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Direct measurement of anterior corneal curvature changes attributable to epithelial removal in keratoconus

Ziaei, Mohammed MB ChB (Hons), FRCOphth*; Meyer, Jay MD, MPH; Gokul, Akilesh BOptom (Hons), PhD; Vellara, Hans BOptom (Hons); McGhee, Charles N.J. DSc, FRCOphth

Author Information
Journal of Cataract & Refractive Surgery: January 2018 - Volume 44 - Issue 1 - p 71-77
doi: 10.1016/j.jcrs.2017.10.044
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Abstract

The corneal epithelium is a moldable, nonkeratinized stratified layer with a reported thickness of between 48 μm and 53 μm.1,2 It has an asymmetric thickness profile, being slightly thicker inferiorly and nasally than superiorly and temporally. There is a larger inferosuperior difference than a nasotemporal difference in epithelial thickness.3 The corneal epithelial thickness profile has a demonstrable effect on the total corneal power. It governs the shape of the air–tear film4 and affects the tomographic analysis of this interface. The epithelium is thought to account for an average of 1.03 diopters (D) of central corneal power (2.0 mm diameter zone)5 and contributes to the power and axis of the corneal astigmatism.6

In keratoconic eyes, the corneal epithelium shows a localized thinning over the cone that is surrounded by an annulus of epithelial thickening.7 It has been postulated that epithelial thickness mapping can be a sensitive means for the diagnosis of keratoconus.8–12

The contribution of the epithelium to corneal refractive power in keratoconus is of special importance because in recent years, corneal surface reshaping procedures have been developed to improve the corneal shape by combining transepithelial photorefractive keratectomy (PRK) and corneal crosslinking (CXL).13–15

The present study sought to determine the differences between the tomographic features of the corneal epithelium and Bowman layer in eyes with keratoconus. To our knowledge, there has been only 1 previous in vivo study (using specular corneal topography) characterizing the role of the corneal epithelium on the anterior corneal shape and curvature in eyes with keratoconus.16 In the present study, a dual rotating Scheimpflug combined with Placido tomography analyzer (Galilei G2, version 6.1.3, Ziemer Ophthalmic Systems AG) was used to assess the tomographic changes induced by the removal of the corneal epithelial layer in keratoconic patients having CXL.

Patients and methods

This prospective study enrolled patients with keratoconus having CXL from August 2016 to April 2017 who were attending the University of Auckland Cornea and External Eye Disease Service, Greenlane Hospital, Auckland District Health Board, Auckland, New Zealand. The study was approved by the local Health and Disability Ethics Committee, a branch of the Ministry of Health in New Zealand. Written informed consent was obtained from all patients after they voiced understanding of the purpose and the procedures of the study in accordance with the tenets of the Declaration of Helsinki.

The inclusion criterion was progressive keratoconus diagnosed based on clinical and associated tomographic findings. Progressive keratoconus was defined as 1 or more of the following changes over 12 months: an increase of 1.00 diopter (D) or more in the steepest keratometry (K) measurement, an increase of 1.00 D or more in the manifest cylinder, or an increase of 0.50 D or more in manifest refraction spherical equivalent. The keratoconus stage was assessed using the Krumeich et al. classification.17 Exclusion criteria were contraindications to CXL, including corneal scarring or edema visible on slitlamp examination a history of contact lens wear, ocular surgery, or trauma. One eye of each patient was included in the study.

Patient Assessment

All patients received a complete ocular assessment before surgery including slitlamp biomicroscopy and ocular fundus examinations. Corneal tomography was obtained using the Galilei Dual Scheimpflug Analyzer. The Galilei dual Scheimpflug analyzer combines dual rotating Scheimpflug cameras and a Placido disk. The flash illumination is an output from a 475 nm wavelength blue light–emitting diode (ultraviolet free); it measures more than 122 000 datapoints per scan. Height data acquired from the Scheimpflug edges and slope data from the Placido images are transformed into height data. The combined height data are merged and used to create a surface fit of the anterior cornea through a proprietary algorithm.18,19

Measurements and Surgical Technique

Ten minutes before the planned CXL procedure, a preoperative tomography scan was performed in the operative eye using the dual Scheimpflug analyzer, which was located in the same room as the crosslinking unit. Three consecutive scans were performed by the same experienced examiner. All measurements were performed without pupil dilation and under identical lighting conditions between 1:00 pm and 5:00 pm to limit the influence of overnight corneal swelling.20 With their chins on the chinrest, patients were asked to fixate on the target light; they were also asked to blink completely immediately before each measurement to allow for adequate tear-film coverage over the corneal surface. The examiner checked each scan and its quality before recording it; only scans of acceptable quality were included.

Immediately after data acquisition, 2 drops of proxymetacaine hydrochloride 0.5% were administered and a speculum was placed between the eyelids. Under an operating microscope, an ethanol 20.0% solution was applied over 20 seconds in the central 8.0 mm corneal zone using a cornea well. The epithelium was then removed using a blunt spatula. The corneal surface was rinsed with a balanced salt solution and inspected to ensure that all epithelial remnants had been removed. The lid speculum was removed, and a further 3 consecutive tomography scans were acquired. No eyedrops were administered after epithelial debridement; however, the patient was asked to blink to optimize the tear film. The examiner checked each scan and its quality before recording it; only scans of acceptable quality were included. The patient returned to the surgical bed, and the CXL procedure resumed with the application of riboflavin solution composed of dextran-free riboflavin 0.1% with hydroxylpropyl methylcellulose (Vibex Rapid, Avedro, Inc.), with 10 minutes of corneal soaking. Corneal crosslinking was performed using an ultraviolet-A (UVA) source system (KXL, Avedro, Inc.) with 4 minutes of continuous UVA exposure at 30 mW/cm2 and an energy dose of 5.2 J/cm2. Treated eyes were dressed with a soft contact lens bandage for 3 days and medicated with ciprofloxacin and fluorometholone eyedrops 4 times a day for 3 days.

Measurements Variables

The average value of 3 consecutive high-quality scans were recorded for the following anterior and posterior corneal surface variables:

  • Corneal dioptric power in the flattest and steepest meridian of the 3.0 mm central zone.
  • Maximum K power on the anterior axial or anterior instantaneous curvature map.
  • Corneal astigmatism in the 3.0 mm central zone (toricity).
  • Asphericity in the 8.0 mm diameter central zone aligned to the first Purkinje q = Symbol.
  • Symbol
    Symbol
  • Pachymetry at the central (0.0 to 4.0 mm), midperipheral (4.0 to 7.0 mm), peripheral (7.0 to 10.0 mm), and thinnest points of the cornea.
  • Total cornea power calculated using ray tracing from a zone of 1.0 to 4.0 mm.
  • Spherical aberration in the 6.0 mm diameter central zone aligned to the pupil.

Statistical Analysis

Statistical analysis was performed using SPSS for Windows software (version 19.0, IBM Corp.). When data had a normal distribution, as shown by the 1-sample Kolmogorov-Smirnov test, parametric analysis (2-sided t test) was used. A P value less than 0.05 was considered statistically significant.

Results

Demographics

The study comprised 30 eyes of 30 patients. Twenty-eight eyes (93%) were graded as stage II and 2 eyes (7%) were graded as stage III on the Amsler-Krumeich classification system. The mean quality of the scan before epithelial debridement versus after debridement was 88.38% and 86.86%, respectively (P = .13). There were no intraoperative or postoperative complications, and the epithelialization rate was within normal limits in all patients after CXL. Table 1 shows the patients’ demographics.

Table 1
Table 1:
Demographics of patients included in the study.

Keratometry

Table 2 shows the anterior K values of the patients. There was significant steepening of the anterior axial corneal curvature after epithelial debridement in the central and midperipheral corneal zones but not in the peripheral zone (P < .01, P < .02, and P < .72, respectively) (Figures 1 and 2).

Figure 1
Figure 1:
Representative tomography maps of a patient before epithelial debridement.
Figure 2
Figure 2:
Representative tomography maps of a patient after epithelial debridement.
Table 2
Table 2:
Mean anterior axial keratometric variables and asphericity values before and after epithelial removal.

Table 3 shows the posterior K values of the patients. There was no significant difference between the posterior axial corneal curvature before and after epithelial debridement in the central, midperipheral, or peripheral corneal zones (P = .07, P = .11, and P = .21, respectively).

Table 3
Table 3:
Mean posterior axial keratometric variables and asphericity values before and after epithelial removal.

Asphericity

The mean anterior corneal asphericity as expressed by the Q value was significantly reduced after epithelial removal (ie, the anterior cornea became more prolate) (P < .01), whereas no significant difference was detected in mean posterior corneal asphericity after epithelial debridement (P = .23).

Total Corneal Power and Spherical Aberration

Table 4 shows the difference in total corneal power and total corneal wavefront spherical aberration values before and after epithelial removal at a 6.0 mm zone. There was no significant difference between the total corneal wavefront spherical aberration before and after epithelial debridement (P = .35); however, the total corneal power increased significantly (P < .01).

Table 4
Table 4:
Difference in total corneal wavefront spherical aberration and total corneal power values before and after epithelial removal.

Pachymetry

Table 5 shows the central, midperipheral, peripheral, and thinnest-point corneal thickness values in the patients. The central and midperipheral pachymetric measurements were significantly reduced after epithelial debridement (both P < .01); however, no statistically significant difference in the peripheral and thinnest-point pachymetric measurements was seen (P = 0.83 and P = .15, respectively).

Table 5
Table 5:
Mean central, midperipheral, peripheral, and thinnest-point corneal thickness measurements before and after epithelial removal.

Discussion

In this study, we analyzed the effect of corneal epithelial debridement in keratoconic eyes having CXL using combined Scheimpflug and Placido tomography to assess keratometry, asphericity, total corneal power, spherical aberration, and pachymetry. The mean change in the central corneal thickness (CCT) after epithelial debridement was 21 μm ± 14 (SD). The central epithelial thickness in eyes with keratoconus has previously been reported to be 43 ± 6 μm as measured by time-domain optical coherence tomography (OCT) (OCT 2000 system, Humphrey-Zeiss),21 45 ± 5 μm as measured by very high-frequency ultrasound (Artemis, Arcscan, Inc.),7 and 49 ± 5 μm as measured by Fourier-domain OCT (RTVue, version 5.5, Optovue, Inc.).12 Although a previous study reported that CCT measurements were comparable between Fourier-domain OCT and Scheimpflug tomography,22 this difference in epithelial thickness measurements might be explained by the inherent differences in the above measurement modalities. The devices use different reference points for central measurements, and values may be averaged or computed from across variable ranges, which may lead to differences in corneal thickness measurements after epithelial debridement.23 The corneal epithelial thickness at the thinnest point of the cornea has previously been reported to be 7.5 μm thinner than at the corneal vertex in keratoconic eyes.7 This, coupled with the variability of the corneal thickness measurements after exposure to an alcohol solution, might explain the lack of a statistically significant difference in the thinnest-point pachymetric measurement after epithelial debridement in this study.

In our study, the results show that the intact keratoconic cornea had a significantly lower keratometric axial power than that of Bowman layer in the central zone and a significantly higher keratometric axial power in the midperipheral zone. Several studies have evaluated the effect of the corneal epithelium on corneal topography in healthy cadaver corneas. Zipper et al.24 evaluated corneal topographic data before and after epithelial debridement in 16 fresh human cadaver eyes using a corneal topography system (CTS, Par Vision Systems Corp.) mounted on an operating microscope. They reported a difference in the apical radius of curvature of approximately 0.5 D within the central 7.0 mm zone. Simon et al.5 measured corneal topography in 10 fresh human cadaver eyes with the Topographic Modeling System (Computed Anatomy) before and after removal of the epithelium and reported the optical power of the epithelium to be 1.03 D within the central 2.0 mm zone and 0.85 D within a 3.6 mm zone.5 Salah-Mabed et al.25 studied the corneal topographic changes after epithelial debridement in myopic patients having PRK using a Placido topographer (OPD-Scan II, Nidek Co., Ltd.). The group reported that the epithelium acts like a convex–concave meniscus, reducing the paraxial keratometric corneal power in myopic eyes by 0.56 D in the central 1.0 to 5.0 mm cornea zone. In contrast, Gatinel et al.26 reported that the cornea was more prolate and the central cornea curvature was flatter after epithelial removal in 44 myopic patients having PRK. They found a reduction in corneal power of 0.96 D in the central 3.0 mm zone as measured by Placido topography (Orbscan II, Bausch & Lomb, Inc.). The differences between the preceding studies might be explained by the difference in measurement protocols, devices, and patient populations.

The data in this study suggest that the corneal epithelium remodels in corneal ectasia to flatten the central cornea and steepen the midperipheral cornea by acting as a convex–concave meniscus in the center and a concave–convex meniscus in the midperiphery. This is in keeping with previous work that showed that the corneal epithelium has the potential to modify the anterior corneal curvature and maintain the optical quality of the eye through a process of remodeling to compensate for stromal surface abnormalities seen in eyes with flap irregularities or irregular stromal ablation after refractive surgery.8,27 In brief, the epithelium tends to smooth stromal abnormalities by being thicker over the corneal “valleys” and thinner over the “hills.”28–30 This remodeling capacity has been hypothesized to be of greater importance in eyes with keratoconus because it masks some of the initial stromal corneal anomalies seen in early or subclinical ectasia.16 The degree of epithelial change appears to correlate with keratoconus severity and might be useful in monitoring disease progression.7 However, the behavior of the corneal epithelium in keratoconus appears to be complex. In 1 study,28 this reactive epithelial hyperplasia in biomechanically unstable corneas neutralized after biomechanical stabilization through CXL. The epithelium became nonreactive and conformed to a more normal thickness profile despite the highly irregular underlying stromal contour. Therefore, it has been suggested that the epithelial thickness profile might be a useful adjunct to topographic variables in detecting ongoing corneal changes after CXL.28,31 In addition, the initial regrowth of an epithelial layer of uniform thickness could paradoxically result in apparent steepening of the cornea immediately after CXL.

The results in this study are in alignment with those in a preliminary study by Touboul et al.,16 in which irregularity indices, asphericity, and K readings increased after epithelial removal in 8 eyes with keratoconus, as measured by Placido topography (Eyesys Vision, Inc.). In their study, the mean effective refractive power decreased by approximately 4 times the normal value and the average simulated K decreased by 2 times as a result of modification by the epithelium. The authors concluded that the stromal bulge caused by the ectatic process was significantly reduced by epithelial remodeling.

The results in this study indicate that the anterior corneal surface assumes a more prolate shape after epithelial removal at the level of Bowman layer in keratoconus. This is in alignment with previous findings that indicate a reduction in the mean anterior corneal asphericity of −0.07,25 −0.18,32 and −0.2126 after epithelial removal in healthy eyes and of −0.7616 in keratoconic eyes.

This study has several limitations. There is a lack of quantification of the magnitude of the eyelid opening, duration of corneal exposure after epithelial debridement, and head tilt during the scanning process. These factors might have resulted in variability in the quality of the tear-film profile between patients and led to some underlying stromal edema or dehydration, which therefore induced artifacts in the topographic maps. The contact between tear film and Bowman layer also has been postulated to increase corneal prolateness and steepening, which could result in overestimation of keratometry and asphericity values.25 Furthermore, exposure of alcohol to the epithelial surface can lead to dehydration of the underlying corneal stroma and changes in tomographic variables. Also, changes in the peripheral cornea could not be completely characterized because the diameter of epithelial debridement within the peripheral zone was limited.

In conclusion, this study found that the corneal epithelium plays an important masking role in the anterior corneal topographic variables in keratoconic eyes. The cellular basis for the above changes has not been elucidated and requires additional research. This masking effect of the corneal epithelium is important, especially in an era in which excimer laser systems are being customized to treat the shape of Bowman layer (subtracting the epithelial profile from the corneal surface topography) to improve the results of therapeutic, transepithelial, and topography-guided surface ablations.31 This precise programming of the epithelial thickness into the ablation nomogram of transepithelial topography-guided treatments might reduce the error resulting from the masking properties of the corneal epithelium and treat the true tomographic and wavefront variables of Bowman layer. A previous study by Vinciguerra et al.33 found that custom Bowman layer–based ablations were successful in treating highly aberrated, nonectatic corneas using intraoperative, topography-derived measurements after epithelial debridement.

Further studies are required to evaluate the effect of epithelial regrowth on surface irregularity after CXL by repeating tomographic measurements after epithelial debridement in keratoconic patients having PRK after CXL. Such studies would differentiate between stromal changes induced by CXL and the epithelial remodeling effect on corneal tomographic changes seen after CXL. Future research evaluating the role of the epithelium on true retinal image quality by measuring this Bowman layer’s impact on higher-order aberrations as well as corneal tomographic variables may allow for the formulation of a laser-adjustment nomogram that takes into account keratoconus severity and preoperative tomographic variables, which may improve the safety and efficacy of PRK and CXL. Until further research occurs, caution should be used when performing simultaneous dual treatments, such as combined CXL and topography-guided photoablation, when refractive accuracy is targeted in patients because the preoperative topographic measurements may not be truly representative of the shape of Bowman layer.

What Was Known

  • The corneal epithelium in keratoconic eyes shows a localized thinning over the cone surrounded by an annulus of epithelial thickening.

What This Paper Adds

  • Results indicate that the corneal epithelium plays an important masking role in the anterior curvature variables of the cornea and smooths the underlying Bowman layer irregularities. In keratoconic patients having CXL, epithelial debridement significantly increased the magnitude of anterior corneal keratometry, astigmatism, and prolateness.

References

1. Lian Y, Shen M, Jiang J, Mao X, Lu P, Zhu D, Chen Q, Wang J, Lu F. (2013). Vertical and horizontal thickness profiles of the corneal epithelium and Bowman’s layer after orthokeratology. Invest Ophthalmol Vis Sci, 54, 691-696, Available at: http://iovs.arvojournals.org/article.aspx?articleid=2189438 Accessed 4-11-2017
2. Ziaei M, Zhang J, Patel DV, McGhee CNJ. Umbilical cord stem cells in the treatment of corneal disease. Surv Ophthalmol. 2017;62:903-905.
3. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. (2008). Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg, 24, 571-581, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592549/pdf/nihms78856.pdf Accessed 4-11-2017
4. Patel S, Marshall J, Fitzke FW III. Refractive index of the human corneal epithelium and stroma. J Refract Surg. 1995;11:100-105.
5. Simon G, Ren Q, Kervick GN, Parel J-M. Optics of the corneal epithelium. Refract Corneal Surg. 1993;9:42-50.
6. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG. Optical coherence tomography. Science. 1991;254:1178-1181.
7. Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ. (2010). Epithelial, stromal, and total corneal thickness in keratoconus: three-dimensional display with Artemis very-high frequency digital ultrasound. J Refract Surg, 26, 259-271, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655809/pdf/nihms211821.pdf Accessed 4-11-2017
8. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009;25:604-610.
9. Li Y, Tan O, Brass R, Weiss JL, Huang D. (2012). Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology, 119, 2425-2433, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514625/pdf/nihms389040.pdf Accessed 4-11-2017
10. Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB. SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg. 2013;29:173-179. erratum, 234. Available at: http://m1.wyanokecdn.com/04008beb1db87e007e25f657e1766bcb.pdf. Erratum available at: https://www.healio.com/ophthalmology/journals/jrs/2013-4-29-4/%7B58bd59ec-9cf4-4583-9166-a43ec415bfe9%7D/erratum. Accessed November 4, 2017.
11. Kanellopoulos AJ, Asimellis G. (2014). OCT corneal epithelial topographic asymmetry as a sensitive diagnostic tool for early and advancing keratoconus. Clin Ophthalmol, 8, 2277-2287, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242699/pdf/opth-8-2277.pdf Accessed 4-11-2017
12. Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, El Sanharawi M, Basli E, Laroche L, Borderie V. Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus. J Cataract Refract Surg. 2015;41:812-820.
13. Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg. 2009;25:S812-S818.
14. Kanellopoulos AJ, Binder PS. Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial transepithelial PRK and collagen cross-linking: the Athens protocol. J Refract Surg. 2011;27:323-331.
15. Ziaei M, Barsam A, Shamie N, Vroman D, Kim T, Donnenfeld ED, Holland EJ, Kanellopoulos J, Mah FS, Randleman JB, Daya S, Güell J., for the ASCRS Cornea Clinical Committee. (2015). Reshaping procedures for the surgical management of corneal ectasia. J Cataract Refract Surg, 41, 842-872, Available at: https://pdfs.semanticscholar.org/ca8d/2671b5df568ed9b175cfa7de97fe03b7e819.pdf Accessed 4-11-2017
16. Touboul D, Trichet E, Binder PS, Praud D, Seguy C, Colin J. Comparison of front-surface corneal topography and Bowman membrane specular topography in keratoconus. J Cataract Refract Surg. 2012;38:1043-1049.
17. Krumeich JH, Daniel J, Knülle A. Live-epikeratophakia for keratoconus. J Cataract Refract Surg. 1998;24:456-463.
18. Yağcı R, Kulak AE, Güler E, Tenlik A, Gürağaç FB, Hepşen İ.F. Comprasion of anterior segment measurments with a dual Scheimpflug placido corneal topographer and a nem partial coherence interferometer in keratoconic eyes. Cornea. 2015;34:1012-1018.
19. Meyer JJ, Gokul A, Vellara HR, Prime Z, McGhee CNJ. Repeatability and agreement of Orbscan II, Pentacam HR, and Galilei tomography systems in corneas with keratoconus. Am J Ophthalmol. 2017;175:122-128.
20. Feng Y, Varikooty J, Simpson TL. Diurnal variation of corneal and corneal epithelial thickness measured using optical coherence tomography. Cornea. 2001;20:480-483.
21. Haque S, Jones L, Simpson T. (2008). Thickness mapping of the cornea and epithelium using optical coherence tomography. Optom Vis Sci, 85, E963-E976, Available at: http://journals.lww.com/optvissci/Fulltext/2008/10000/Contrast_Sensitivity_Function_in_Patients_with.14.aspx Accessed 4-11-2017
22. Huang J, Ding X, Savini G, Pan C, Feng Y, Cheng D, Hua Y, Hu X, Wang Q. A Comparison between Scheimpflug imaging and optical coherence tomography in measuring corneal thickness. Ophthalmology. 2013;120:1951-1958.
23. Randleman JB, Lynn MJ, Perez-Straziota CE, Weissman HM, Kim SW. Comparison of central and peripheral corneal thickness measurements with scanning-slit, Scheimpflug and Fourier-domain ocular coherence tomography. Br J Ophthalmol. 2015;99:1176-1181.
24. Zipper S, Manns F, Fernandez V, Sandadi S, Ho A, Parel J-M., 2001. Corneal modeling using conic section fits of PAR corneal topography system measurements. In: Manns F, Söderberg PG, Ho A, editors., Society of Photo-Optical Instrumentation Engineers. Ophthalmic Technologies XI. Proceedings SPIE 4245, Bellingham, WA, pp. 107-112.
25. 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;42:1190-1197.
26. Gatinel D, Racine L, Hoang-Xuan T. Contribution of the corneal epithelium to anterior corneal topography in patients having myopic photorefractive keratectomy. J Cataract Refract Surg. 2007;33:1860-1865.
27. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. (2010). Epithelial thickness after hyperopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg, 26, 555-564, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492162/pdf/nihms-695885.pdf Accessed 4-11-2017
28. Kanellopoulos AJ, Aslanides IM, Asimellis G. (2012). Correlation between epithelial thickness in normal corneas, untreated ectatic corneas, and ectatic corneas previously treated with CXL; is overall epithelial thickness a very early ectasia prognostic factor? Clin Ophthalmol, 6, 789-800, Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373227/pdf/opth-6-789.pdf Accessed 4-11-2017
29. Reinstein DZ, Archer TJ, Gobbe M. Improved effectiveness of transepithelial PTK versus topography-guided ablation for stromal irregularities masked by epithelial compensation. J Refract Surg. 2013;29:526-533.
30. Reinstein DZ, Archer TJ, Gobbe M. (2014). Rate of change of curvature of the corneal stromal surface drives epithelial compensatory changes and remodeling [letter]. J Refract Surg, 30, 800-802, reply by AJ Kanellopoulos, G Asimellis, 802–805. Available at: https://www.healio.com/ophthalmology/journals/jrs/2014-12-30-12/%7B34c6a8ea-5653-45d8-afc8-2faef52a7905%7D/rate-of-change-of-curvature-of-the-corneal-stromal-surface-drives-epithelial-compensatory-changes-and-remodeling Accessed 4-11-2017
31. Reinstein DZ, Gobbe M, Archer TJ, Couch D. Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia. J Refract Surg. 2011;27:356-363.
32. Manns F, Fernandez V, Zipper S, Sandadi S, Hamaoui M, Ho A, Parel J-M. Radius of curvature and asphericity of the anterior and posterior surface of human cadaver crystalline lenses. Exp Eye Res. 2004;78:39-51.
33. Vinciguerra P, Camesasca FI. Custom phototherapeutic keratectomy with intraoperative topography. J Refract Surg. 2004;20:S555-S563.

Disclosures

None of the authors has a financial or proprietary interest in any material or method mentioned.

© 2018 by Lippincott Williams & Wilkins, Inc.