In recent years, physiological ocular changes associated with pregnancy have been reported, including reduction of tear production and subsequent contact lens intolerance, diminished intraocular pressure, decreased corneal sensitivity, steepening of the corneal curvature, accommodation insufficiency, increased corneal thickness, and a possible overall change in refractive status of the eye.1–7 Despite the lack of consensus in the literature, most authors agree on the transient nature of these changes, reaching a significant level during the last trimester of pregnancy and resolving completely after delivery or the cessation of breast feeding.7 These changes have been suggested to represent part of the spectrum of physiological changes occurring during pregnancy due to hormonal alterations.
Multiple studies have reported a significant influence of these changes on the elasticity and biomechanics of the operated cornea and have even attributed some incidents of ectasia after laser in situ keratomileusis (LASIK) to pregnancy.8–10 Unfortunately, due to the small sample size of these studies, a definite correlation is yet to be established. Hence, we herein longitudinally investigate the postoperative stability of the cornea in a large sample of pregnant women who had previously undergone myopic LASIK treatment.
Patients and Methods
This prospective clinical study received approval by the ethics committee of our institution (Laservision.gr Clinical and Research Eye Institute) and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant prior to the intervention and all testing outlined herein.
Women who had previously undergone myopic LASIK in our center between 2001 and 2015 and reported at least one pregnancy at any time after the first year postoperatively were identified as possible participants in this study. Inclusion criteria were the following: no other ocular procedure prior to myopic LASIK or additional ocular surgery between LASIK and data interpretation; documented refractive stability for at least 1 year and had discontinued contact lens use for at least 1 week prior to the initial refractive procedure (LASIK); age between 20 and 48 years and an initial refractive spherical error from −1.00 and −14.00 diopters (D), astigmatism of 0.00 to −6.00 D, and central corneal thickness of at least 500 µm prior to the LASIK procedure; preoperative corrected distance visual acuity (CDVA) of better than 20/30; and enough available data during and after pregnancy. Exclusion criteria were not enough available data during and/or after pregnancy.
All LASIK procedures were performed by the same surgeon (AJK) in the same clinical and research center (LaserVision Clinical and Research Institute, Athens, Greece).
For LASIK cases performed from 2001 to 2006, the M2 microkeratome (Moria, Anthony, France) and the 200-Hz Allegretto excimer laser (WaveLight, Erlagen, Germany) were used. For procedures performed from 2006 to 2010, we used the IntraLase FS60 femtosecond laser (IntraLase, Advanced Medical Optics, Irvine, CA) and the 400-Hz Eye-Q excimer laser (WaveLight). After 2011, the Alcon/WaveLight refractive suite comprising the FS200 femtosecond and EX500 excimer lasers (Alcon Laboratories, Inc., Fort Worth, TX) was employed for all femtosecond laser–assisted LASIK procedures. Planned flap thickness was 110 µm and planned flap diameter was 8.5 mm for all cases. Topographic data were imported by the Vario topolyzer (WaveLight) and cornea pachymetric data were imported by the Oculyzer II (WaveLight), a Scheimpflug-based tomography device associated with the Refractive Suite,11 essentially based on the Pentacam HD (Oculus Optikgeräte, Wetzlar, Germany).
Parameters before pregnancy at 3, 6, and 12 months after LASIK were compared with the respective values during the third trimester of pregnancy and 12 months postpartum so that every participant in this study could serve as her own control, eliminating eventual confounding bias.
Parameters measured and evaluated included uncorrected distance visual acuity (UDVA), manifest refractive error in sphere, cylinder, and spherical equivalent, keratometry using Speedy-K (Righton, Tokyo, Japan), Placido-disc topography (Vario-WaveLight; Alcon Laboratories, Inc.), Scheimpflug-based tomography (Oculyzer II), and anterior segment optical coherence tomography (Avanti; Optovue, Fremont, CA) for corneal and epithelial thickness mapping at a 9-mm diameter.12 Dilated fundus examination including retinal periphery was performed in all cases. All data were recorded on digital media.
Descriptive and comparative statistics, analysis of variance, and linear regression were performed by Minitab software (version 16.2.3; MiniTab Ltd., Coventry, United Kingdom) for statistical analysis. Visual acuity is reported decimally and keratometry in diopters. Results are reported as mean ± standard deviation and range as minimum to maximum. In all parameters studied, data were normally distributed. All statistical tests were applied to the sample size of 128 eyes of the 64 patients. To eliminate any potential confounding bias, every participant in this study served as her own control, in the different timeframes described above. Employing a sample size of 128 eyes, the current study was found to be more than adequately powered, according to power analysis formulas for the desired margin of error in each parameter studied, and for a confidence level of 95% (P value of less than 5%, corresponding to Z = 1.96 in the power analysis formulas).
Table 1 presents the demographic and preoperative ophthalmologic characteristics.
Demographics and Ophthalmologic Characteristics
The postoperative courses of UDVA are presented in Figure 1A. The average spherical equivalent was −0.20 ± 0.43 D at 3 months after LASIK, −0.32 ± 0.34 D at 6 months after LASIK (P = .37), −0.63 ± 1.00 D at 12 months after LASIK (P = .25), −0.51 ± 0.82 D during the third trimester of pregnancy (P = .14), −0.39 ± 0.81 D at 1 year postpartum (P = .68) (Figure 1B). None of the differences between before pregnancy and during the third trimester or 1 year postpartum measurements was found to be statistically significant (all P > .05). The average sphere was 0.03 ± 0.49 D and cylinder was −0.47 ± 0.47 D at 3 months after LASIK, −0.16 ± 0.33 and −0.32 ± 0.30 D at 6 months after LASIK, −0.44 ± 0.83 and −0.36 ± 0.47 D at 12 months after LASIK, −0.21 ± 0.74 D (P = .23) and −0.58 ± 0.51 D (P = .48) during the third trimester, −0.37 ± 0.17 D (P = .90) and −0.5 ± 0.57 D (P = .95) at 1 year postpartum, respectively (Figures 1C–1D). Again, none of the comparisons revealed any statistically significant difference between the results (all P > .05). Average flattest and steepest keratometry values were 39.29 ± 2.51 and 40.57 ± 2.81 D at 3 months after LASIK, 39.29 ± 2.51 and 40.85 ± 1.90 D at 6 months after LASIK, 39.78 ± 2.77 and 40.76 ± 1.87 D at 12 months after LASIK, 39.24 ± 2.48 D (P = 0.95) during the third trimester, and 37.95 ± 1.59 D (P = .22) at 1 year postpartum (Figure 1E). None of the comparisons revealed any statistically significant difference between before pregnancy and during the third trimester or 1 year postpartum (all P > .05). Average central epithelial thickness was 61.40 ± 5.89 µm at 12 months after LASIK, 60.38 ± 7.04 µm (P = .22) during the third trimester, and 61.00 ± 5.65 µm (P = .81) at 1 year postpartum (Figure 1F). Again, no statistically significant difference was noted (all P > .05). Of note, one case revealed an asymptomatic peripheral retinal tear that was treated uneventfully with green laser retina photocoagulation.
Graph demonstrating (A) the course of uncorrected distance visual acuity (UDVA), (B) stability of refractive spherical equivalent, (C) stability of spherical refractive value, and (D) stability of cylinder refractive value perioperatively, during the third trimester of pregnancy (3tP), and at 1 year postpartum. (E) Corneal curvature variations were analyzed by means of the flat (K1) and steep (K2) keratometry parameters. (F) The black dots represent the mean value of the central epithelial thickness (µm) at 12 months after laser in situ keratomileusis, 3tP, and at 1 year postpartum. D = diopters
Estrogen receptors have been identified in the human cornea,13 and reduction in biomechanical stability of the cornea when exposed to high doses of estradiol has been shown in an ex vivo study in porcine cornea.14 Although these data may suggest that changes in estrogen levels such as those occurring during pregnancy could lead to ectasia after LASIK and refractive errors in pregnant females, Randleman et al.15 reported a statistically significantly higher risk for men to develop iatrogenic keratectasia.
Abnormal preoperative topographies, high corrections, age, and thin residual stroma have been described as risk factors for the induction of iatrogenic keratectasia after LASIK by the same group, with pregnancy not being included in those.15 There is consensus over the single most significant risk factor for the development of iatrogenic keratectasia being preoperatively undetected abnormal topographies such as preexisting subclinical keratoconus.16
Hafezi et al.8 reported a small case series of 5 pregnant patients after LASIK showing signs of iatrogenic keratectasia during pregnancy, although as they emphasize they “cannot rule out that some of the cases could have had a preexisting minimal corneal thickness at the lower end of the normal distribution (ie, 505 µm), a minor asymmetry and elevation at the posterior pole (ie, 12 µm at a reference sphere of 8 mm), or even keratoconus” (p. 242) underlying the importance of preoperative identification of corneas that are considered high risk for ectasia after LASIK, thus being at high risk for refractive instability during or after pregnancy.
Contrary to previous case series and reports describing refraction fluctuations or even corneal ectasia during or after pregnancy for operated corneas,8–10 hypothetically, due to lack of the biomechanical properties of the operated cornea to cope with the physiological hormonally induced changes during pregnancy, our prospective analysis of 128 eyes of 64 women with adequate data before pregnancy and postpartum failed to reveal any statistically significant change in any of the parameters studied either during or after pregnancy. UDVA, CDVA, spherical equivalent, sphere, cylinder, flattest keratometry values, and central epithelial thickness all showed no statistically significant change, suggesting a great stability of the operated cornea, as previously reported.11 These data also suggest that there was no significant change in the corneal epithelial thickness, which is routinely evaluated perioperatively for all refractive surgery patients in our center, as was the case in our previous extensive reports on epithelial remodeling in both dry eye and after LASIK as measured by anterior segment optical coherence tomography mapping.17–19
The composition of our sample group comprising eyes operated on for a wide range of myopic refractive errors should be taken into consideration when interpreting our results, in terms of significance. Although this provided us with the opportunity to test results within different correction levels, we acknowledge that in our study we did not include a large number of patients in each correction level. Stratum analysis in future studies with larger subgroups could possibly render statistically significant results within a specific myopic correction level.
Our results suggest that refractive and corneal stability after LASIK appears to be unaffected by pregnancy. Further research should be directed toward studying a population of peri-pregnancy women within a more limited correction zone for stratum-specific results to be rendered.
- López-Prats MJ, Hidalgo-Mora JJ, Sanz-Marco E, Pellicer A, Perales A, Díaz-Llopis M. [Influence of pregnancy on refractive parameters after LASIK surgery]. Arch Soc Esp Oftalmol. 2012;87(6):173–178.
- Pilas-Pomykalska M, Czajkowskii J, Oszukowski P. [Ocular changes during pregnancy]. Ginekol Pol. 2005;76(8):655–660.
- Schechter JE, Pidgeon M, Chang D, Fong YC, Trousdale MD, Chang N. Potential role of disrupted lacrimal acinar cells in dry eye during pregnancy. Adv Exp Med Biol. 2002;506(Pt A):153–157. doi:10.1007/978-1-4615-0717-8_20 [CrossRef]
- Akar Y, Yucel I, Akar ME, Zorlu G, Ari ES. Effect of pregnancy on intraobserver and intertechnique agreement in intraocular pressure measurements. Ophthalmologica. 2005;219(1):36–42. doi:10.1159/000081781 [CrossRef]
- Riss B, Riss P. Corneal sensitivity in pregnancy. Ophthalmologica. 1981;183(2):57–62. doi:10.1159/000309139 [CrossRef]
- Weinreb RN, Lu A, Beeson C. Maternal corneal thickness during pregnancy. Am J Ophthalmol. 1988;105(3):258–260. doi:10.1016/0002-9394(88)90006-2 [CrossRef]
- Park SB, Lindahl KJ, Temnycky GO, Aquavella JV. The effect of pregnancy on corneal curvature. CLAO J. 1992;18(4):256–259.
- Hafezi F, Koller T, Derhartunian V, Seiler T. Pregnancy may trigger late onset of keratectasia after LASIK. J Refract Surg. 2012;28(4):242–243. doi:10.3928/1081597X-20120401-07 [CrossRef]
- Padmanabhan P, Radhakrishnan A, Natarajan R. Pregnancy-triggered iatrogenic (post-laser in situ keratomileusis) corneal ectasia—a case report. Cornea. 2010;29(5):569–572. doi:10.1097/ICO.0b013e3181bd9f2d [CrossRef]
- Hafezi F, Iseli HP. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg. 2008;34(7):1219–1221. doi:10.1016/j.jcrs.2008.02.036 [CrossRef]
- Kanellopoulos AJ, Asimellis G. Long-term bladeless LASIK outcomes with the FS200 femtosecond and EX500 excimer laser workstation: the refractive suite. Clin Ophthalmol. 2013;7:261–269. doi:10.2147/OPTH.S40454 [CrossRef]
- Kanellopoulos AJ, Asimellis G. Comparison of high-resolution Scheimpflug and high-frequency ultrasound biomicroscopy to anterior-segment OCT corneal thickness measurements. Clin Ophthalmol. 2013;7:2239–2247.
- Suzuki T, Kinoshita Y, Tachibana M, et al. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res. 2001;22(1):28–33. doi:10.1076/ceyr.220.127.116.1180 [CrossRef]
- Spoerl E, Zubaty V, Terai N, Pillunat LE, Raiskup F. Influence of high-dose cortisol on the biomechanics of incubated porcine corneal strips. J Refract Surg. 2009;25(9):S794–S798. doi:10.3928/1081597X-20090813-06 [CrossRef]
- Randleman JB, Russell B, Ward MA, Thompson KP, Stulting RD. Risk factors and prognosis for corneal ectasia after LASIK. Ophthalmology. 2003;110(2):267–275. doi:10.1016/S0161-6420(02)01727-X [CrossRef]
- Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;115:37–50. doi:10.1016/j.ophtha.2007.03.073 [CrossRef]
- Kanellopoulos AJ, Asimellis G. In pursuit of objective dry eye screening clinical techniques. Eye Vis (Lond). 2016;3(1):1. doi:10.1186/s40662-015-0032-4 [CrossRef]
- Kanellopoulos AJ, Asimellis G. Epithelial remodeling following myopic LASIK. J Refract Surg. 2014;30(12):802–805.
- Kanellopoulos AJ, Chiridou M, Asimellis G. Optical coherence tomography-derived corneal thickness asymmetry indices: clinical reference study of normal eyes. J Cataract Refract Surg. 2014;40(10):1603–1609. doi:10.1016/j.jcrs.2014.01.041 [CrossRef]
Demographics and Ophthalmologic Characteristics
|Characteristic||Mean ± SD||Range|
|Age (y)||28||20 to 35|
|mpL||55||12 to 108|
|Spherical refraction (D)||−6.04 ± 3.01||−11.00 to −1.00|
|Cylindrical refraction (D)||−1.35 ± 1.00||−3.50 to 0.00|
|SE (D)||−6.72 ± 2.96||−11.12 to −2.12|
|UDVA||0.05 ± 0.11||0.01 to 0.50|
|K1 (D)||44.27 ± 1.33||41.90 to 47.10|
|K2 (D)||43.24 ± 1.81||43.90 to 51.70|
|CCT (µm)||551.73 ± 35.97||470 to 595|