction between injured corneal epithelial cells and stromal cells. Cornea. 2003;22(7 Suppl):S35-47.
17. Cheng ZY, Chu RY, Zhou XT. Influence of diameter of optical zone ablation on LASIK-induced higher order optical aberrations in myopia. Zhonghua Yan Ke Za Zhi. 2006;42(9):772-6.
18. Pesudovs K. Wavefront aberration outcomes of LASIK for high myopia and high hyperopia. J Refract Surg. 2005;21(5):S508-12.
19. Amin MH, Kamal MA, Sherif AM, Abdel Hafez MA, Abdallah KK. Changes of higher order aberrations after using wavefront guided LASIK and topography guided LASIK for correction of refractive errors: A comparative study. J Clin Exp Ophthalmol. 2022;13(6).