Journal of Refractive Surgery

Therapeutic Refractive Surgery Supplemental Data

Sequential Customized Therapeutic Keratectomy for Reis-Bücklers' Corneal Dystrophy: Long-term Follow-up

Paolo Vinciguerra, MD; Riccardo Vinciguerra, MD; J. Bradley Randleman, MD; Ingrid Torres, MD; Emanuela Morenghi, PhD; Fabrizio I. Camesasca, MD

Abstract

PURPOSE:

To report long-term outcomes of sequential customized therapeutic keratectomy for Reis–Bücklers' corneal dystrophy.

METHODS:

This was a retrospective review of 14 eyes of 8 patients with Reis–Bücklers' corneal dystrophy that underwent surgical peeling with a spatula of the epithelium and subepithelial membrane present in Reis–Bücklers' corneal dystrophy, with subsequent sequential customized therapeutic keratectomy featuring a multi-step approach with sequential, repeated customized excimer laser photoablations alternating with repeat intraoperative topographies to monitor and progressively reduce corneal irregularities.

RESULTS:

At the last follow-up of 5.09 ± 4.67 years (range: 0.29 to 12.87 years), mean corrected distance visual acuity improved from 20/50 (range: 20/630 to 20/30) to 20/25 (range: 20/20 to 20/40) (P < .01), whereas mean refraction changed from −0.29 ± 1.91 diopters (D) sphere and −0.75 ± 0.81 D cylinder preoperatively to 1.25 ± 2.10 D sphere and −1.08 ± 0.53 D cylinder postoperatively. Mean central keratometry values changed minimally from 42.67 ± 2.26 D preoperatively to 42.65 ± 2.30 D postoperatively. Coma significantly decreased from 0.60 ± 0.40 to 0.35 ± 0.28 μm (P < .05), whereas total higher order aberrations, spherical aberration, and trefoil remained stable. No patient underwent corneal transplantation. Disease recurrence required re-treatment using the same protocol in 14.28% of eyes (n = 2) for a mean of 5.86 ± 0.31 years (range: 5.64 to 6.08 years) after initial surgery.

CONCLUSIONS:

Five years after sequential customized therapeutic keratectomy, most eyes with Reis–Bücklers' corneal dystrophy showed improved visual acuity, stable refraction, and improved or stable higher order aberrations.

[J Refract Surg. 2018;34(10):682–688.]

Abstract

PURPOSE:

To report long-term outcomes of sequential customized therapeutic keratectomy for Reis–Bücklers' corneal dystrophy.

METHODS:

This was a retrospective review of 14 eyes of 8 patients with Reis–Bücklers' corneal dystrophy that underwent surgical peeling with a spatula of the epithelium and subepithelial membrane present in Reis–Bücklers' corneal dystrophy, with subsequent sequential customized therapeutic keratectomy featuring a multi-step approach with sequential, repeated customized excimer laser photoablations alternating with repeat intraoperative topographies to monitor and progressively reduce corneal irregularities.

RESULTS:

At the last follow-up of 5.09 ± 4.67 years (range: 0.29 to 12.87 years), mean corrected distance visual acuity improved from 20/50 (range: 20/630 to 20/30) to 20/25 (range: 20/20 to 20/40) (P < .01), whereas mean refraction changed from −0.29 ± 1.91 diopters (D) sphere and −0.75 ± 0.81 D cylinder preoperatively to 1.25 ± 2.10 D sphere and −1.08 ± 0.53 D cylinder postoperatively. Mean central keratometry values changed minimally from 42.67 ± 2.26 D preoperatively to 42.65 ± 2.30 D postoperatively. Coma significantly decreased from 0.60 ± 0.40 to 0.35 ± 0.28 μm (P < .05), whereas total higher order aberrations, spherical aberration, and trefoil remained stable. No patient underwent corneal transplantation. Disease recurrence required re-treatment using the same protocol in 14.28% of eyes (n = 2) for a mean of 5.86 ± 0.31 years (range: 5.64 to 6.08 years) after initial surgery.

CONCLUSIONS:

Five years after sequential customized therapeutic keratectomy, most eyes with Reis–Bücklers' corneal dystrophy showed improved visual acuity, stable refraction, and improved or stable higher order aberrations.

[J Refract Surg. 2018;34(10):682–688.]

Reis–Bücklers' corneal dystrophy, an anterior stromal dystrophy caused by mutations in the transforming growth factor beta–induced gene, typically presents in childhood with confluent, early, irregular geographic-like opacities varying in density and developing at the level of Bowman's layer and superficial stroma.1 Opacities are initially discrete, but subsequently extend to the limbus and deeper stroma. Corneal optical coherence tomography (OCT) shows a homogenous, confluent, membrane-like layer of hyperreflective deposits at the level of Bowman's layer and anterior stroma.2

Reis–Bücklers' corneal dystrophy progressively hinders visual acuity and causes recurrent erosions. Conservative therapy includes gels and ointments, but conventional treatment for extreme cases includes corneal transplantation.3 Femtosecond laser–assisted lamellar keratectomy, featuring a 110- to 140-μm corneal free cap, has been recently reported.4 Phototherapeutic keratectomy (PTK) using a 193-nm excimer laser has been used to treat vision-hampering corneal dystrophies causing recurring corneal erosion for the past 25 years.5–8 PTK appears to be the less invasive surgical solution, and it can be repeated, postponing for a long time partial- or full-thickness corneal transplantation (deep anterior lamellar keratoplasty or penetrating keratoplasty).9

We previously introduced custom PTK with intraoperative topography (called sequential customized therapeutic keratectomy [SCTK]), for the treatment of irregular corneas.10–12 This surgical technique features a multi-step procedure and intraoperative monitoring. Customized transepithelial excimer laser photoablation and smoothing are applied to remove irregularities and intraoperative topography is performed to verify attained corneal regularity.13 If topographic results are unsatisfactory, the cycle is repeated. Our clinical experience led us to believe that corneal surface regularity is more important than corneal transparency for maximal visual rehabilitation. When visual acuity is better, any residual spherocylindric defect is usually more tolerated, whereas the optical aberrations induced by irregularity may be less tolerated.

Given this hypothesis, we set out to determine the efficacy of SCTK for the management of Reis–Bücklers' corneal dystrophy. We report up to 7 years of follow-up of SCTK for the treatment of Reis–Bücklers' corneal dystrophy.

Patients and Methods

We retrospectively reviewed eyes of patients with a clinical diagnosis of Reis–Bücklers' corneal dystrophy, based on corneal appearance and medical history of visual-hampering opacities. Exclusion criteria were corneal thickness of less than 400 μm, concomitant ocular or systemic autoimmune disease, and history of dry eye, severe corneal infection, or keloids.

All patients provided their consent for use of their clinical data for scientific purposes. The Humanitas Clinical and Research Center Ethics Committee ruled that, on this basis and according to the Italian law, formal approval was not required for this monocentric retrospective study. This report of protocol awareness, conducted according to the ethical standards set in the 1964 Declaration of Helsinki, as revised in 2000, was deemed sufficient. In the preoperative and postoperative course, the following parameters were assessed: corrected visual acuity (CDVA), slit-lamp biomicroscopy, Goldmann tonometry, dilated funduscopy, corneal topography, and aberrometry for the evaluation of low and higher order aberrations (HOAs) (Costruzione Strumenti Oftalmici, Florence, Italy), and OPD II or III (Nidek, Gamagori, Japan) depending on the year of acquisition, tomography and pachymetry with Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany), and anterior segment OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA, or XR Avanti; Optovue Fremont, CA). Depending on the year, some data were not obtained because the particular instrument was not available (eg, anterior segment OCT with epithelial map).

SCTK for Reis–Bücklers' Corneal Dystrophy

The SCTK technique features a multi-step procedure and intraoperative monitoring.10–12 SCTK was performed with the Nidek EC-5000 excimer laser between 2001 and February 2013. All surgical procedures required more than one phase on the same day, as described below. Table A (available in the online version of this article) provides a full description of the procedure.

  1. Corneal epithelium was manually removed with a spatula and the underlying membrane replacing Bowman's layer was then delaminated with the spatula.

  2. Smoothing with masking fluid (wet PTK) aimed to smooth micro-irregularities.

  3. Intraoperative topography, tomography, and CDVA.

  4. Topography-guided custom ablation with a large optical zone aimed to further reduce the remaining HOAs.

  5. A second smoothing with masking fluid (wet PTK) aimed to smooth micro-irregularities.

  6. Intraoperative topography, tomography, and CDVA.

  7. Depending on the quality of the topography data and CDVA obtained in step 6, the procedure was deemed to be complete, or steps 4 to 6 were repeated (topography-guided ablation to further finalize the HOA treatment by regularizing the stromal surface).

Description of Sequential Customized Therapeutic Keratectomy

Table A:

Description of Sequential Customized Therapeutic Keratectomy

The target for stopping the procedure was defined as follows: (1) improvement of preoperative CDVA by at least two lines, regardless of the increase or decrease of refractive error; (2) all keratoscopic rings visible without the use of masking fluid; and (3) low curvature gradient (< 4.00 to 5.00 D/mm) in the central 6.5 mm evaluated, when available, with the corneal curvature gradient map implemented in the CSO devices (either the EyeTop Topographer or the Sirius) or with the evaluation of the tangential map. The curvature gradient is defined as the difference between the curvatures of two points and is calculated as the first derivative of the tangential curvature map in the radial direction.16

Whenever the target was not reached, this cycle was repeated, with a limit posed by the conventional stromal thickness safety limit of 250 μm. We previously demonstrated the stability of the patients treated with SCTK even with low residual stromal thickness.17 Mitomycin C was applied for 60 seconds and, after intensive corneal washout, a protective contact lens was placed and antibiotic and mydriatic eye drops were instilled.

Postoperatively, patients received antibiotic eye drops and were monitored daily until complete corneal reepithelialization. They underwent complete ophthalmologic examination, with corneal topography, tomography, and anterior segment OCT at 1, 3, 6, and 12 months postoperatively, then yearly. Cortisone eye drops were prescribed three times a day for the first 2 weeks and lubricants for up to 1 year.

Statistical Analysis

Data are expressed as mean ± standard deviation, median and range, or number and percentage, where appropriate. The comparison of variables was performed on paired data to evaluate the improvement or relapse of individual patients over time. To appraise the long-term safety and efficacy of SCTK, the preoperative values were compared with the last follow-up available for all patients. A move-forward follow-up strategy was used. Refractive outcome differences were assessed by dioptric power matrix evaluation using the approach suggested by Kaye.18 Data are expressed as mean ± standard deviation refraction (sphere, cylinder, and axis).

Differences between data were evaluated with the Wilcoxon signed-rank test. A P value of less than .05 was considered significant. Statistical analysis was performed using Stata 13 software (StataCorp, College Station, TX).

Results

Overall, 14 eyes of 8 male patients with Reis–Bücklers' corneal dystrophy underwent SCTK and were observed for 5.09 ± 4.67 years (range: 0.29 to 12.87 years). Eight were right eyes (57.1%) and 6 were left eyes (42.9%). Mean age was 42.88 ± 15.11 years (range: 21.75 to 62.92 years). Full data from all cases are presented in Table B (available in the online version of this article).

Features of Study Eyes

Table B:

Features of Study Eyes

Treatment was deemed sufficient in the first round (peeling plus smoothing) in 57.14% of eyes (n = 8), in two rounds in 21.42% of eyes (n = 3), and in three rounds in the remaining 2 eyes. The mean intraoperative pupillary keratometry value was 43.67. Table 1 presents changes in 5-mm corneal aberrations intraoperatively, presented at each phase of treatment, and at the end of follow-up. A move-forward follow-up strategy was used. None of the observed parameters showed a significant difference between preoperative and intraoperative (phases 1 and 2) values. At the end of follow-up, mean CDVA showed significant improvement from 0.44 to 0.12 logMAR (P = .023) (Figure 1). Ninety-two percent of the eyes gained one or more lines of CDVA, 8% had no change, and no eye lost lines. Figure 2 shows the safety profile of SCTK for Reis–Bücklers' corneal dystrophy in terms of the change in CDVA. Mean refraction was 0.09 −0.75 × 112.88 at baseline and +1.25 −1.08 × 110.73 at last follow-up available. There was no significant difference in spherical equivalent refraction before and after SCTK (P = .307). Figure 3 shows changes in spherical equivalent.

Description of Intraoperative and Final Corneal Surface Aberrations

Table 1:

Description of Intraoperative and Final Corneal Surface Aberrations

Box-and-whisker plot for logMAR corrected distance visual acuity (CDVA) for baseline versus last follow-up available.

Figure 1.

Box-and-whisker plot for logMAR corrected distance visual acuity (CDVA) for baseline versus last follow-up available.

Safety standard graph showing the change in lines of corrected distance visual acuity (CDVA) following sequential customized therapeutic keratectomy.

Figure 2.

Safety standard graph showing the change in lines of corrected distance visual acuity (CDVA) following sequential customized therapeutic keratectomy.

Refractive outcome graph showing the changes in spherical equivalent after sequential customized therapeutic keratectomy for Reis–Bücklers' corneal dystrophy. D = diopters

Figure 3.

Refractive outcome graph showing the changes in spherical equivalent after sequential customized therapeutic keratectomy for Reis–Bücklers' corneal dystrophy. D = diopters

Comparative evaluation of corneal HOAs between preoperative and final results showed a significant decrease in total root mean square (P = .004) and coma (P = .035) (Figures 45). Mean pupillary keratometry values changed minimally from 42.67 to 42.65 D (P = .647). Mean corneal thickness slightly decreased from 554.62 to 510.40 μm (P = .059). Two patients were lost to follow-up.

Box-and-whisker plot for total root-mean-square (RMS) aberrations showing a significant decrease at baseline versus last follow-up available.

Figure 4.

Box-and-whisker plot for total root-mean-square (RMS) aberrations showing a significant decrease at baseline versus last follow-up available.

Box-and-whisker plot for coma showing a significant decrease at baseline versus last follow-up available.

Figure 5.

Box-and-whisker plot for coma showing a significant decrease at baseline versus last follow-up available.

Disease recurrence required re-treatment in both eyes (14.3%) of the same patient, at 5.64 years in the left eye and 6.08 years in the right eye. In both cases, a progressive decrease in visual acuity and recurrence of corneal erosions was observed. Given the limited invasiveness of SCTK, we decided to repeat surgery. Nine years after the second SCTK, CDVA in both eyes was better than preoperatively. No patient required corneal transplantation.

We describe in detail three cases to provide the full spectrum of the treatment process and outcomes.

Case 2

A 55-year-old man with bilateral Reis–Bücklers' corneal dystrophy underwent treatment in his right eye after 2 years of progressive decrease in visual acuity. Initial visual acuity was 0.7 logMAR with manifest refraction of −2.50 sphere. Three months postoperatively, his visual acuity in the right eye was 0.05 logMAR with manifest refraction of −1.50 sphere. Figure A (available in the online version of this article) shows the initial, intraoperative, and final corneal topography.

Case 2. (A–B) Preoperative topography, instantaneous algorithm, and keratoscopy. (C–D) Intraoperative topography and keratoscopy after one phase of sequential customized therapeutic keratectomy. (E–F) Postoperative topography, instantaneous algorithm, and keratoscopy. Note the improved regularity of keratoscopic rings (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Figure A.

Case 2. (A–B) Preoperative topography, instantaneous algorithm, and keratoscopy. (C–D) Intraoperative topography and keratoscopy after one phase of sequential customized therapeutic keratectomy. (E–F) Postoperative topography, instantaneous algorithm, and keratoscopy. Note the improved regularity of keratoscopic rings (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Case 7

A 22-year-old man reporting bilateral Reis–Bücklers' corneal dystrophy since infancy with a history of recurring and bilateral corneal erosions underwent treatment in his right eye. Initial visual acuity, not ameliorable with correction, was 0.52 logMAR. Twenty-two months postoperatively, his visual acuity in the right eye was 0.00 logMAR and no further episode of corneal erosion was reported. Figure B (available in the online version of this article) shows the initial, intraoperative, and final corneal topography.

Case 7. (A–B) Preoperative topography, instantaneous algorithm, and keratoscopy. (C–D) Intraoperative topography and keratoscopy after one phase of sequential customized therapeutic keratectomy. (E–F) Postoperative topography, instantaneous algorithm, and keratoscopy. Now topography is complete, with only small bow-tie residual astigmatism (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Figure B.

Case 7. (A–B) Preoperative topography, instantaneous algorithm, and keratoscopy. (C–D) Intraoperative topography and keratoscopy after one phase of sequential customized therapeutic keratectomy. (E–F) Postoperative topography, instantaneous algorithm, and keratoscopy. Now topography is complete, with only small bow-tie residual astigmatism (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Case 4

A 50-year-old man reported progressive bilateral visual acuity decrease since 1992, with a diagnosis of Reis–Bücklers' corneal dystrophy and visual acuity of 0.60 logMAR not ameliorable with correction. He underwent SCTK in his left eye. Almost 6 years after surgery, his visual acuity was 0.30 logMAR with a manifest refraction of +3.00 −1.25 × 140 and he underwent re-treatment in his left eye. At last follow-up examination, 6.5 months after re-treatment, visual acuity in the left eye was 0.22 logMAR with a manifest refraction of −6.00 −2.00 × 155. Figures CD (available in the online version of this article) present corneal topographies from 2003 to 2009.

Case 4. All topographies are in instantaneous algorithm. (A–B) Preoperative topography and keratoscopy. (C–D) Intraoperative phase 1 topography and keratoscopy. (E–F) Topography and keratoscopy almost 6 years postoperatively and immediately before re-treatment due to recurrence of Reis–Bücklers' corneal dystrophy (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Figure C.

Case 4. All topographies are in instantaneous algorithm. (A–B) Preoperative topography and keratoscopy. (C–D) Intraoperative phase 1 topography and keratoscopy. (E–F) Topography and keratoscopy almost 6 years postoperatively and immediately before re-treatment due to recurrence of Reis–Bücklers' corneal dystrophy (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Case 4. Re-treatment for recurrence of Reis–Bücklers' corneal dystrophy of case 3, topographies in instantaneous algorithm and keratoscopies: (A–B) phase 1, (C–D) phase 2, (D–E) phase 3, and (F–G) 6.5 months after re-treatment (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Figure D.

Case 4. Re-treatment for recurrence of Reis–Bücklers' corneal dystrophy of case 3, topographies in instantaneous algorithm and keratoscopies: (A–B) phase 1, (C–D) phase 2, (D–E) phase 3, and (F–G) 6.5 months after re-treatment (CSO topographer; Costruzione Strumenti Oftalmici, Florence, Italy).

Discussion

The primary goals of PTK are to improve visual function and prevent painful recurrent corneal erosions.19 In the past 16 years, we have treated Reis–Bücklers' corneal dystrophy using the SCTK technique. Our results demonstrate the potential benefits of this approach; 90.90% of treated eyes had improved spectacle-corrected acuity, with 72.72% achieving two or more lines of improvement. Only 2 eyes (14.3%) of the same patient showed recurrence requiring a retreatment, almost 6 years after initial laser treatment, with improved CDVA after repeat SCTK treatment.

Surgical treatment options for Reis–Bücklers' corneal dystrophy include penetrating or lamellar keratoplasty, blunt dissection of the subepithelial fibrous tissue layer (superficial keratectomy), and PTK.9,20,21 Superficial keratectomy provides a safe, simple, and effective means to obtain temporary symptomatic relief and improvement of vision in cases of Reis–Bücklers' corneal dystrophy that are refractory to more conservative management.21 Lamellar and penetrating keratoplasty solve the dystrophy problems, but are invasive, subject to rejection, graft failure, infection, and irregular astigmatism, require a long rehabilitation, and do not exclude recurrence.4,9

Since the early 1990s, Fagerholm6 reported on the use of excimer laser photoablation (PTK) for the treatment of anterior stromal dystrophies. Compared to any type of keratoplasty, excimer laser PTK is the least aggressive procedure and probably the safest, obviating or delaying the need for penetrating keratoplasty.10,19 Eyes with Reis–Bücklers' corneal dystrophy treated with PTK always improved their vision substantially, but reported cases are usually aggregated with other types of anterior stromal dystrophies and are small in number.5–7,22–24 In 2014, Fogla and Knyazer9 reported a series of 4 eyes with Reis–Bücklers' corneal dystrophy successfully treated with microkeratome-assisted superficial anterior lamellar keratoplasty, with mean CDVA of 0.2 logMAR at 19 months. In 2016, Steger et al.4 described a case series of 8 eyes of 6 patients with anterior corneal dystrophies, including 4 with Reis–Bücklers' corneal dystrophy, who underwent lamellar keratectomy using the femtosecond laser. In these cases, CDVA at 2 years improved significantly, and patients with Reis–Bücklers' corneal dystrophy showed the best visual outcome at 2 years. Table C (available in the online version of this article) compares treatment of eyes with Reis–Bücklers' corneal dystrophy.9,17,24,25

Comparison of Literature on the Treatment of Reis–Bücklers' Corneal Dystrophy

Table C:

Comparison of Literature on the Treatment of Reis–Bücklers' Corneal Dystrophy

The intended goal of PTK treatment is important and must be shared preoperatively with patients. In our opinion, corneal surface regularity is more important to visual rehabilitation than corneal transparency. Optical aberrations induced by corneal surface irregularity decrease vision in a way not correctable with spectacles. Eliminating them improves vision and makes any possible residual refractive defect more tolerable.26 With this target in mind, we treated these eyes with SCTK pursuing corneal regularity and aberrations more than final refractive defect. Stability of the eyes treated with SCTK even with low residual stromal thickness has been demonstrated in the past.17

Preoperative anterior segment OCT provided essential information pertaining to the presence, depth, and thickness of the subepithelial membrane (Figure E, available in the online version of this article). Surgery consisted of an initial, careful, mechanical removal of the epithelium and the characteristic Reis–Bücklers' corneal dystrophy subepithelial membrane with a spatula. Once the normal stroma was exposed, regularization through excimer laser ablation was pursued. Key to this approach was intraoperative topography, a powerful and accurate method to assess the preoperative and intraoperative corneal irregularities and elaborate, when necessary in sequential, repeated steps, a topography-guided ablation aimed at regularizing corneal surface.10–12

(A–B) Preoperative and (C–D) postoperative anterior segment optical coherence tomography and epithelial maps. Presence, depth, and thickness of the subepithelial membrane is easily detected and measured. Note stromal opacity extending down to 352 μm.

Figure E.

(A–B) Preoperative and (C–D) postoperative anterior segment optical coherence tomography and epithelial maps. Presence, depth, and thickness of the subepithelial membrane is easily detected and measured. Note stromal opacity extending down to 352 μm.

A key tool in our surgical treatment of Reis–Bücklers' corneal dystrophy was smoothing with masking fluid. Since 1998, we have demonstrated that phototherapeutic-like smoothing improved corneal stromal surface regularity immediately after PRK and provided better refractive and optical outcomes.27–29 Excimer laser smoothing with masking fluid has always been an integral part of SCTK, aimed at refining and improving final corneal surface regularity.27 There are encouraging reports on the use of transepithelial PTK to regularize highly aberrated corneas by using the epithelium as a natural masking agent, although to our knowledge not for Reis–Bücklers' corneal dystrophy.26 In this dystrophy, the thick subepithelial membrane was removed with a spatula, and the masking fluid was thereafter necessary to apply the therapeutic photoablation and regularize the highly irregular corneal surface.

Since October 2014, we have been treating Reis–Bücklers' corneal dystrophy with a different, more advanced type of laser. We did not consider the five eyes treated since then on purpose, to avoid possible confusion in results.

Recurrence in 13 eyes with Reis–Bücklers' corneal dystrophy mostly occurred at an average of 21.6 months after PTK in 47%.19 Recurrence of deposits in the graft occurs approximately 6 years after corneal transplantation.1 In our series, only 2 eyes (13.3%) showed recurrence requiring a re-treatment almost 6 years after initial laser treatment. Topical 0.02% mitomycin C has been suggested to reduce the recurrence of Reis–Bücklers' corneal dystrophy.23 We routinely used mitomycin C in all of our cases, and our findings agree with these results.

We did not observe induction of any significant hyperopic shift, irregular astigmatism, or scarring, which have been cited as complications of PTK. Several factors may be considered to explain this. A 10-mm ablation zone size implies similar tissue removal over a wide corneal portion, whereas smaller diameter ablation induces central flattening. Thus, the chances of corneal keratometry changes are reduced. Use of masking fluid exposes the emerging stromal irregular peaks, and intraoperative monitoring of results makes correcting a large amount of HOAs possible. Biomechanically, a wide ablation with selective removal of major irregularities prevents concentration of biomechanical weakening only in the central corneal portion.9

There are limitations to the results of this study. First, there is no comparative group; it would have been better to have a standard PTK group to compare against the STCK technique. Second, the follow-up is highly variable, and due to the retrospective nature of the study there is data loss for some eyes at certain time points. Finally, due to the rarity of the condition, this nevertheless is a small study group with its inherent limitations.

To our knowledge, this is the largest series of long-term results in the treatment of Reis–Bücklers' corneal dystrophy, and includes the longest follow-up. SCTK provided long-term improvement of visual acuity, stable, refraction, and freedom from recurring erosions. No eye had to undergo corneal transplantation and only 2 eyes required re-treatment.

References

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  23. Miller A, Solomon R, Bloom A, Palmer C, Perry HD, Donnenfeld ED. Prevention of recurrent Reis-Bücklers' dystrophy following excimer laser phototherapeutic keratectomy with topical mitomycin C. Cornea. 2004;23:732–735. doi:10.1097/01.ico.0000127476.37175.6d [CrossRef]
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  25. Lawless MA, Cohen P, Rogers C. Phototherapeutic keratectomy for Reis-Bücklers' dystrophy. Refract Corneal Surg. 1993;9:S96–S98.
  26. Reinstein DZ, Archer TJ, Dickeson ZI, Gobbe M. Transepithelial phototherapeutic keratectomy protocol for treating irregular astigmatism based on population epithelial thickness measurements by artemis very high-frequency digital ultrasound. J Refract Surg. 2014;30:380–387. doi:10.3928/1081597X-20140508-01 [CrossRef]
  27. Vinciguerra P, Camesasca FI, Vinciguerra R, et al. Advanced surface ablation with a new software for the reduction of ablation irregularities. J Refract Surg. 2017;33:89–95. doi:10.3928/1081597X-20161122-01 [CrossRef]
  28. Vinciguerra P, Camesasca FI, Torres IM. Transition zone design and smoothing in custom laser-assisted subepithelial keratectomy. J Cataract Refract Surg. 2005;31:39–47. doi:10.1016/j.jcrs.2004.10.041 [CrossRef]
  29. Vinciguerra P, Albè E, Camesasca FI, Trazza S, Epstein D. Wavefront- versus topography-guided customized ablations with the NIDEK EC-5000 CX II in surface ablation treatment: refractive and aberrometric outcomes. J Refract Surg. 2007;23(9 suppl):S1029–S1036.

Description of Intraoperative and Final Corneal Surface Aberrations

Aberrations (μm) (5-mm Pupil)Preop (n = 14)Intraoperative (Round 1) (n = 13)P (Preop vs Round 1)Intraoperative (Round 2) (n = 5)P (Preop vs Round 2)Intraoperative (Round 3) (n = 2)Final (n = 14)P (Preop vs Final)
Total RMS5.30 ± 7.552.47 ± 1.89.5832.30 ± 0.83.1441.94 ± 0.701.71 ± 1.65.004
SA0.18 ± 0.340.09 ± 0.09.3820.05 ± 0.16.500−0.21 ± 0.330.16 ± 0.1.730
Coma0.60 ± 0.400.40 ± 0.28.1520.55 ± 0.30.5000.21 ± 0.090.35 ± 0.28.035
Trefoil0.65 ± 0.590.44 ± 0.35.5530.49 ± 0.34.5000.56 ± 0.040.41 ± 0.45.346
Astigmatism1.36 ± 0.900.97 ± 0.72.1580.83 ± 0.42.7150.36 ± 0.060.85 ± 0.85.328
HOAs1.10 ± 0.660.69 ± 0.53.0710.75 ± 0.47.5810.90 ± 0.060.67 ± 0.61.084

Description of Sequential Customized Therapeutic Keratectomy

Phase 1: Corneal Epithelium and Underlying Membrane RemovalCorneal epithelium is manually removed with a spatula to better identify and then delaminate with the spatula the underlying membrane replacing Bowman's layer. Phase 2: Smoothing with Masking Fluid (Wet PTK)The stromal surface is initially regularized by smoothing to remove corneal micro-irregularities and achieve a regular stromal bed as similar as possible to the physiological Bowman's layer. Smoothing is performed as follows:

A drop of hyaluronic acid masking fluid (0.25% of hyaluronic acid, 280 to 320 mOsm/L osmolarity, neutral pH = 7.2 to 7.4) (Laservis; Chemedica, Munich, Germany) is applied to the cornea.

A planar PTK ablation is applied with a diameter of 10 mm and 20 µm depth, thus covering the entire corneal diameter and minimizing any potential hyperopic shift.

The masking fluid is continuously distributed over the corneal surface during ablation using a spatula (eg, Buratto's spatula; ASICO, Westmont, IL).10–12

The masking fluid is added and evenly distributed with the spatula to maintain a thin layer of fluid and avoid the formation of dry areas.

This masking fluid features the same ablation rate as the stromal tissue. For this reason, most of the ablation is done on the fluid and a minimal amount of the small irregularities of the stroma (“peaks” emerging from the fluid layer). As previously described, the actual ablation is only a few microns because of this protective action of the masking fluid.10,11,14,15 Irregular peaks will appear and be ablated. Overheating with the Nidek scanning slit was avoided adopting a 10-Hz ablation. SCTK and smoothing diameter were always 10 mm in diameter, thus involving the entire corneal diameter to minimize hyperopic shift. Phase 3: Intraoperative Topography, Tomography, and CDVAAfter this treatment, the patient was taken to a nearby examining room and intraoperative topography, tomography, and CDVA were obtained to monitor the surgical efficacy. All intraoperative corneal measurements were acquired with the Sirius or EyeTop Topographer (Costruzione Strumenti Oftalmici, Florence, Italy), depending on the year of surgery. To obtain a reliable measurement, keratoscopy was performed after irrigation with balanced salt solution and one drop of masking fluid. The patient was asked to blink, and, if no dry areas were detected after 5 to 10 seconds, the image was acquired. Sitting position entailed regular distribution of masking fluid. We previously published that intraoperative, epithelium-free topography-based corneal aberrometry is a feasible option for custom ablation in highly aberrated eyes.12 Even if corneal edema might occur, because it is diffused, it is not expected to change the overall shape of the cornea, but only its thickness. Phase 4: Topography-Guided Custom Ablation With a Large Optical ZoneIf deposit-related corneal opacities appeared to be visually significant, and considering corneal pachymetry as estimated with Scheimpflug imaging, intraoperative topography-guided custom ablation with the largest possible optical zone available (eg, 8.5-mm optical zone with transition zone up to 10 mm) was then planned and performed. The least possible ablation depth providing corneal regularization was chosen. The goal was eliminating the remaining higher order aberrations. Correction of astigmatism, when present, was a secondary goal. Phases 5 to 7: Wet PTK, Intraoperative Evaluation, and Decision Whether to Stop or ContinueAs after the first ablation, another wet PTK smoothing ablation was performed. The patient was then taken back to a nearby examining room to again assess the CDVA and obtain an intraoperative topography measurement to define the progress of the procedure. As before, a drop of masking fluid was applied prior to acquiring the topography scan and assessment of visual acuity. This cycle of custom ablation with PTK smoothing, intraoperative topography/tomography, and visual acuity measurement (round 2 and following) was repeated until the surgeon deemed that the preoperative target was reached.

Features of Study Eyes

PatientAge (y)EyeDate of SurgeryPreoperativeIntraoperativePostoperative



CDVA (logMAR)Sph (D)Cyl (D)AxisSE (D)Pachy (µm)Mean Pupillary K (D) PhasesNo. of PupillaryaMean K (D)F/U (mo)CDVA (logMAR)Sph (D)Cyl (D)AxisSE (D)Pachy (µm)Mean Pupillary K (D)
125.91OS05/28/20010.020.000.000.0054742.711.0043.25154.470.050.00−1.0060.00−0.5051642.50
254.78OD07/11/20020.70−2.500.00−2.5058947.471.0045.503.470.00−1.500.00−1.5047.62
327.29OD10/14/20020.10−0.500.00−0.5053143.152.0043.88137.670.050.00−0.50150.00−0.2552342.90
4b50.64OS02/17/20030.602.50−2.001801.5052841.181.0039.2568.600.303.00−1.25143.002.3857143.98
5b50.73OD03/24/20030.520.000.000.0053043.002.0043.8867.430.305.50−1.0060.005.0057242.18
662.92OD11/19/20040.12−3.50−0.5020−3.7557543.211.0042.75
730.49OD02/20/20060.520.00−1.0015−0.5061842.291.0042.626.630.020.00−1.50170.00−0.7555643.00
856.28OS10/06/20080.303.00−1.251432.37557143.973.0048.58116.530.104.00−1.0090.003.5040440.88
956.81OD04/20/20090.704.00−2.00703.0055541.123.0045.08110.000.520.00−2.0020.00−1.0041138.19
1021.75OD04/05/20090.520.000.000.0052042.842.0045.1522.500.000.25−1.75180.00−0.6342843.75
1140.92OD10/12/20090.40−3.250.00−3.2551738.641.0041.25
1222.53OS02/15/20100.520.00−0.75180−0.37556945.321.0012.930.050.00−1.00170.00−0.50563
1361.68OS07/02/20100.600.50−1.001150.002.0042.883.430.003.00−1.0075.002.5042.75
1437.52OS02/27/20130.521.00−2.001800.0056039.8528.630.000.75−1.00100.000.2550041.43
Mean42.880.440.09−0.75112.88−0.29554.6242.671.6243.6761.030.121.25−1.08110.730.71510.4042.65
SD15.110.222.180.8170.181.9129.812.260.772.3356.100.172.100.5354.412.0959.102.30
Min21.750.02−3.50−2.0015.00−3.75517.0038.641.0039.253.430.00−1.50−2.0020.00−1.50411.0038.19
Max62.920.704.000.00180.003.00618.0047.473.0048.58154.470.525.500.00180.005.00572.0047.62

Comparison of Literature on the Treatment of Reis–Bücklers' Corneal Dystrophy

AuthorYearTechniqueNo. of EyesPreop CDVA (Feet, Mean ± SD)F/U (mo)Postop CDVA (Feet, Mean ± SD)
Lawless et al.251993PTK920/270 ± 20/206620/33 ± 20/8
Stewart et al.222002PTK420/88 ± 20/4322.320/54 ± 20/48
Fogla & Knyazer 92014SALK420/135 ± 20/7519.00 ± 3.5620/33 ± 20/10
Steger et al.42016FLK420/195 ± 20/1432920/20 ± 20/5
Vinciguerra et al.122018SCTK1420/50 ± 20/3243.44 ± 53.1820/25 ± 20/20
Authors

From the Eye Center, Humanitas Clinical and Research Center, Milan, Italy (PV, IT, FIC); St. Paul's Eye Unit, Royal Liverpool and Broadgreen University Hospital, Liverpool, United Kingdom (RV); USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California (JBR); and the Biostatistic Unit, Humanitas Research Hospital, Milan, Italy (EM).

Drs. Paolo and Riccardo Vinciguerra are consultants for Oculus Optikgeräte GmbH. The remaining authors have no financial or proprietary interest in the materials presented herein.

Drs. Paolo Vinciguerra and Camesasca contributed equally to this work and should be considered as equal first authors.

Dr. Randleman did not participate in the editorial review of this manuscript.

Supported in part by an unrestricted departmental grant to the USC Roski Eye Institute Department of Ophthalmology from Research to Prevent Blindness, Inc.

AUTHOR CONTRIBUTIONS

Study concept and design (PV, FIC); data collection (IT, FIC); analysis and interpretation of data (PV, RV, JBR, EM, FIC); writing the manuscript (PV, JBR, EM, FIC); critical revision of the manuscript (PV, RV, JBR, IT, FIC); statistical expertise (EM); supervision (PV)

Correspondence: Fabrizio I. Camesasca, MD, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy. E-mail: fabrizio.camesasca@humanitas.it

Received: May 10, 2018
Accepted: August 28, 2018

10.3928/1081597X-20180829-01

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