As described by Alfred Vogt in 1921,1 it is known that the corneal epithelium has the ability to alter its thickness profile to compensate for changes in stromal surface curvature to try to reestablish a smooth, symmetrical optical surface. Such compensatory epithelial thickness changes have since been described after myopic excimer laser ablation,2–4 hyperopic excimer laser ablation,5 radial keratotomy,6 orthokeratology,7 and in keratoconus8 and ectasia.9 In cases of irregularly irregular astigmatism, the compensatory mechanism of the epithelium has a significant effect because epithelial thickness changes mask the true curvature of the irregular stromal surface.10–13 Due to this epithelial masking, topography and wavefront measurements cannot provide a diagnosis for the exact anatomy of the pathology that needs correcting (ie, the irregular stromal surface). Therefore, topography-guided or wavefront-guided treatments may lead to a suboptimal treatment.10–13
Where sufficient epithelial compensation has occurred over an irregularly irregular stromal surface, transepithelial phototherapeutic keratectomy (TE-PTK) can be performed to regularize the stromal surface and has been used for years in the repair of refractive surgery complications.11–15 TE-PTK treatments are also used in the treatment of corneal conditions such as recurrent erosion,16,17 corneal dystrophies,17,18 and scarring,19,20 as well as for reducing the cone in keratoconus combined with cross-linking.21,22 The procedure takes advantage of the compensatory nature of the epithelium by using it as a natural masking agent. An excimer laser is used to uniformly ablate epithelial and stromal tissue across a wide diameter of the cornea. Ablation through the thinnest area of epithelium exposes stromal surface peaks and targets isolated stromal ablation onto these areas. Stromal surface irregularities are smoothed as the masking epithelium is progressively ablated.
The objectives of this study were to report the treatment parameters and outcomes of a population of patients treated by TE-PTK and to present a standardized method of performing TE-PTK based on population statistics of preoperative epithelial thickness.
Patients and Methods
This was a retrospective analysis of 41 TE-PTK treatments performed on 31 eyes of 28 patients to treat irregularly irregular astigmatism. All treatments were performed at the London Vision Clinic, London, United Kingdom, by the lead author. Patients recruited included 25 patients presenting with previous refractive surgery that had resulted in complications or impaired vision and 3 patients who had non-iatrogenic corneal irregular astigmatism. Presenting complaints are shown in Table A (available in the online version of this article) and include reduced corrected distance visual acuity (CDVA), ghosting, doubling of vision, halos, glare, star bursts, and blurring. A summary of previous surgery is shown in Table A and included refractive surgery complications (ie, LASIK, photorefractive keratectomy, small incision refractive lenticule extraction, and radial keratotomy), corneal transplantation, corneal trauma, and corneal scarring. In all cases, the purpose of TE-PTK treatment was to regularize and smooth an irregularly irregular stromal surface to improve quality of vision.
Prior to TE-PTK treatment, a full ophthalmic examination was performed according to our standard complex case evaluation protocol as described previously,11–13 which included a three-dimensional Artemis very high-frequency digital ultrasound scan (ArcScan, Inc., Morrison, CO) to provide pachymetric maps of the individual corneal layers including the epithelial thickness over a 10-mm diameter. The repeatability of central epithelial thickness measurement with the Artemis has previously been shown to be 0.58 μm.23 Epithelial thickness maps allow for Artemis-assisted TE-PTK treatments using a technique called digital subtraction pachymetry (DSP)11–13 as demonstrated in Figure 1, in which the breakthrough pattern and remaining epithelium at regular lamellar depths of TE-PTK ablation are simulated.
Artemis digital subtraction pachymetry simulation (ArcScan, Inc., Morrison, CO) of the pattern of remaining epithelium that would be expected after increasing transepithelial phototherapeutic keratectomy (TE-PTK) ablations after (A) 45 μm, (B) 55 μm, and (C) 75 μm. The white represents the regions where all of the epithelium would have been ablated after the labeled TE-PTK ablation, and hence the regions where ablation of stromal tissue would occur. During the procedure, the cornea was examined (as shown in the intraoperative photograph, [D]) and the areas of exposed stroma were compared to the Artemis simulated maps. At this point, the ablation depth for the subsequent TE-PTK ablations can be calibrated for each eye individually. Further TE-PTK ablations are then performed in a stepwise fashion until the intended end-point is reached. (E) The intraoperative photograph in this example shows the pattern of remaining epithelium was similar to the predicted pattern.
All of the Artemis-assisted TE-PTK procedures were performed using the MEL80 excimer laser (Carl Zeiss Meditec, Jena, Germany). The PTK ablations were applied over an 8.0-mm diameter zone in 35 treatments (85%) and over smaller 5.0- to 7.0-mm diameter zones in the remaining 6 cases (15%). The first phase of TE-PTK treatment ablation for each case was planned to expose a small area of stroma in the region of the thinnest epithelium. The initial ablation depth data entry into the MEL80 excimer laser was calculated using a conversion factor of between 1.07 and 1.49 times the intended depth based on our previous Artemis-assisted TE-PTK procedure experience. After the initial ablation, the epithelial DSP maps were compared to the observed epithelial breakthrough pattern to estimate the actual achieved ablation depth. This allowed the conversion factor used for subsequent ablations to be calibrated individually for each case. Based on the remaining epithelium thickness, ablations continued to be applied in steps of 10 to 20 μm with the final goal of removing almost all of the epithelium up to the maximum thickness. In cases with localized irregularities, the epithelium was not removed to its full thickness to conserve stromal tissue.
In approximately half of the cases, a series of “wet” PTK ablations were then performed to further smooth the surface, specifically targeting fine irregularities such as microfolds.13 The “wet” PTK ablations were done by first flooding the cornea with balanced salt solution, followed immediately by a 6-second, 8-mm PTK ablation (20 μm on the MEL80 excimer laser). The balanced salt solution acts as a masking agent, in a similar way to the epithelium previously, and naturally spreads across the surface, leaving the ridges of any microfolds closer to the surface. The shockwaves of the excimer laser pulse expose the peaks of the microfolds through the fluid surface, allowing the sharper extrusions to be ablated in isolation from the rest of the stromal surface. After 6 seconds, surface tension of the balanced salt solution begins breaking up so further ablation was aborted. This process was repeated until the dried surface was visibly smooth.
In addition, selected patients had standard refractive, topography-guided,24 or wavefront-guided11 ablations immediately following TE-PTK. Complimentary treatments were performed after the TE-PTK stage of the procedure to account for a refractive shift that was expected based on the DSP predicted stromal ablation pattern to correct a patient’s preoperative refractive error or to correct large-scale global irregularities that were only minimally masked by epithelium.11,14,15 In 10 eyes, a single TE-PTK treatment did not result in adequate regularization of the stromal surface, and a second TE-PTK was performed at a later date after the epithelium had remodeled, compensating for the remaining stromal irregularities.
Analysis of Visual Outcomes
For the analysis of visual outcomes, the population was divided into two groups defined as having either TE-PTK only (TE-PTK only group) with no intended correction of refraction or TE-PTK and additional refractive, topography-guided, or wavefront-guided ablation (TE-PTK with refractive treatment group). Group demographics and preoperative refractive data are shown in Table 1. All outcomes data were collected at 12 months postoperatively and stability of spherical equivalent refraction was assessed at 1 week and 1, 3, 6, and 12 months postoperatively. The analysis for the TE-PTK only group included the preoperative and postoperative uncorrected distance visual acuity (UDVA), change in CDVA, change in UDVA, spherical equivalent refractive change, preoperative and postoperative refractive astigmatism, and stability of spherical equivalent refraction. The analysis for the TE-PTK with refractive treatment group included the preoperative and postoperative UDVA, change in CDVA, scatter plot of attempted versus achieved spherical equivalent refraction, spherical equivalent refractive accuracy, preoperative and postoperative refractive astigmatism, and stability of spherical equivalent refraction.
Demographic and Refractive Data Before and After TE-PTK
Analysis of Epithelial Thickness
Minimum and maximum epithelial thicknesses in the location of the irregularity were recorded (ie, mean, standard deviation, and range) before and at least 3 months after surgery when most of the epithelial remodeling has already taken place.4 The difference between the minimum and maximum epithelial thicknesses in the location of the irregularity was calculated before and after surgery. This within-eye epithelial thickness range was used as a parameter to measure the extent of the stromal surface irregularity on the basis that a higher degree of epithelial compensation occurs in a more irregular stromal surface. The change in within-eye epithelial thickness range was calculated to quantify the change in stromal surface irregularities achieved by the TE-PTK procedure. The change in epithelial thickness range was analyzed for the TE-PTK only group alone because changes in epithelial thickness range can be attributed solely to the effect of the TE-PTK treatment. Additional refractive ablation profiles included in treatments are associated with postoperative epithelial compensation unrelated to TE-PTK and therefore were not as useful in defining the efficacy of TE-PTK.
Group demographics and visual outcomes of the TE-PTK only group (n = 30) 12 months postoperatively are displayed in Table 1 and Figure 2. The visual outcomes of the TE-PTK with refractive treatment group (n = 11) 12 months postoperatively are displayed in Table 1 and Figure 3 (one eye was excluded from these results because the patient lived abroad and was unable to attend follow-up after 1 week).
Visual outcomes for the transepithelial phototherapeutic keratectomy (TE-PTK) only group: (A) preoperative and postoperative cumulative uncorrected distance visual acuity (UDVA), (B) within eye change in corrected distance visual acuity (CDVA), (C) within eye change in UDVA, (D) within eye spherical equivalent refractive change, (E) preoperative and postoperative refractive astigmatism, and (F) stability of spherical equivalent refraction over time.
Visual outcomes of the transepithelial phototherapeutic keratectomy (TE-PTK) with refractive treatment group: (A) preoperative and postoperative cumulative uncorrected distance visual acuity (UDVA), (B) within eye change in corrected distance visual acuity (CDVA), (C) spherical equivalent refraction attempted against that achieved, (D) spherical equivalent refractive accuracy, (E) preoperative and postoperative refractive astigmatism, and (F) stability of spherical equivalent refraction over time.
Twenty-eight of 30 treatments in the TE-PTK only group had both preoperative and postoperative epithelial thickness measurements. There were 11 treatments in the TE-PTK with refractive treatment group (5 refractive, 3 topographic, and 3 wavefront), of which 9 had both preoperative and postoperative epithelial thickness measurements. Table A displays the preoperative and postoperative minimum and maximum epithelial thicknesses and epithelial thickness ranges before and after treatment, as well as the change in epithelial thickness range for both groups. Figure 4 shows the change in epithelial thickness range for the TE-PTK only group.
Boxplot displaying the Artemis VHF digital ultrasound (ArcScan, Inc., Morrison, CO) epithelial thickness range before and after transepithelial phototherapeutic keratectomy (TE-PTK) of the TE-PTK only group. The marked reduction in epithelial thickness range indicates a lesser degree of epithelial compensation and is interpreted as a reduction in stromal surface irregularity.
The preoperative minimum and maximum epithelial thicknesses for the entire population are displayed in Table A. Figure 5 shows the ranges of preoperative minimum and maximum epithelial thicknesses, with the “therapeutic window” between the highest minimum value and the lowest maximum value shaded in green. One eye had a preoperative minimum epithelial thickness of 54 μm and was considered an outlier. The next highest minimum value was 51 μm, so an effective “therapeutic window” excluding the 54 μm outlier is shaded in light green.
Boxplot displaying preoperative Artemis VHF digital ultrasound (ArcScan, Inc., Morrison, CO) thinnest and thickest epithelium for the entire population. The “therapeutic window” is defined as between the population’s maximum thinnest epithelium and minimum thinnest epithelium. Dark green indicates the narrow “therapeutic window,” including an anomalously high thinnest epithelium, and light green indicates a wider “therapeutic window” without this outlier.
This study has demonstrated that TE-PTK can be a safe and effective method of improving quality of vision by reducing stromal surface irregularities. The majority of patients in both groups experienced a gain in CDVA, with only a single eye (2.4%) losing one line and no eyes losing two or more lines. Stromal surface irregularities were reduced as shown by an overall reduction of the epithelial thickness range following TE-PTK treatment. Analysis of our population database of preoperative epithelial thicknesses indicates a “therapeutic window” that can be used in planning an initial ablation depth that would ensure breakthrough of the minimum epithelial thickness without entirely removing the epithelium and that preserves stromal tissue. This initial target ablation window can be used regardless of the excimer laser device and without direct epithelial thickness measurements.
The purpose of TE-PTK treatments is not to correct refractive error but instead to reduce visually disturbing stromal surface irregularities and improve quality of vision. This was reflected in the visual outcomes of the TE-PTK only group because there was a gain of one or more lines of CDVA in 55% of eyes. It is important to note that the ablation profile defined by the epithelial compensation pattern has the effect of inducing a myopic shift in some cases and a hyperopic shift in others; there was a change in spherical equivalent refraction of more than 1.00 D in 40% of eyes distributed relatively evenly between hyperopic (23%) and myopic (17%) shifts. There was an associated change in UDVA with a gain of one or more lines of UDVA in 42% of eyes and loss in 48% of eyes. In this series, astigmatism remained relatively unchanged.
For the correction of refractive error or to treat large-scale global irregularities, additional procedures are required. These can be applied directly after the TE-PTK removal of the epithelium as standard refractive, wavefront-guided, or topography-guided photorefractive keratectomy treatments. In the TE-PTK with refractive treatment group, the efficacy of the TE-PTK segment was demonstrated as a gain of one or more lines of CDVA in 64% of eyes and no loss in any eyes. Despite the unintended refractive shift associated with TE-PTK, it is still possible to correct refractive error as part of the same procedure in cases where the epithelial thickness profile was deemed to be refractively neutral. The observed presence of two refractive outliers (18%) demonstrates the potential refractive shift due to the unpredicted refractive lenticular mask effect of the epithelium. Nevertheless, the accuracy of refractive treatments with TE-PTK was reasonably good, although these were cases preselected as having apparently refractively neutral epithelial thickness profiles. This agrees with the results previously reported by Chen et al.14,15 for combined TE-PTK and topography-guided treatments.
Due to the compensatory masking effect of the epithelium, the epithelial thickness range between the thickest and thinnest areas is linked to the degree of stromal irregularity. In the TE-PTK only group, a reduction in epithelial thickness range was achieved in 89% of treatments, with a mean change of −12 ± 10 μm (range: −31 to +5 μm), demonstrating the improvement in the stromal surface irregularity.
The reason for the variability in effectiveness is that the epithelium can only compensate for a certain portion of stromal surface irregularities, governed by rate of change of curvature of the stromal surface as previously described.10–12 Eyes with a highly irregular stromal surface topography and high rate of change of curvature will produce a greater degree of epithelial compensation. In these cases, the effectiveness of TE-PTK is maximized and a single treatment can almost completely smooth the irregular stromal surface.13 However, in most cases, the epithelial compensation has reached its maximum limit, meaning that a single TE-PTK treatment may not completely smooth the stromal surface and further treatment may be required.13 In the TE-PTK only group, there were 2 eyes (patients 9 and 12, left eye) in which there was apparently no improvement in the stromal surface irregularity because the epithelial thickness range was actually slightly increased after the first TE-PTK treatment. However, the epithelial thickness range was subsequently improved by a second treatment after regrowth and recompensation by the epithelium. In these cases, the epithelium could not compensate for the full depth of the irregularities, meaning that although the first TE-PTK treatment had reduced the irregularity, it was still deep enough for the epithelium to compensate by the same amount as before treatment. There were 10 eyes that underwent two or more treatments and these had a mean preoperative epithelial thickness range of 45 ± 19 μm (range: 19 to 79 μm) before their first TE-PTK, significantly higher than for all other treatments, which had a mean preoperative epithelial thickness of 37 ± 17 μm (range: 12 to 95 μm), demonstrating that eyes requiring multiple procedures were associated with a more irregular stromal surface.
In the Artemis-assisted TE-PTK procedure used in the current study, the goal of the initial TE-PTK ablation was to break through the epithelium in the region where it was thinnest to expose the peaks in the stromal surface to be ablated. The secondary goal was to avoid removing the full thickness of epithelium because any ablation after complete removal of the epithelium will have no effect on stromal surface irregularities. This method therefore avoids wasting stromal tissue. In the current study, we have identified a “therapeutic window” of 51 to 60 μm, so an initial ablation depth of 55 μm should achieve breakthrough but not complete removal of the epithelium (although this should be adjusted to take into account the epithelial ablation rate of the excimer laser being used). Subsequent ablations can be performed in 10- to 20-μm steps, chosen intraoperatively after reviewing the coverage and pattern of epithelium remaining after each ablation. During this process, the pattern of remaining epithelium can be observed to identify the areas where the stroma is being ablated. The pattern of stromal ablation can then be correlated to corneal topography and wavefront to gain an understanding of the stromal surface irregularity being treated and evaluate potential postoperative changes. These stepwise ablations can be continued until the epithelium is completely removed or is restricted to an isolated area.
Ideally, an epithelial thickness map would be obtained before surgery to diagnose and assess the stromal surface irregularities, as well as to be used as a guide during the procedure. Aside from VHF digital ultrasound, epithelial thickness maps have been described using the RTVue OCT (OptoVue, Inc., Fremont, CA), which has a repeatability of 0.7 μm,25 but epithelial thickness measurements are restricted to 3-μm steps. RTVue epithelial thickness maps are also currently limited to measure within a 6-mm diameter, and include the tear film (which can vary), meaning it is not a true measurement of the epithelium. The signal-to-noise ratio may also be reduced even further in eyes after PRK where Bowman’s layer has been removed.
Artemis-assisted TE-PTK was successful in reducing stromal surface irregularities and improving the quality of vision in cases of irregularly irregular astigmatism due to a wide variety of corneal conditions and refractive surgical complications. A preoperative epithelial thickness measurement acts as a mirror template for the stromal surface irregularity due to the compensatory mechanism of the epithelium. An epithelial thickness map is also useful for ensuring the accuracy of the ablation depth during a TE-PTK procedure. Refractive accuracy of TE-PTK treatments could be improved by a preoperative measurement of the refractive power of the epithelium. Finally, the epithelial thickness range can be used as a parameter for assessing the degree of stromal surface irregularity and evaluating the efficacy of a stromal surface smoothing procedure such as TE-PTK.
- Vogt A. Textbook and Atlas of Slit Lamp Microscopy of the Living Eye. Bonn, Germany: Wayenborgh Editions; 1981.
- Gauthier CA, Holden BA, Epstein D, Tengroth B, Fagerholm P, Hamberg-Nystrom H. Role of epithelial hyperplasia in regression following photorefractive keratectomy. Br J Ophthalmol. 1996;80:545–548. doi:10.1136/bjo.80.6.545 [CrossRef]
- Reinstein DZ, Srivannaboon S, Gobbe M, et al. Epithelial thickness profile changes induced by myopic LASIK as measured by Artemis very high-frequency digital ultrasound. J Refract Surg. 2009;25:444–450. doi:10.3928/1081597X-20090422-07 [CrossRef]
- Reinstein DZ, Archer TJ, Gobbe M. Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2012;28:195–201. doi:10.3928/1081597X-20120127-02 [CrossRef]
- Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness after hyperopic LASIK: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2010;26:555–564. doi:10.3928/1081597X-20091105-02 [CrossRef]
- Reinstein DZ, Archer TJ, Gobbe M. Epithelial thickness up to 26 years after radial keratotomy: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2011;27:618–624. doi:10.3928/1081597X-20110125-01 [CrossRef]
- Reinstein DZ, Gobbe M, Archer TJ, Couch D, Bloom B. Epithelial, stromal, and corneal pachymetry changes during orthokeratology. Optom Vis Sci. 2009;86:E1006–E1014. doi:10.1097/OPX.0b013e3181b18219 [CrossRef]
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- Reinstein DZ, Archer TJ, Gobbe M. Refractive and topographic errors in topography-guided ablation produced by epithelial compensation predicted by three-dimensional Artemis very high-frequency digital ultrasound stromal and epithelial thickness mapping. J Refract Surg. 2012;28:657–663. doi:10.3928/1081597X-20120815-02 [CrossRef]
- Reinstein DZ, Archer TJ, Gobbe M. Improved effectiveness of transepithelial phototherapeutic keratectomy versus topography-guided ablation degraded by epithelial compensation on irregular stromal surfaces. J Refract Surg. 2013;29:526–533.
- Chen X, Stojanovic A, Zhou W, Utheim TP, Stojanovic F, Wang Q. Transepithelial, topography-guided ablation in the treatment of visual disturbances in LASIK flap or interface complications. J Refract Surg. 2012;28:120–126. doi:10.3928/1081597X-20110926-01 [CrossRef]
- Chen X, Stojanovic A, Nitter TA. Topography-guided transepithelial surface ablation in treatment of recurrent epithelial ingrowths. J Refract Surg. 2010;26:529–532. doi:10.3928/1081597X-20100226-01 [CrossRef]
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Demographic and Refractive Data Before and After TE-PTKa
||TE-PTK + Refractive Ablation
||48 (32 to 75)
||44 (33 to 62)
|Preoperative SE (D)
||−0.41 ± 2.83 (−7.38 to +5.50)
||−1.57 ± 2.47 (−8.13 to +0.63)
|Postoperative SE (D)
||−0.58 ± 3.10 (−8.25 to +5.75)
||−0.99 ± 1.45 (−3.38 to +1.13)
|Intended SE (D)
||−0.80 ± 0.80 (−2.25 to 0.00)
|Accuracy to intended SE (D)
||−0.19 ± 1.03 (−2.38 to +1.88)
|Change SE (D)
||+0.18 ± 1.96 (−5.00 to +6.00)
||−0.58 ± 2.38 (−6.25 to +4.00)
|Preoperative cylinder (D)
||−2.84 ± 1.60 (0.00 to −8.00)
||−2.09 ± 1.57 (−0.50 to −5.00)
|Postoperative cylinder (D)
||−2.63 ± 1.40 (−0.50 to −5.00)
||−1.61 ± 1.06 (−0.25 to −3.25)
|Preoperative logMAR UDVA
||0.54 ± 0.36 (0.0 to 1.3)
||0.42 ± 0.40 (0.0 to 1.3)
|Postoperative logMAR UDVA
||0.55 ± 0.35 (0.0 to 1.3)
||0.35±0.30 (−0.1 to 0.8)
|Preoperative logMAR CDVA
||0.18 ± 0.14 (−0.1 to 0.5)
||0.09 ± 0.17 (−0.1 to 0.5)
|Postoperative logMAR CDVA
||0.09 ± 0.13 (−0.1 to 0.4)
||0.00 ± 0.10 (−0.2 to 0.2)