Epithelial Thickness Mapping Research Articles

Spectral-Domain Optical Coherence Tomography Epithelial and Flap Thickness Mapping in Femtosecond Laser–Assisted In Situ Keratomileusis

To evaluate the change of epithelial and flap thickness after femtosecond laser-assisted in situ keratomileusis (LASIK) using spectral-domain optical coherence tomography (SD OCT) in correlation with the spherical equivalent refraction treated and clinical outcomes. Prospective, randomized, contralateral-eye study. Forty myopic eyes underwent LASIK using an excimer laser with refraction ranging from -1.00 to -7.25 diopters (mean -3.25±1.9). Flap creation was randomized between eyes, using the IntraLASE FS60 laser (IL) in 1 eye and WaveLight FS200 laser (FS) in the contralateral eye. SD OCT was used to evaluate the epithelial and flap thickness profiles and corneal power preoperatively and at 1 week and 1, 3, and 9 months postoperatively. Manifest and wavefront refractions were performed at each postoperative visit. Statistically significant epithelial thickening was observed in both IL and FS groups as early as 1 month postoperatively (P=.033 and P=.042), but this stabilized between 3 (P=.042 and P=.035) and 9 months (P=.043 and P=.041). Femtosecond-LASIK flaps were thicker in the IL group in comparison to the FS group at 3 and 9 months postoperatively (P=.003 and P=.005, respectively). There was a statistically significant correlation between the magnitude of preoperative myopic refraction and the central epithelial thickness at 1, 3, and 9 months (Pearson correlation coefficients 0.485, 0.587 and 0.576) (P=.0021, P=.0010, and P=.0011), respectively. SD OCT corneal power maps showed steepening at 3 and 9 months along with mild myopic shift. Progressive epithelial and flap thickening with increased corneal power were observed after femtosecond laser-assisted in situ keratomileusis for myopia with consequent stabilization between 3 to 9 months postoperatively. The magnitude of epithelial and flap thickness remodeling correlated to the preoperative myopic refractive error.

Erratum

To evaluate epithelial thickness profile changes following myopic femtosecond laser-assisted LASIK in relation to the degree of myopia corrected, evaluated with a spectral-domain anterior-segment optical coherence tomography system. Sixty-one consecutive cases were observed for corneal epithelial thickness distribution preoperatively and at 1 day, 1 week, 1 month, and 1 year postoperatively. Epithelial thickness mapping was obtained with a spectral-domain optical coherence tomography system (Optovue Inc., Fremont, CA). Descriptive statistics investigated epithelial thickness at the central 2-mm area, the mean over the central 6-mm area, and mid-peripherally at the 5-mm ring area. Preoperatively, the pupil center epithelial thickness was 51.67 ± 2.57 μm (range: 45 to 56 μm), mean was 51.76 ± 2.66 μm (range: 45 to 57 μm), and mid-periphery was 51.78 ± 2.71 μm (range: 46 to 57 μm). Compared to the preoperative values, the epithelial thickness for the center, mean, and mid-periphery was −0.30, +1.07, and +1.35 μm at 1 week, +1.58, +2.88, and +3.31 μm at 1 month (P = .0036, < .001, and < .001), and +1.42, +2.90, and +3.19 μm at 1 year postoperatively (P = 0.146, < .001, and < .001), respectively. The correlation analysis between the epithelial thickness increase and the spherical equivalent of myopic correction showed a trend toward epithelial thickness increase with the amount of myopic ablation, particularly at the mid-peripheral 5-mm area. In this comprehensive study of postoperative corneal epithelial thickness remodeling following femtosecond laser-assisted myopic LASIK correction, an increase at the 1-month and up to 1-year postoperative interval suggested postoperative epithelial activity in connection to the extent of ablation.

Pachymetry Map of Corneal Epithelium in Children Wearing Orthokeratology Contact Lenses

Purpose: To study the pachymetry map of the corneal epithelium in children wearing orthokeratology lenses automatically generated by a Fourier-domain optical coherence tomography.Materials and Method: The study was conducted on 60 children who had been fitted with myopic orthokeratology lenses. Patients were divided into two groups according to the duration of OK lens treatment (group 1: ≤14 days, n = 28; group 2: >14 days, n = 32). The control group consisted of 44 children. An FD-OCT device with a pachymetry module was used to map the central 6-mm corneal epithelial thickness. An epithelial thickness map was automatically generated and divided into three zones: central 2 mm, paracentral 2 to 5 mm (P1) and mid-peripheral 5 to 6 mm (P2). The average epithelial thickness of central (C), the temporal (T1), nasal (N1), superior (S1) and inferior (I1) sectors of P1, and the temporal (T2), nasal (N2), superior (S2) and inferior (I2) sectors of P2 were recorded and compared. The minimum and maximum points of epithelial thickness across the map were also recorded. Munnerlyn’s formula was used to model the expected change in refractive error based on Δ(Max-Min) (Δ(Max-Min) = (Max-Min)study-(Max-Min) mean of control).Results: The central epithelial thickness was significantly different between individual groups and a significant difference from the control (Group 0) was seen in each treatment group. Both the epithelial thickness measurements of T1 and I1 were thinnest in Group 1. Both the epithelial thickness measurements of S2 and I2 were thickest in Group 2. The difference between maximum and minimum thickness was significantly different between groups with the largest effect in Group 2. The refractive changes predicted by Munnerlyn’s formula were less than the actual refractive changes measured in both study groups.Conclusions: The epithelial thickness map automatically generated by FD-OCT can provide regional information about corneal epithelium thickness following overnight wearing of OK lenses.

In Vivo 3-Dimensional Corneal Epithelial Thickness Mapping as an Indicator of Dry Eye: Preliminary Clinical Assessment

To evaluate in vivo epithelial thickness in dry eye by anterior segment optical coherence tomography. Observational, retrospective case-control study. Two age-matched groups of female subjects, 70 eyes each, age ≈ 55 years, were studied in clinical practice setting: a control (unoperated, no ocular pathology) and a dry eye group (clinically confirmed dry eye, unoperated and no other ocular pathology). Corneal epithelium over the entire cornea was topographically imaged via a novel anterior segment optical coherence tomography (AS-OCT) system. Average, central, and peripheral epithelial thickness as well as topographic epithelial thickness variability were measured. For the control group, central epithelial thickness was 53.0 ± 2.7 μm (45-59 μm). Average epithelium thickness was 53.3 ± 2.7 μm (46.7-59.6 μm). Topographic thickness variability was 1.9 ± 1.1 μm (0.7-6.1 μm). For the dry eye group, central epithelial thickness was 59.5 ± 4.2 μm (50-72 μm) and average thickness was 59.3 ± 3.4 μm (51.4-70.5 μm). Topographic thickness variability was 2.5 ± 1.5 μm (0.9-6.9 μm). All pair tests of respective epithelium thickness metrics between the control and dry eye group show statistically significant difference (P < .05). This study, based on very user-friendly, novel AS-OCT imaging, indicates increased epithelial thickness in dry eyes. The ease of use and the improved predictability offered by AS-OCT epithelial imaging may be a significant clinical advantage. Augmented epithelial thickness in the suspect cases may be employed as an objective clinical indicator of dry eye.

Refractive and Topographic Errors in Topography-guided Ablation Produced by Epithelial Compensation Predicted by 3D Artemis VHF Digital Ultrasound Stromal and Epithelial Thickness Mapping

To describe and quantify the errors inherent to topography-guided ablation of irregular corneas due to natural epithelial thickness compensatory remodeling. Artemis very high-frequency (VHF) digital ultrasound scanning (ArcScan Inc) was performed on a cornea that had undergone radial keratotomy with inferior and superior trapezoidal keratotomies, resulting 27 years later in high irregular astigmatism (+6.50 -8.00 × 101) and severe loss of corrected distance visual acuity (CDVA) to 20/50. The epithelial thickness profile was highly irregular, masking a significant proportion of the true stromal irregularity from front corneal surface topography, which would have resulted in significant inaccuracies had a topography-guided ablation been performed. The stromal ablation pattern of a transepithelial phototherapeutic keratectomy (PTK) ablation was modeled, which appeared logically to reduce the areas of abnormal stromal surface elevation and resembled a hyperopic astigmatic ablation of approximately 3.50 diopters of cylinder. Artemis-assisted transepithelial PTK was performed to target the stromal irregularity masked by epithelium. Artemis-assisted transepithelial PTK induced a refractive change similar to that predicted (+2.24 -3.97 × 120), demonstrating the refractive shift produced by the epithelium. The epithelial thickness profile became relatively regular and CDVA returned to 20/20⁻². Two topography wavefront-guided ablations were performed to correct the remaining topographic irregularity and refractive error, resulting in a near plano refraction, significantly lower higher order aberrations, and CDVA of 20/20⁺². A knowledge of stromal surface shape and power shift produced by epithelial thickness profile alterations after corneal surgery has the potential of improving the efficacy and safety of custom corneal ablation.

Corneal Epithelial Thickness Mapping by Fourier-Domain Optical Coherence Tomography in Normal and Keratoconic Eyes

To map the corneal epithelial thickness with Fourier-domain optical coherence tomography (OCT) and to develop epithelial thickness-based variables for keratoconus detection. Cross-sectional observational study. One hundred forty-five eyes from 76 normal subjects and 35 keratoconic eyes from 22 patients. A 26,000-Hz Fourier-domain OCT system with 5-μm axial resolution was used. The cornea was imaged with a Pachymetry + Cpwr scan pattern (6-mm scan diameter, 8 radials, 1024 axial-scans each, repeated 5 times) centered on the pupil. Three scans were obtained at a single visit in a prospective study. A computer algorithm was developed to map the corneal epithelial thickness automatically. Zonal epithelial thicknesses and 5 diagnostic variables, including minimum, superior-inferior (S-I), minimum-maximum (MIN-MAX), map standard deviation (MSD), and pattern standard deviation (PSD), were calculated. Repeatability of the measurements was assessed by the pooled standard deviation. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Descriptive statistics, repeatability, and AUC of the zonal epithelial thickness and diagnostic variables. The central, superior, and inferior epithelial thickness averages were 52.3 ± 3.6 μm, 49.6 ± 3.5 μm, and 51.2 ± 3.4 μm in normal eyes and 51.9 ± 5.3 μm, 51.2 ± 4.2 μm, and 49.1 ± 4.3 μm in keratoconic eyes. Compared with normal eyes, keratoconic eyes had significantly lower inferior (P = 0.03) and minimum (P<0.0001) corneal epithelial thickness, greater S-I (P = 0.013), more negative MIN-MAX (P<0.0001), greater MSD (P<0.0001), and larger PSD (P<0.0001). The repeatability of the zonal average, minimum, S-I, and MIN-MAX epithelial thickness variables were between 0.7 and 1.9 μm. The repeatability of MSD was better than 0.4 μm. The repeatability of PSD was 0.02 or better. Among all epithelial thickness-based variables investigated, PSD provided the best diagnostic power (AUC = 1.00). Using an PSD cutoff value of 0.057 alone gave 100% specificity and 100% sensitivity. High-resolution Fourier-domain OCT mapped corneal epithelial thickness with good repeatability in both normal and keratoconic eyes. Keratoconus was characterized by apical epithelial thinning. The resulting deviation from the normal epithelial pattern could be detected with very high accuracy using the PSD variable. Proprietary or commercial disclosure may be found after the references.

Anterior Segment Biometry: A Study and Review of Resolution and Repeatability Data

To obtain comparable resolution and repeatability data for a selection of anterior segment imaging devices. A standard letter of request was sent in May 2008 to each device manufacturer requesting resolution and repeatability data for its device to be provided according to specific definitions and protocol; if this was not already published in the peer-reviewed domain, compliant raw data were required. Where applicable, repeatability data were reported for corneal vertex corneal thickness; epithelial and flap thickness; minimum corneal thickness; corneal, epithelial and flap thickness mapping for the central 6-mm diameter; minimum residual stromal thickness; angle-to-angle diameter; sulcus-to-sulcus diameter; and anterior chamber depth. To summarize published repeatability data, a complete review of the peer-reviewed literature waas performed. Nine of the 13 manufacturers contacted agreed to take part and provided the data requested: Pentacam HD (Oculus Optikgeräte GmbH), Galilei (Ziemer), Visante OCT (Carl Zeiss Meditec), SL-OCT (Haag-Streit), RTVue (Optovue), Artemis (ArcScan), Vumax (Sonomed), HiScan (Opticon), and Eye Cubed (Ellex/Innovative). Only one (Carl Zeiss Meditec) of 9 manufacturers was able to provide the data directly upon request, without performing a prospective study. Five of the 9 manufacturers were able to provide a complete set of repeatability data for all parameters measurable with their device; the remaining 4 manufacturers admitted that repeatability of some parameters was unknown. Both literature and manufacturers' data on file were lacking and required the study to be performed. This report provides an imperfect, but most comprehensive to date, resolution and repeatability data review of biometric devices intended for surgical planning.

Epithelial Thickness Profile as a Method to Evaluate the Effectiveness of Collagen Cross-Linking Treatment After Corneal Ectasia

To illustrate the hypothesis that epithelial thickness profile maps could be a useful adjunct to topography in monitoring patients after corneal collagen cross-linking (CXL) treatment. Epithelial thickness profile in vivo was measured by Artemis very high-frequency (VHF) digital ultrasound scanning (ArcScan Inc) across the central 10-mm corneal diameter of a patient before collagen CXL for corneal ectasia after LASIK and at intervals up to 2 years later. Manifest refraction, corneal topography, and corneal front-surface aberrations were also monitored. Epithelial thickness changes were cross-correlated with corneal topography changes and corneal front-surface aberration changes. Corneal collagen CXL appeared effective in halting the progression of corneal ectasia. Manifest refraction showed a reduction in spherical equivalent over time after CXL in both eyes. Corneal topography demonstrated stable central keratometry in both eyes. Corneal wavefront aberrations demonstrated a reduction of higher order root-mean-square coma and spherical aberration in both eyes. The epithelial thickness profile was altered, with a slight reduction of the area of epithelial thinning and decreased peripheral thickening. This resulted in minimizing the difference between the thinnest and thickest epithelium and might indicate an improvement of the condition. There were no significant changes in minimum stromal and minimum corneal thicknesses. Epithelial thickness maps provide useful information for monitoring the progression of corneal ectasia after corneal collagen CXL, showing in this case, at least no further progression of the ectasia.

Stability of LASIK in Topographically Suspect Keratoconus Confirmed Non-keratoconic by Artemis VHF Digital Ultrasound Epithelial Thickness Mapping: 1-year Follow-up

To determine the 1-year stability of LASIK in corneas with topographic suspect keratoconus confirmed as non-keratoconic by epithelial thickness mapping. This was a retrospective case/control comparative study. Eyes suspected of keratoconus using criteria based mainly on Atlas (Carl Zeiss Meditec AG) and Orbscan II (Bausch & Lomb) topography were scanned by Artemis very high-frequency digital ultrasound (ArcScan Inc). Keratoconus was confirmed if the epithelial thickness profile showed relative epithelial thinning coincident with an eccentric posterior elevation best-fit sphere apex. Laser in situ keratomileusis was performed in all eyes where keratoconus was excluded by finding relatively thicker epithelium or not finding localized thinning over the topographically suspected cone. Patients were followed for 1 year after LASIK. A control group was generated matched within 0.50 diopter (D) for sphere, cylinder, and spherical equivalent refraction (SEQ) to compare refractive stability. The average change in SEQ between 3 and 12 months was -0.10+/-0.30 D for the suspect keratoconus group and -0.10+/-0.28 D for controls. No statistically significant difference in shift from 3 months to 12 months in SEQ or cylinder between groups was noted. No statistically significant change in best spectacle-corrected visual acuity between groups was noted, with no eye losing 2 lines and 5% in the suspect keratoconus group and 2% of controls losing 1 line. No cases of ectasia were observed in either group. Suspect keratoconus, confirmed to be non-keratoconic by epithelial thickness profile criteria demonstrated equal stability to control eyes 1 year after LASIK. Epithelial thickness profiles may enable LASIK to be performed in eyes that would otherwise have been excluded due to topographic suspect keratoconus. Further follow-up is being carried out.

Thickness Mapping of the Cornea and Epithelium Using Optical Coherence Tomography

To measure corneal and epithelial thickness across four meridians using Optical Coherence Tomography (OCT) and to compare these measurements between normal non-lens wearers (NLW), rigid gas permeable (RGP) lens wearers, and RGP-wearing keratoconics (KC). Both eyes of 60 subjects were measured (20 NLW, nine female:11 male, 27.6 +/- 5.9 years; 20 RGP, 20 female, 23.9 +/- 7.6 years; and 20 KC, seven female:13 male, 32.4 +/- 8.1 years). A customized fixation target employing LEDs in eight directions of gaze was attached to the OCT and corneal images obtained. Raw OCT scans were analyzed to yield values for corneal and epithelial thickness and color-coded maps were compiled. Central corneal thickness (CCT) was thinnest in KC (447 +/- 68 microm) and similar between RGP (518 +/- 32 microm; pKC < 0.001) and NLW (517 +/- 21 microm) (p(KC) < 0.001 NLW pRGP > 0.05). Peripheral corneal thickness in NLW was thickest in the superior temporal and thinnest in the inferior (I) regions (superior temporal(thickest) vs. I(thinnest) p < 0.001). Central epithelial thickness was thinnest in KC (44 +/- 7 microm), followed by RGP (50 +/- 4 microm), then NLW (54 +/- 2 microm) (pKC < 0.001 NLW p(RGP) < 0.05). Central epithelial thickness in the KC group was significantly thinner than in the RGP group (p < 0.001). In the NLW group, peripheral epithelial thickness was thicker (63 +/- 5 microm) than central (p < 0.001) and was thickest in the superior (S) region and thinnest in the inferior (I) region (S(thickest) vs. I(thinnest) p < 0.001). KC epithelium was thinnest in the inferior temporal meridian (42 +/- 5 microm). Thickness of the normal cornea and epithelium was greatest in the superior region. In all groups, the inferior cornea and epithelium was thinnest, and to a greater extent in the KC group.

Epithelial Thickness in the Normal Cornea: Three-dimensional Display With Artemis Very High-frequency Digital Ultrasound

Purpose To characterize the in vivo epithelial thickness profile in a population of normal eyes. Methods An epithelial thickness profile was measured by Artemis 1 (ArcScan Inc) very high-frequency (VHF) digital ultrasound scanning across the central 10-mm diameter of the cornea of 110 eyes of 56 patients who presented for refractive surgery assessment. The average, standard deviation, minimum, maximum, and range of epithelial thickness were calculated for each point in the 10×10-mm Cartesian matrix and plotted. Differences between the epithelial thickness at the corneal vertex and peripheral locations at the 3-mm radius were calculated. The location of the thinnest epithelium was found for each eye and averaged. Correlations of corneal vertex epithelial thickness with age, spherical equivalent refraction, and average keratometry were calculated. Results The mean epithelial thickness at the corneal vertex was 53.4±4.6 µ m, with no statistically significant difference between right and left eyes, and no significant differences in age, spherical equivalent refraction, or keratometry. The average epithelial thickness map showed that the corneal epithelium was thicker inferiorly than superiorly (5.9 µm at the 3-mm radius, P &lt;.001) and thicker nasally than temporally (1.3 µm at the 3-mm radius, P &lt;.001). The location of the thinnest epithelium was displaced on average 0.33 mm temporally and 0.90 mm superiorly with reference to the corneal vertex. Conclusions Three-dimensional thickness mapping of the corneal epithelium demonstrated that the epithelial thickness is not evenly distributed across the cornea; the epithelium was significantly thicker inferiorly than superiorly and significantly thicker nasally than temporally with a larger inferosuperior difference than nasotemporal difference. [ J Refract Surg. 2008;24:571–581.]

Measuring the cornea: the latest developments in corneal topography

Corneal measurement uses Placido-disc topographers and tomographers, creating three-dimensional corneal models from cross-sectional images. Technology includes slit scanning, Scheimpflug imaging, very high frequency ultrasound, and high-speed anterior segment optical coherence tomography. Normative data in the Asian population using the Orbscan, and repeatability information for the 3 and 5-mm zone were reported. Best fit sphere and the thinnest point were not significantly different, but posterior surface elevation was higher using the Orbscan in keratoconic eyes. Pachymetry data from the Pentacam show pattern differences used as keratoconus indices. Scheimpflug imaging identified changes in the posterior surface that were not mirrored by the anterior surface with aging, and may be better for surgical planning than conventional keratometry following excimer treatments. Optical coherence tomography mean central corneal thickness measurements were repeatable; however, mean central epithelial thickness measurements were not. Very high frequency ultrasound can be used successfully to create epithelial and flap thickness maps. Studies reveal specular microscopy measures thinner and less reliable readings than Pentacam and Orbscan. New corneal topographers, such as Scheimpflug imaging, ultrasound and optical coherence tomography have expanded capabilities and precision in measuring the structure of the cornea.