LASIK and Pregnancy
During pregnancy, many physiological changes occur. The ocular system is also affected by the fluctuating hormones. For instance, sex steroid and thyroid hormone receptors are found on the cornea although the effects of such hormones have not been fully elucidated. Nevertheless, previous studies have noted changes in corneal curvature correlating with the onset and progression of keratoconus and iatrogenic ectasia during pregnancy. There have been few case reports of corneal melting during pregnancy in women with a history of prior corneal surgeries. Considering the organic effects of pregnancy on the cornea, what are the visual changes in women who become pregnant status post laser-assisted in situ keratomileusis (LASIK)? The United States FDA lists pregnancy and breastfeeding as a contraindication to LASIK because of “temporary and unpredictable changes in your cornea" and because a "LASIK treatment may improperly change the shape of your eye.” Here we review some of the literature regarding these changes, as well as discuss observational and case studies involving LASIK and PRK in pregnant patients and explore the potential consequences of LASIK in the pregnant woman through a literature search.
Ocular Changes and Complications in Pregnancy
Corneal thickness has been shown to increase during pregnancy. Weinreb found that there was an increase in corneal thickness during pregnancy in 89 women varying from 1-16 microns compared to non gravid and postpartum controls. While this study found that gestational age did not affect changes in corneal thickness, others have noted ocular changes occur during the second and third trimesters of pregnancy.
Efe found that that central corneal thickness was significantly higher in the second and third trimester compared to the first trimester and 3 months postpartum. There was a 3.1% increase in central corneal thickness in the third trimester and this was associated with 9.5% decrease in intraocular pressure. 
In 54 pregnant women, Atas found that between the third trimester and 3 months postpartum there was a significant difference in central corneal thickness as well as in intraocular pressure, anterior chamber angle, anterior chamber volume, corneal volume, and keratometry measurements. 
Other studies have failed to find a significant increase in corneal thickness during pregnancy.  In 27 patients, Manchester found only a 0.001 difference in corneal thickness from pregnancy to postpartum. In a prospective study, Sen found no statistically significant difference in central cornea thickness in 32 pregnant women with matched controls. 
A proposed explanation for increased corneal thickness was increased body fluid retention during pregnancy. More recently, it is thought that the cornea may be directly affected by sex hormones. Estrogen receptors have been identified in the corneal stroma and endothelium.  Studies examining ocular changes with the menstrual cycle have also demonstrated an association with estrogen and corneal thickness. Fluctuations in estrogen levels in the blood with the menstrual cycle lead to changes in corneal thickness with increased thickness at ovulation and at the end of the menstrual cycle. 
Corneal curvature has been found to increase in pregnancy. 
In a prospective trial, Park found that there was increase in keratometry during each trimester in pregnancy and that this continued for those who breastfed. The corneal curvature returned to first trimester values after cessation of breastfeeding. 
In a separate prospective study, Goldrich studied 60 pregnant and non-pregnant women and found a steeper corneal curvature as well as a lower IOP in pregnant patients. 
These studies are contradictory however to a study done by Manchester who found a mean difference of only 0.01D in 25 patients.5
Changes in corneal curvature are thought to be secondary to increased levels of progesterone and estrogen that increase collagenolytic activity, which may lead to corneal steepening. 
A decrease in intraocular pressure during pregnancy has been described in several studies. There is no evidence that the decrease in IOP is due to changes on an anatomic level. Instead, it is thought that hormones such as progesterone, relaxin, and hcg lead to reduced episcleral venous pressure and increased aqueous outflow. 
There are conflicting opinions on whether or not refractive changes occur in pregnancy.
Despite changes in corneal curvature, Park found no change in refractive error. Similarly, Manges found no significant difference in spherical refractive correction or cylinder axis. There was less then .03D mean change in refractive error between pregnant and non-pregnant patients.
However, in a large survey by Pizzarello, 12/83 pregnant patients complained of visual changes. These women were found to have a myopic shift from pre pregnancy levels of 0.87D +/- 0.3 in the right and 0.98D +/- 0 .3 in left eye. The myopia returned to pre-pregnancy levels by 3 months postpartum.
Corneal sensitivity tends to decrease in pregnancy. Using a cochet bonnet aesthesiometer to stimulate the cornea, Millidot found that corneal touch threshold increased with advancing pregnancy and this was significant compared to controls in the third trimester. Within 6-8 weeks postpartum corneal sensitivity returned to normal. They also noted that greatest losses in corneal sensitivity occurred in women reporting swelling of ankles and fingers.
Using a draegers electromagnetic aesthesiometer, Riss Riss also found a decrease in corneal sensitivity.
Corneal sensitivity also decreased during the preovulatory estrogen peak during the menstrual cycle, suggesting an association with hormonal changes.
There appears to be an association with hormones and dry eye symptoms. Studies have shown that women have dry eye signs and report dry eye symptoms more frequently than men. Pregnant women have a decrease in tear production during the third trimester shown in 80% of women using the schirmer test.
The mechanism for dry eye associated with pregnancy is still unclear but possible explanations are alteration in tear production and inflammatory changes. A decrease in goblet cell population and secretion of mucin has been associated with increased levels of estrogen and progesterone. Changes in lacrimal gland function may also play a role in dry eye. Substantial changes in Na/K ATPase expression on lacrimal gland tissue in pregnant rabbits likely contributes to alterations in lacrimal gland secretion. The presence of 17-beta estradiol has been shown to increase the expression of inflammatory genes in corneal epithelial cells. This may contribute to symptoms of dry eyes as well.
Contact Lens Intolerance
It is common for women to develop contact lens intolerance during pregnancy. Park reported that 25% of pregnant patients developed contact lens intolerance, mostly in the second trimester. Similarly, 30% of soft or rigid contact wearers reported difficulty with their contacts in normal pregnancy, including discomfort, surface mucus deposition, increased awareness, and reduced wearing time. It is speculated that contact lens intolerance is secondary to corneal thickening, corneal steepening, and alteration in tear production.
Effects of Pregnancy on Refractive Surgery
The influence of pregnancy on the stability of the cornea after refractive surgery is an area of ongoing research.
PRK in Pregnant Patients
In pregnant patients, rearrangement of corneal fibrils after PRK may lead to higher sensitivity to hormonal changes in the cornea. A study by Shariff looked at refractive changes in nine women who became pregnant within 12 months following PRK. Of the nine patients, six had myopic regression, though the degree was not specified. Correlation was noted between regression of myopia and corneal haze, and 50% of eyes showed improved myopia and corneal haze one month after labor. On the other hand, Hefetz found that pregnancy did not influence the refractive results of PRK. They looked at eight women who became pregnant during follow up for PRK and found that six out of eight patients showed stable refraction. A case report by Starr showed overcorrection in a patient that became pregnant after myopic PRK, and then resolution after spontaneous abortion. These studies were limited in sample size and further study is needed in order to clarify PRK in pregnancy. Current recommendation is to wait at least 6 months following PRK before pregnancy.
LASIK in Pregnant Patients
There is limited literature on the effects of LASIK on the eye in pregnancy.
Kannellopoulos et al showed that pregnancy did not induce significant changes in refractive error, corneal stability, and total corneal and epithelial thickness in women after LASIK up to 1 year postop. An observational prospective study was done comparing refractive changes in nine pregnant women who previously underwent LASIK to nine pregnant women with refractive alterations who had no history of surgical correction. Alterations in spherical equivalent and cylinder values were statistically significant during the first half of pregnancy compared to pre-pregnancy in both the LASIK and non-LASIK group. In regards to spherical equivalent, it was found that those with smaller previous refractive defects exhibited a greater statistically significant change in spherical equivalent compared to those with larger previous refractive defects. The authors hypothesize that with less modification required by LASIK, larger amounts of stroma and estrogen receptors would be available to participate in edemitization, and a larger number of residual fibrils could restructure in a disorganized manner. They did not find any decrease in visual acuity, spherical refractive value, corneal curvature or axial length, but noted a tendency towards worsening visual acuity and refractive value throughout pregnancy that was more significant in patients with previous LASIK. Post-LASIK ectasia has been attributed in some cases to hormonal influences that occur during pregnancy. Late onset iatrogenic keratectasia was found to occur 4-9 years after LASIK in five pregnant patients. The authors suggest that pregnancy may increase the risk of keratectasia in predisposed individuals. In one case report, a woman developed iatrogenic keratectasia during her first pregnancy 36 months after LASIK. Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet energy stopped the progression and regression of keratometric steepness. However, during a second pregnancy keratectasia was exacerbated despite CXL. The authors postulate that estrogen reduces the biomechanical stability of the cornea, leading to iatrogenic keratectasia after LASIK.
A causal relationship between corneal ectasia status post LASIK in the pregnant woman cannot be definitively established due to confounding factors such as genetic predisposition for corneal ectasia or preexisting minimal corneal thickness, keratoconus, or asymmetry in the posterior pole. However, the confounding variables may easily have been worsened by the LASIK procedure and exacerbated by the subsequent hormonal surge found in pregnancy. Considering that estrogen receptors are in the cornea and the temporal relationship between pregnancy and ectasia the increased estrogen levels found in pregnancy likely contributes to LASIK-induced keratectasia. Some authors suggested to avoid PRK or LASIK during pregnancy and to postpone pregnancy until 6 months to one year after refractive surgery, or until a stable prescription is documented. Other resources recommend postponing LASIK for 3-6 months after pregnancy and cessation of breastfeeding. Thus, women of child-bearing age should be appropriately counseled on the potentially increased risk of corneal ectasia with pregnancy status post LASIK.
- American Academy of Ophthalmology. LASIK. American Academy of Ophthalmology. EyeSmart® Eye health. https://www.aao.org/eye-health/treatments/lasik-2. Accessed March 14, 2019.
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Goldich Y. Cooper M, Barkana Y, Tovbin J, Lee Ovadia K, Avni I, Zadok D. Ocular anterior segment changes in pregnancy. Journal of Cataract & Refractive Surgery. 40(11):1868-71, 2014 Nov.
- ↑ 2.0 2.1 2.2 Weinreb, R N, Lu, A, Beeson, C. Maternal corneal thickness during pregnancy. Am J Ophthalmol. 105(3):258-60, 1988 Mar 15.
- ↑ 3.0 3.1 Efe Y K, Ugurbas S C, Alpay A, Ugurbas S H. The course of corneal and intraocular pressure changes during pregnancy. Canadian Journal of Ophthalmology. 47 (2):150-4, 2012.
- ↑ 4.0 4.1 Ataş M, Duru N, Ulusoy D, Altınkaynak H, Z Duru, G Açmaz, F Ataş, G Zararsız. Evaluation of anterior segment parameters during and after pregnancy.Cont Lens Anterior Eye. 2014 Dec;37(6):447-50. doi: 10.1016/j.clae.2014.07.013.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Park S B, Lindahl K J, Temnycky G O, Aquavella J V. The effect of pregnancy on corneal curvature. CLAO Journal. 18(4):256-9, 1992 Oct.
- ↑ 6.0 6.1 6.2 Manchester PT Jr Hydration of the cornea. Transactions of the American Ophthalmological Society. 68:425-61, 1970.
- ↑ 7.0 7.1 Manges TD, Banaitis DA, Roth N, Yolton RL. Changes in optometric findings during pregnancy.American Journal of Optometry & Physiological Optics. 64(3):159-66, 1987 Mar.
- ↑ 8.0 8.1 Sen, Emine, Onaran, Yuksel, Nalcacioglu-Yuksekkaya, Pinar 1. Elgin, Ufuk. Ozturk, Faruk. Corneal biomechanical parameters during pregnancy.European Journal of Ophthalmology 2014;24(3):314-319
- ↑ Suzuki T1, Kinoshita Y, Tachibana M, Matsushima Y, Kobayashi Y, Adachi W, Sotozono C, Kinoshita S. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res. 2001 Jan;22(1):28-33.
- ↑ Kielly P M, Carney L G, Smith G. Menstrual cycle variations of corneal topography and thickness. Am J Optom Physiol Opt 198360822–829.829
- ↑ Giuffre G, Di Rosa L, Fiorino F. et al Variations in central corneal thickness during the menstrual cycle in women. Cornea 200726144–146.146
- ↑ Green K, Phillips CI, Cheeks L, Slagle T. Aqueous humor flow rate an, Keyd intraocular pressure during and after pregnancy. Ophthalmic Res. 1988;20(6):353-7.
- ↑ Weinreb r, Lu A, Key T. Maternal Ocular adaptation during Pregnancy. Obstetrical and Gynecological Survey. 1987; 42 (8) 471-483.
- ↑ Pizzarello LD. Refractive changes in pregnancy. Graefes Arch Clin Exp Ophthalmol. 2003;241:484–488
- ↑ Millodot M. The influence of pregnancy on the sensitivity of the cornea. British Journal of Ophthalmology. 61(10):646-9, 1977 Oct.
- ↑ Riss B, Riss P. Corneal sensitivity in pregnancy. Ophthalmologica. 183(2):57-62, 1981.
- ↑ Riss B, Binder S, Riss P, Kemeter P. Corneal sensitivity during the menstrual cycle. Br J Ophthalmol. 1982 Feb;66(2):123-6.
- ↑ Rapoport Y, Singer JM, Ling JD, Gregory A, Kohanim S. A Comprehensive Review of Sex Disparities in Symptoms, Pathophysiology, and Epidemiology of Dry Eye Syndrome. Semin Ophthalmol. 2016;31(4):325-36.
- ↑ 19.0 19.1 19.2 19.3 Imafidon CO, Imafidon JE. Contact lenses in pregnancy. Br J Obstet Gynecol. 1992;99:865–868
- ↑ Huang J, Lu M, Ding C.Na(+)/K(+)-ATPase expression changes in the rabbit lacrimal glands during pregnancy. Curr Eye Res. 2013 Jan;38(1):18-26
- ↑ Suzuki T1, Sullivan DA.Estrogen stimulation of proinflammatory cytokine and matrix metalloproteinase gene expression in human corneal epithelial cells. Cornea. 2005 Nov;24(8):1004-9.
- ↑ 22.0 22.1 22.2 Sharif K. Regression of myopia induced by pregnancy after photorefractive keratectomy. Journal of Refractive Surgery. 13(5 Suppl):S445-6, 1997 Aug
- ↑ 23.0 23.1 23.2 Hefetz L, Gershevich A, Haviv D, Krakowski D, Eshkoly M, Nemet P. Influence of pregnancy and labor on outcome of photorefractive keratectomy. Journal of Refractive Surgery. 12(4):511-2,1996 May-Jun.
- ↑ Starr MB. Pregnancy-associated overcorrection following myopic excimer laser photorefractive keratectomy. Archives of Ophthalmology. 116(11):1551, 1998 Nov
- ↑ Kanellopoulos AJ, Vingopoulos F. Does Pregnancy Affect Refractive and Corneal Stability or Corneal Epithelial Remodeling After Myopic LASIK?. J Refract Surg. 2020;36(2):118-122. doi:10.3928/1081597X-20200115-01
- ↑ López-Prats MJ1, 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 Jun:87(6):173-8
- ↑ 27.0 27.1 Hafezi F, Koller T, Derhartunian V, Seiler T. Pregnancy may trigger late onset of keratectasia after LASIK. J Refract Surg. 2012 Apr;28(4):242-3
- ↑ 28.0 28.1 Hafezi F, Iseli HP. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg. 2008 Jul;34(7):1219-21.
- ↑ Sharma S, Rekha W, Sharma T, Downey G.Refractive issues in pregnancy.Australian & New Zealand Journal of Obstetrics & Gynaecology June 2006;46(3):186-188
- ↑ Dinn R , Harris A, Marcus P. Ocular Changes in Pregnancy.Obstetrical & Gynecological Survey February 2003;58(2):137-144
- ↑ Bower K. Woreta F. Update on contraindications for laser-assisted in situ keratomileusis and photorefractive keratectomy. Current Opinion in Ophthalmology July 2014;25(4):251-257