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.


Keratoconus is a noninflammatory corneal disorder characterized by progressive thinning, irregular steepening of the cornea, and apical scarring causing gradual loss of visual acuity. Corneal collagen cross-linking (CXL) is a minimally invasive surgical treatment used to strengthen the tissue of the ectatic cornea and arrest keratoconus progression. Standard CXL procedure involves 30 minutes of ultraviolet-A (UV-A) irradiation at an intended irradiance of 3.0 mW/cm 2 with total surface dose of 5.4 J/cm 2 (Dresden protocol).


According to the photochemical law of reciprocity (Bunsen-Roscoe law), the same photochemical effect is achieved with reduced illumination time and correspondingly increased irradiation intensity, meaning that a 10-minute irradiation at 9.0 mW/cm 2 should provide the same effect with a 30-minute irradiation at 3.0 mW/cm 2 . Several new CXL devices offer high UV-A irradiation intensity with relevant time settings.


After CXL, a corneal stromal demarcation line is detectable on slit-lamp examination at as early as 2 weeks at a depth of approximately 300 μm. Corneal stromal demarcation line after CXL can be equally detected using confocal microscopy and anterior segment optical coherence tomography (AS-OCT), possibly representing the effectiveness of the CXL treatment.


Recently we evaluated the corneal stromal demarcation line depth of 2 different protocols; the accelerated protocol of 10 minutes with UV-A irradiation intensity of 9 mW/cm 2 provided significantly shallower effect than with the standard Dresden protocol of 30 minutes with 3 mW/cm 2 irradiation intensity.


The purpose of this study was to evaluate and compare the depth of the corneal stromal demarcation line using AS-OCT with 2 different treatment protocols: the standard Dresden CXL protocol (30 minutes with 3 mW/cm 2 ) vs our modified-accelerated CXL protocol (14 minutes with 9 mW/cm 2 ) using the same high-intensity UV-A irradiation device (CCL-365; Peschke Meditrade GmbH, Huenenberg, Switzerland).


Patients and Methods


Patient Population


In this prospective, comparative study 43 patients (34 male and 9 female; 52 eyes) with progressive keratoconus were enrolled. The clinical diagnosis of keratoconus was based on corneal topography data (iTrace; Tracey Technologies, Houston, Texas, USA). Inclusion criteria were progressive keratoconus, patient age older than 18 years, corneal thickness more than 400 μm, no other ocular pathologic signs, and no pregnancy or lactation. Keratoconus was graded with the Amsler-Krumeich classification; only patients with grade I and II were included in this study.


All patients underwent uneventful CXL treatment with the use of a new high-intensity UV-A illuminator (CCL-365; Peschke Meditrade GmbH, Huenenberg, Switzerland). The selection of the CXL irradiation treatment protocol was made alternately; 26 eyes were treated for 30 minutes in an intended irradiance of 3.0 mW/cm 2 according to the Dresden protocol (Group 1), while 26 eyes were treated for 14 minutes in an intended irradiance of 9.0 mW/cm 2 (Group2).


Data obtained from the patient records included age, sex, preoperative ultrasound corneal pachymetry (Corneo-Gage Plus; Sonogage Inc, Cleveland, Ohio, USA), preoperative keratometry readings, endothelial cell density (ECD), and AS-OCT scans (Visante OCT 3.0; Carl Zeiss Meditec Inc, Jena, Germany).


Institutional Review Board approval from the University of Crete was obtained and all patients were appropriately informed before their participation in the study and gave written informed consent in accordance with institutional guidelines, according to the Declaration of Helsinki.


Surgical Technique


All procedures were performed by the same surgeon (G.D.K.) under sterile conditions. After topical anesthesia with proxymetacaine hydrochloride 0.5% eye drops (Alcaine; Alcon Laboratories, Inc, Fort Worth, Texas, USA), corneal epithelium was mechanically removed using a rotating brush within an 8.0–9.0 mm diameter. After epithelial removal, riboflavin (0.1% solution of 10 mg riboflavin-5-phosphate in 10 mL dextran-T-500 20% solution; Medicross; Medio-Haus, Behrensbrook, Neudorf, Germany) was instilled on the center of the cornea every 3 minutes for approximately 30 minutes in both groups. UV-A irradiation was performed using a new high-intensity UV-A optical system (CCL-365; Peschke Meditrade GmbH, Huenenberg, Switzerland). Before treatment, an intended irradiance of 3.0 mW/cm 2 (Group 1) or 9.0 mW/cm 2 (Group 2) was calibrated using the UV-A light meter YK-35UV (Lutron Electronic, Coopersburg, Pennsylvania, USA), which is supplied with the UV-X device. In Group 1, UV-A irradiance was performed for 30 minutes according to standard Dresden protocol in an intended irradiance of 3.0 mW/cm 2 , while in Group 2 (modified-accelerated protocol) it was performed for 14 minutes in an intended irradiance of 9.0 mW/cm 2 , corresponding to a total surface dose of 5.4 J/cm 2 and 7.5 J/cm 2 , respectively. During UV-A irradiation, riboflavin solution was applied every 3 minutes to maintain corneal riboflavin saturation. At the end of the procedure, a silicone-hydrogel bandage contact lens (14.0 mm in diameter, 8.6 base curvature, Dk = 140 barrers; lotrafilcon B, Air Optix; Alcon Laboratories Inc, Fort Worth, Texas, USA) was applied until full re-epithelialization.


Postoperative medication included chloramphenicol/dexamethasone drops (Dispersadron; Thea Laboratories, Inc, Clermont-Ferrand, France) 4 times daily until the removal of the bandage contact lens. After the removal of the contact lens, patients received corticosteroid drops 4 times daily (FML, fluorometholone 0.1%; Falcon Pharmaceuticals, Fort Worth, Texas, USA) with tapering for the next 3 weeks. Patients were encouraged to use artificial tears at least 6 times per day for at least 3 months postoperatively.


Anterior Segment Optical Coherence Tomography


All scans were performed under the same light conditions, 1 month postoperatively. All patients were asked to fixate on the optical target of the system. The image was captured when the corneal reflex, a vertical white line along the center of the cornea, was visible. The high-resolution corneal scan was used to produce an enhanced image of the cornea on the horizontal meridian (0–180 degrees). The stromal demarcation line was identified in the enhanced corneal image, and the demarcation line depth was measured using the flap tool, as provided by the manufacturer. The demarcation line depth was measured by 2 independent observers (K.T. and M.G.) in the center of the cornea. The visibility of the demarcation line was scored to obtain accuracy of the measurements (0 = line not visible; 1 = line visible, but measurement not very accurate; 2 = line clearly visible). Only measurements with score 2 were included in the study.


Statistical Analysis


All data were recorded into an Excel spreadsheet database (Microsoft, Redmond, Washington, USA) and statistical analysis was performed using SPSS for Windows, version 20 (SPSS, Inc, Chicago, Illinois, USA). A sample size analysis (G*Power 3.1.3; Franz Paul, Universitat Kiel, Kiel, Germany) was performed for a 2-tailed t test with a large difference effect size, statistical power of 80%, and statistical significance level of .05, resulting in 26 patients participating in each group in this prospective study. Normality of distribution of all measurements was confirmed using the Shapiro-Wilk test, appropriate for small sample sizes of fewer than 50 participants. To avoid bias and ensure the comparability of the 2 groups, the baseline characteristics between the groups were compared. The Bland-Altman method was used to determine the agreement between the 2 observers. The limits of agreement were defined as the mean difference of 2 measurements ± 1.96 standard deviation of the difference. Paired t tests were performed between the measurements of the 2 observers to determine whether they differ statistically significantly. Continuous variables are presented as mean ± SD (minimum, maximum). A P value <.05 was considered statistically significant.




Results


Fifty-two eyes of 43 patients (34 male, 9 female; 26 eyes in each group) were included. The mean age of the patients was 26.15 ± 6.32 (range, 18–45) and 26.23 ± 6.90 (range, 18–46) for Group 1 and 2, respectively. Both groups were comparable in age, preoperative corneal pachymetry, and steep and flat keratometric readings ( Table ). There were no intraoperative or postoperative complications observed in any of the patients. The epithelium healing process completed at 4.63 ± 1.42 (range, 3–8) days in Group 1 and 4.14 ± 1.49 (range, 3–8) days in Group 2. There was no statistically significant difference in the duration of epithelial wound healing in both groups ( P = .297).


Jan 8, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Evaluation of Corneal Stromal Demarcation Line Depth Following Standard and a Modified-Accelerated Collagen Cross-linking Protocol
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