Michael A. Grentzelos

Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas

PURPOSE To report the outcomes after corneal collagen cross-linking (CXL) treatment with riboflavin and ultraviolet-A (UVA) irradiation in patients with thin corneas (minimum corneal thickness less than 400 μm after epithelial removal and before riboflavin instillation). DESIGN Prospective case series. METHODS Twelve patients (14 eyes, with minimum corneal thickness less than 400 μm after epithelial removal) were included in the study. All patients underwent riboflavin-UVA-induced CXL using the standard CXL (Dresden) protocol. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) (decimal scale), manifest refraction (diopters, D), and topography were evaluated at baseline and at 1, 3, 6, and 12 months follow-up. Images of the endothelium were acquired with a modified confocal scanning laser ophthalmoscope. RESULTS No intraoperative or postoperative complications were observed in this patient series. Mean minimum preoperative corneal thickness at the apex of the cone after epithelial removal and before riboflavin instillation was 373.92 ± 22.92 μm (range 340-399 μm). UDVA and CDVA improved from 0.25 ± 0.15 and 0.40 ± 0.20 to 0.27 ± 0.17 and 0.49 ± 0.20 respectively at the last follow-up examination. There was a reduction of the mean keratometry readings from 51.99 ± 5.57 D to 49.33 ± 4.82 D at the last follow-up. A significant decrease of endothelial cell density was observed (preoperative: 2733 ± 180 cells/mm(2) [range 2467-3016], last follow-up visit: 2441 ± 400 cells/mm(2) [range 1448-2920], P < .01). CONCLUSIONS CXL in thin corneas with minimum corneal thickness less than 400 μm after epithelial removal seems to result in a significant endothelial cell density decrease postoperatively. This finding was not related to other intraoperative or postoperative complications.

Intraoperative Pachymetric Measurements during Corneal Collagen Cross-Linking with Riboflavin and Ultraviolet A Irradiation

OBJECTIVE To study central corneal pachymetric variations during corneal collagen cross-linking (CXL) treatment with the use of riboflavin and ultraviolet A irradiation (UVA). DESIGN Prospective, noncomparative, interventional clinical study. PARTICIPANTS Fifteen keratoconic patients (19 eyes) were enrolled. METHODS All patients underwent riboflavin-UVA-induced corneal CXL. Intraoperative central corneal thickness (CCT) measurements using ultrasound pachymetry were performed during the procedure. Measurements were obtained after epithelial removal, after riboflavin drop instillation, and every 5 minutes (6 interval times) during UVA irradiation (30 minutes). MAIN OUTCOME MEASURES Central corneal thickness measurements. RESULTS Mean patient age was 26.9+/-6.5 years (range, 17-40 years). Ten were male and 5 were female. Mean preoperative CCT was 458.5+/-21.5 microm (range, 427-494 microm; 95% confidence interval [CI], 448-467 microm) and 415.7+/-20.6 microm (range, 400-468 microm; 95% CI, 406-426 microm) before and after epithelial removal, respectively. There was a statistically significant decrease (mean, 75 microm) of CCT between the epithelial removal interval (415.7+/-20.6 microm; range, 400-468 microm) and at the end of riboflavin solution instillation (340.7+/-22.9 microm; range, 292-386 microm; P<0.001). There was no statistically significant change in CCT during irradiation (P>0.05). There was no statistically significant difference between preoperative and 1-month postoperative endothelial cell count (preoperative, 2780+/-197 to 1-month postoperative, 2713+/-116; P = 0.14). No intraoperative, early postoperative, or late postoperative complications were observed in this patient series. CONCLUSIONS During corneal CXL with the use of riboflavin and UVA irradiation, a statistically significant decrease of CCT was demonstrated.

Simultaneous Topography-Guided Photorefractive Keratectomy Followed by Corneal Collagen Cross-linking for Keratoconus

PURPOSE To present the long-term results after simultaneous photorefractive keratectomy followed by corneal collagen cross-linking for keratoconus. DESIGN Prospective, interventional, consecutive case series. METHODS In this study, 26 patients (31 eyes) with progressive keratoconus were included. All patients underwent customized topography-guided photorefractive keratectomy immediately followed by corneal collagen cross-linking with the use of riboflavin and ultraviolet A irradiation. Epithelium was removed by transepithelial phototherapeutic keratectomy in all cases. RESULTS Mean follow-up was 19.53 ± 3.97 months (range, 12 to 25 months). Mean preoperative spherical equivalent was -2.3 ± 2.8 diopters (D), whereas at the last follow-up examination, it was significantly (P < .001) reduced to -1.08 ± 2.41 D. Logarithm of the minimal angle of resolution uncorrected and best-corrected visual acuity were reduced significantly by 0.46 and 0.084 (P < .001), respectively, at the last follow-up examination. Finally, mean steep and flat keratometry readings were reduced by 2.35 (P < .001) and 1.18 (P = .013) at the last follow-up examination. CONCLUSIONS Simultaneous photorefractive keratectomy followed by corneal collagen cross-linking seems to be a promising treatment alternative in our series of keratoconic patients.

Combined transepithelial phototherapeutic keratectomy and corneal collagen cross-linking for progressive keratoconus.

PURPOSE To compare the outcomes of corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus using 2 different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) versus mechanical epithelial debridement. DESIGN Prospective, comparative, interventional case series. PARTICIPANTS Thirty-four patients (38 eyes) with progressive keratoconus were enrolled. METHODS All patients underwent uneventful CXL treatment. Sixteen patients (19 eyes) underwent epithelial removal using t-PTK (group 1) and 18 patients (19 eyes) underwent mechanical epithelial debridement using a rotating brush (group 2) during CXL treatment. Visual and refractive outcomes were evaluated along with corneal confocal microscopy findings preoperatively and at 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, and keratometry readings. RESULTS No intraoperative or postoperative complications were observed in any of the patients. In group 1, logarithm of the minimum angle of resolution mean UDVA and mean CDVA improved from 0.99 ± 0.71 and 0.30 ± 0.26 preoperatively to 0.63 ± 0.42 (P = 0.02) and 0.19 ± 0.18 (P = 0.008) at 12 months postoperatively, respectively. In group 2, neither mean UDVA nor mean CDVA demonstrated a significant improvement at 12 months postoperatively (P>0.05). In group 1, mean corneal astigmatism improved from -5.84 ± 3.80 diopters (D) preoperatively to -4.31 ± 2.90 D (P = 0.015) at the last follow-up, whereas in group 2 there was no significant difference at the same postoperative interval (P>0.05). No endothelial cell density alterations were observed throughout the follow-up period for both groups (P>0.05). CONCLUSIONS Epithelial removal using t-PTK during CXL results in better visual and refractive outcomes in comparison with mechanical epithelial debridement.

Corneal stroma demarcation line after standard and high-intensity collagen crosslinking determined with anterior segment optical coherence tomography

Purpose To use anterior segment optical coherence tomography (AS‐OCT) to compare corneal stroma demarcation line depth after corneal collagen crosslinking (CXL) with 2 treatment protocols. Setting Vardinoyiannion Eye Institute of Crete, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. Design Prospective comparative interventional case series. Methods Corneal collagen crosslinking was performed in all eyes using the same ultraviolet‐A (UVA) irradiation device (CCL‐365). Eyes were treated for 30 minutes with 3 mW/cm2 according to the standard Dresden protocol (Group 1) or for 10 minutes with 9 mW/cm2 of UVA irradiation intensity (Group 2). One month postoperatively, 2 independent observers measured the corneal stroma demarcation line using AS‐OCT. Results Sixteen patients (21 eyes) were enrolled. Group 1 comprised 7 patients (9 eyes) and Group 2, 9 patients (12 eyes). The mean corneal stroma demarcation line depth was 350.78 &mgr;m ± 49.34 (SD) (range 256.5 to 410 &mgr;m) in Group 1 and 288.46 ± 42.37 &mgr;m (range 238.5 to 353.5 &mgr;m) in Group 2; the corneal stroma demarcation line was statistically significantly deeper in Group 1 than in Group 2 (P=.0058, t test for unpaired data). Conclusion The corneal stroma demarcation line was significantly deeper after a 30‐minute CXL treatment than after a 10‐minute CXL procedure with high‐intensity UVA irradiation. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Correlation of the Corneal Collagen Cross-Linking Demarcation Line Using Confocal Microscopy and Anterior Segment Optical Coherence Tomography in Keratoconic Patients

PURPOSE To evaluate and compare the depth of the corneal stromal demarcation line after corneal collagen cross-linking (CXL) using 2 different methods: confocal microscopy and anterior segment optical coherence tomography (AS OCT). DESIGN Prospective, comparative, interventional case series. METHODS Seventeen patients (18 eyes) with progressive keratoconus were enrolled. All patients underwent uneventful CXL treatment according to the Dresden protocol. One month after surgery, corneal stromal demarcation line depth was measured in all patients by 2 independent observers using confocal microscopy and AS OCT. RESULTS Mean corneal stromal demarcation line depth measured using confocal microscopy by the first observer was 306.22 ± 51.54 μm (range, 245 to 417 μm) and that measured by the second observer was 303.5 ± 46.98 μm (range, 240 to 390 μm). The same measurements using AS OCT were 300.67 ± 41.56 μm (range, 240 to 385 μm) and 295.72 ± 41.01 μm (range, 228 to 380 μm) for the first and second observer, respectively. Pairwise comparisons did not reveal any statistically significant difference between confocal microscopy and AS OCT measurements for both observers (P = .3219 for the first observer and P = .1731 for the second observer). CONCLUSIONS Both confocal microscopy and AS OCT have similar results in evaluating the depth of the corneal stromal demarcation line after CXL.

Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol.

PURPOSE To compare the corneal stromal demarcation line depth using anterior segment optical coherence tomography (AS-OCT) after corneal collagen cross-linking (CXL) using 2 different treatment protocols: the standard Dresden protocol (30 minutes with 3 mW/cm(2)) and a modified-accelerated protocol (14 minutes with 9 mW/cm(2)). DESIGN Prospective, comparative study. METHODS Forty-three keratoconic patients (52 eyes) were enrolled. All patients underwent CXL using the same high-intensity ultraviolet-A (UV-A) irradiation device. Twenty-six eyes were treated for 30 minutes with 3 mW/cm(2) according to the standard Dresden protocol (Group 1), while 26 eyes were treated with a novel modified-accelerated CXL protocol for 14 minutes with 9 mW/cm(2) of UV-A irradiation intensity (Group 2). One month postoperatively, corneal stromal demarcation line depth was measured by 2 independent observers using AS-OCT. RESULTS Corneal stromal demarcation line depth was assessed with no significant difference between observer measurements for both groups (P = .676 for Group 1 and P = .566 for Group 2). Mean corneal stromal demarcation line depth was 337.00 ± 46.46 μm for Group 1 and 322.91 ± 48.28 μm for Group 2. There was no statistically significant difference (P = .243) in the corneal stromal demarcation line depth between the 2 groups. CONCLUSIONS Corneal stromal demarcation line depth using UV-A with 3 mW/cm(2) for 30 minutes and 9 mW/cm(2) for 14 minutes was similar. A modified-accelerated protocol of 14 minutes of CXL provided the same treatment depth as the classic Dresden protocol.

Topography-guided Transepithelial PRK After Intracorneal Ring Segments Implantation and Corneal Collagen CXL in a Three-Step Procedure for Keratoconus

PURPOSE To present the results of topography-guided transepithelial photorefractive keratectomy (PRK) after intracorneal ring segments implantation followed by corneal collagen cross-linking (CXL) for keratoconus. METHODS In this prospective case series, 10 patients (16 eyes) with progressive keratoconus were included. All patients underwent topography-guided transepithelial PRK after Keraring intracorneal ring segments (Mediphacos Ltda) implantation, followed by CXL treatment. The follow-up period was 6 months after the last procedure for all patients. Time interval between both intracorneal ring segments implantation and CXL and between CXL and topography-guided transepithelial PRK was 6 months. RESULTS LogMAR mean uncorrected distance visual acuity and mean corrected distance visual acuity were significantly improved (P<.05) from 1.14±0.36 and 0.75±0.24 preoperatively to 0.25±0.13 and 0.13±0.06 after the completion of the three-step procedure, respectively. Mean spherical equivalent refraction was significantly reduced (P<.05) from -5.66±5.63 diopters (D) preoperatively to -0.98±2.21 D after the three-step procedure. Mean steep and flat keratometry values were significantly reduced (P<.05) from 54.65±5.80 D and 47.80±3.97 D preoperatively to 45.99±3.12 D and 44.69±3.19 D after the three-step procedure, respectively. CONCLUSIONS Combined topography-guided transepithelial PRK with intracorneal ring segments implantation and CXL in a three-step procedure seems to be an effective, promising treatment sequence offering patients a functional visual acuity and ceasing progression of the ectatic disorder. A longer follow-up and larger case series are necessary to thoroughly evaluate safety, stability, and efficacy of this innovative procedure.

Comparison of Epi-LASIK and Off-Flap Epi-LASIK for the Treatment of Low and Moderate Myopia

PURPOSE To compare the early postoperative course and the 1-year clinical results of off-flap Epi-LASIK and Epi-LASIK for the treatment of low and moderate myopia. DESIGN Pilot double-masked, randomized, comparative study. PARTICIPANTS Fifty-six patients (112 myopic eyes). METHODS Epithelium was separated in all eyes with the use of Centurion SES epikeratome (Norwood Abbey EyeCare, Vic, Australia). The first eye treated and surgical method in the first eye were randomized. One eye of each patient underwent standard Epi-LASIK, whereas in the contralateral eye, the epithelial sheet was not retained on the photoablated stroma (off-flap Epi-LASIK eyes). Mean preoperative spherical equivalent was -3.50+/-1.22 diopters (D; range, -1.75 to -6.37 D) in Epi-LASIK eyes and -3.61+/-1.22 D (range, -1.50 to -6.50 D) in off-flap Epi-LASIK eyes (P>0.05, paired Student t test). Excimer laser corneal ablation was performed using the Allegretto 200Hz (Wavelight Laser Technologie AG, Erlangen, Germany). Patients were followed up daily until the epithelial healing was complete and at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURES Epithelial healing time, subjective pain score, and uncorrected visual acuity (UCVA) were evaluated during the first postoperative days. Uncorrected visual acuity, spherical equivalent refraction, best spectacle-corrected visual acuity, haze scores, and wavefront aberrations were recorded at all subsequent intervals. RESULTS Time of epithelial healing did not differ significantly in Epi-LASIK and off-flap Epi-LASIK eyes (4.76+/-0.84 days in Epi-LASIK eyes vs. 4.54+/-0.93 days in off-flap Epi-LASIK eyes). No significant difference in UCVA was found after the 2 techniques during the first postoperative days. Subjective pain score was lower in off-flap Epi-LASIK eyes at 2 postoperative hours, whereas no significant difference in pain scores was noted between the 2 techniques at the other intervals. There was no significant difference in spherical equivalent, line gain or loss, haze scores, and higher-order aberrations between Epi-LASIK and off-flap Epi-LASIK eyes at any interval. Uncorrected visual acuity was significantly better in Epi-LASIK eyes only at 6 months (-0.05+/-0.08 in Epi-LASIK eyes vs. 0.00+/-0.07 in off-flap Epi-LASIK eyes). Preoperative wavefront aberrations did not change significantly 1 year after either procedure. CONCLUSIONS Epi-LASIK and off-flap Epi-LASIK had equal visual and refractive results for the treatment of low and moderate myopia in this study. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Photorefractive keratectomy followed by same-day corneal collagen crosslinking after intrastromal corneal ring segment implantation for pellucid marginal degeneration

A 28-year-old man with progressive pellucid marginal degeneration (PMD) had photorefractive keratectomy (PRK) followed by same-day corneal collagen crosslinking (CXL) for progressive PMD 12 months after intrastromal corneal ring segment implantation (Intacs). No intraoperative or early postoperative complications occurred. Nine months postoperatively, the uncorrected distance visual acuity improved from finger counting to 20/63 and the corrected distance visual acuity improved from 20/40 to 20/25. Corneal topography revealed a significant improvement in keratometry (from 46.73/38.67 to 44.92/39.01), which remained stable during the 9-month follow-up period. Despite the encouraging results, longer follow-up is necessary to evaluate the outcomes of this approach.