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1.
Cool Crosslinking: Riboflavin at 4°C for Pain Management After Crosslinking for Keratoconus Patients, A Randomized Clinical Trial.
Toro-Giraldo, L, Morales Flores, N, Santana-Cruz, O, Ramirez-Miranda, A, Navas, A, Olivo-Payne, A, Lichtinger, A, Jimenez-Corona, A, Graue-Hernández, EO
Cornea. 2021;(1):1-4
Abstract
PURPOSE To explore corneal cooling as a method of pain management in corneal-accelerated collagen cross-linking. METHODS This was a prospective and interventional randomized clinical trial registered in the National Institutes of Health Clinical Trials through the identifier NCT030760770. The research was conducted at the Institute of Ophthalmology "Conde de Valenciana." A total of 98 patients were randomly assigned to one of the following 2 groups: cold riboflavin (4°C) group or control group (riboflavin at room temperature). The inclusion criteria were patients of any sex, older than 18 years of age with keratoconus diagnosis who needed management with cross-linking in both eyes because of the evidence of progression. The exclusion criteria were patients who had cross-linking without epithelial debridement, unilateral cross-linking, or any other ocular pathologies besides keratoconus and any cognitive incapacity that would make the understanding of the pain test difficult. The main outcome measures were pain, tearing, photophobia, foreign body sensation, and irritation. RESULTS At 2 hours post-op, pain in the case and control groups was 3.80 ± 3.00 and 8.08 ± 2.21 (P < 0.05), tearing was 1.56 ± 1.96 and 8.29 ± 2.42 (P < 0.05), photophobia was 5.44 ± 3.57 and 7.83 ± 2.64 (P < 0.05), foreign body sensation was 2.20 ± 2.78 and 6.54 ± 2.73 (P < 0.05), and irritation was 3.48 ± 2.98 and 6.79 ± 3.00 (P < 0.05), respectively. A statistical significant difference was maintained in pain values on day 1 (2.79 ± 3.09 and 4.91 ± 3.27 [P < 0.05]), 2 (2.54 ± 2.41 and 4.00 ± 2.43 [P < 0.05]), and 4 (0.45 ± 0.76 and 1.22 ± 1.67 [P < 0.05]). CONCLUSIONS This study demonstrated that pain and associated symptoms decreased significantly in the riboflavin 4°C group.
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2.
Corneal collagen cross-linking with and without simultaneous intrastromal corneal ring segment implantation: One-year pilot study.
Sharma, IP, Bakshi, R, Chaudhry, M
European journal of ophthalmology. 2021;(1):61-68
Abstract
AIM: The aim of this study was to assess and compare the visual, refractive, and topographic outcomes of keratoconic eyes treated with corneal collagen cross-linking combined with and without same day intrastromal corneal ring segment over the first 12 months. METHODS This prospective randomized study analyzed 38 eyes of 30 consecutive keratoconus patients aged 26.21 ± 6.97 (range = 15-41) years. A total of 20 eyes were treated with collagen cross-linking alone, and 18 eyes underwent collagen cross-linking combined with simultaneous femtosecond laser-assisted intrastromal corneal ring segment. Visual acuity, manifest refraction, and corneal topography (using a rotating Scheimpflug topographer) were assessed and compared between the two groups at baseline, 6, and 12 months. RESULTS On an average follow-up duration of 12.2 ± 0.50 (range = 11-13) months, both collagen cross-linking alone and collagen cross-linking with simultaneous intrastromal corneal ring segment implantation were effective. However, collagen cross-linking plus intrastromal corneal ring segment resulted in an additional improvement of uncorrected distance visual acuity of 0.16 (95% confidence interval = 0.01 to 0.32) logarithm of the minimum angle of resolution units (p = 0.035), cylindrical power by 1.16 D (95% confidence interval = 0.25 to 2.06, p = 0.014), and spherical equivalent by 1.40 D (95% confidence interval = -2.71 to -0.08, p = 0.038) at 1 year. During the study period, no serious intraoperative or postoperative complications were noted in either group. CONCLUSION One-year follow-up results suggest that collagen cross-linking with simultaneously combined intrastromal corneal ring segment implantation could yield an additive visual and refractive outcome. The combined procedure is safe and merits consideration for the treatment of progressive keratoconus to achieve better visual rehabilitation.
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3.
Cross-Linking Assisted Infection Reduction (CLAIR): A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Bacterial Keratitis.
Prajna, NV, Radhakrishnan, N, Lalitha, P, Rajaraman, R, Narayana, S, Austin, AF, Liu, Z, Keenan, JD, Porco, TC, Lietman, TM, et al
Cornea. 2021;(7):837-841
Abstract
PURPOSE To determine whether there is a benefit to adjuvant corneal cross-linking (CXL) for bacterial keratitis. METHODS This is an outcome-masked, randomized controlled clinical trial. Consecutive patients presenting with a smear-positive bacterial ulcer at Aravind Eye Hospitals at Madurai, Pondicherry, and Coimbatore in India were enrolled. Study eyes were randomized to topical moxifloxacin 0.5% or topical moxifloxacin 0.5% plus CXL. The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle corrected visual acuity at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 weeks and 3 months, infiltrate and/or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS Those randomized to CXL had 0.60 decreased odds of culture positivity at 24 hours (95% confidence interval [CI]: 0.10-3.50; P = 0.65), 0.9 logarithm of the minimum angle of resolution lines worse visual acuity (95% CI: -2.8 to 4.6; P = 0.63), and 0.41-mm larger scar size (95% CI: -0.48 to 1.30; P = 0.38) at 3 months. We note fewer corneal perforations or need for therapeutic penetrating keratoplasty in the CXL group. CONCLUSIONS We were unable to confirm a benefit to adjuvant CXL in the primary treatment of moderate bacterial keratitis. However, CXL may reduce culture positivity and complication rates; therefore, a larger trial to fully evaluate this is warranted. TRIAL REGISTRATION NCT02570321.
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4.
Standard and accelerated corneal cross-linking long-term results: A randomized clinical trial.
Hashemi, H, Mohebbi, M, Asgari, S
European journal of ophthalmology. 2020;(4):650-657
Abstract
PURPOSE To compare long-term results between accelerated and standard corneal cross-linking protocols in the treatment of progressive keratoconus and compare their effectiveness between central (cone in the central 3 mm) and peripheral (cone beyond 3 mm) cases. METHODS In this randomized clinical trial, we compared 31 eyes treated with accelerated corneal cross-linking (18 mW/cm2, 5 min) and 31 eyes treated with standard corneal cross-linking (3 mW/cm2, 30 min), 16 central and 11 peripheral keratoconus in each group. In this report, 4-year changes in vision, refraction, topography, corneal biomechanics, and corneal cell count were evaluated. RESULTS Uncorrected distance visual acuity improvement was better with standard corneal cross-linking (0.19 ± 0.30 logMAR) than accelerated corneal cross-linking (0.08 ± 0.35 logMAR), but the intergroup difference was not statistically significant (p = 0.283). Cylinder and spherical equivalent significantly increased similarly in both groups. Among topographic indices, anterior Kmax-3 mm showed more reduction in standard corneal cross-linking than accelerated corneal cross-linking (1.35 ± 1.39 vs 0.36 ± 1.10 D, p = 0.011). Anterior Kmax-8 mm reduced by 1.50 ± 1.82 and 0.37 ± 1.58 D in the standard corneal cross-linking and accelerated corneal cross-linking groups, respectively (p = 0.029). Compared to 18-month results, none of the indices at 4 years showed any significant intergroup difference (all p > 0.05). In cases with peripheral keratoconus, changes in anterior Kmax-3 mm (+0.03 ± 0.66 vs -1.17 ± 1.15 D, p = 0.012) and anterior Kmax-8 mm (+0.43 ± 1.09 vs -1.57 ± 1.40 D, p = 0.003) were greater with standard corneal cross-linking. In central cases, no significant intergroup difference was observed. CONCLUSION At 4 years after the procedure, standard corneal cross-linking offered better anterior corneal flattening in the center and periphery. These differences concerned cases of peripheral keratoconus, and the two protocols were similarly effective in central cases. Beyond the 18th month, the two protocols appeared to be similarly effective.
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5.
Randomized Control Trial on the Effectiveness of Collagen Cross-linking on Bullous Keratopathy.
Choy, BNK, Ng, ALK, Zhu, MM, Liu, CC, Xu, S, Lai, JSM
Cornea. 2020;(11):1341-1347
Abstract
PURPOSE To investigate the long-term effect and safety of collagen cross-linking (CXL) on patients with bullous keratopathy (BK) in a randomized control manner. It is, to our knowledge, the first randomized control study on the effect of CXL on BK. METHODS Subjects were randomized to receive CXL as in the standard protocol for treating keratoconus or a placebo treatment. Subjects were assessed at baseline and up to 12 months after treatment. Primary outcomes were central corneal thickness (CCT) and pain scores. RESULTS Forty-two patients with BK participated in the study treatment, 26 subjects were randomized to the CXL group and 16 subjects to the control group. The reduction of CCT in the CXL group was 37.6 and 63.8 μm at 2 and 4 weeks, respectively, which were significantly higher than that in the control group. However, there was no statistical difference in CCT reduction between the 2 groups at 12 weeks and after. There were no consistent advantages in pain score, corneal clarity, and visual acuity over the controls throughout the 1-year follow-up. However, CXL was associated with more recurrent epithelial defect (12%), and 2 of the 3 subjects with epithelial defect required amniotic membrane transplant. CONCLUSIONS CXL reduced corneal thickness in the patients with BK, at least for the initial period. However, there were no improvement in pain, corneal clarity, and vision that were of more clinical relevance to the patients. Its short-term benefit was unlikely to outweigh its potential risk of recurrent epithelial defect.
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6.
Randomized Study of Collagen Cross-Linking With Conventional Versus Accelerated UVA Irradiation Using Riboflavin With Hydroxypropyl Methylcellulose: Two-Year Results.
Hagem, AM, Thorsrud, A, Sandvik, GF, Drolsum, L
Cornea. 2019;(2):203-209
Abstract
PURPOSE To compare the clinical outcome 2 years after corneal collagen cross-linking (CXL) with conventional and accelerated ultraviolet A (UVA) irradiation using riboflavin with hydroxypropyl methylcellulose. METHODS Prospective randomized controlled study. Forty patients with keratoconus (40 eyes) were randomized to either CXL using conventional 3 mW/cm UVA irradiation for 30 minutes (CXL30 group) or accelerated 9 mW/cm UVA irradiation for 10 minutes (CXL10 group). In both groups, a solution of 0.1% riboflavin with 1.1% hydroxypropyl methylcellulose (methylcellulose-riboflavin) was used. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and Scheimpflug tomography were performed at baseline and after 24 months. RESULTS Both groups had statistically significant improvement in CDVA and maximum keratometric reading compared with baseline; however, with no statistically significant difference in the change between the 2 groups. No significant changes in flattest, steepest and mean keratometry (K1, K2 and K mean) were found in either of the groups. There were no statistically significant changes in ECD in either group after 2 years or in the difference in the change between the 2 groups. A literature review showed comparative clinical outcome after accelerated CXL compared with conventional CXL; however, in several studies, there was a tendency for less pronounced corneal flattening after accelerated CXL. CONCLUSIONS Improvement in visual acuity and maximum keratometric reading 2 years after CXL was found after both conventional and accelerated UVA irradiation using methylcellulose-riboflavin. This suggests that when using riboflavin with methylcellulose, the less time-consuming accelerated protocol is a valuable and effective option in CXL treatment.
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7.
Antimicrobial photodynamic therapy (aPDT) with curcumin and LED, as an enhancement to scaling and root planing in the treatment of residual pockets in diabetic patients: A randomized and controlled split-mouth clinical trial.
Ivanaga, CA, Miessi, DMJ, Nuernberg, MAA, Claudio, MM, Garcia, VG, Theodoro, LH
Photodiagnosis and photodynamic therapy. 2019;:388-395
Abstract
INTRODUCTION Residual pockets represent a risk factor for periodontal disease progression. Diabetes Mellitus (DM) may impair prognosis after cause-related therapy, mainly due to the chronic hyperglycemia that negatively influences tissue repair. This study evaluated the clinical efficacy of antimicrobial photodynamic therapy (aPDT) with curcumin (CUR) solution (100 mg/L) and LED irradiation (465-485 nm), as an adjunctive therapy to scaling and root planing (SRP), in the treatment of residual pockets in type 2 diabetic patients. METHODS Individuals with type 2 DM and chronic periodontitis presenting at least one residual pocket per quadrant were selected (n = 25). In each patient, all residual pockets with probing depth (PD) ≥5 mm and bleeding on probing (BOP) were allocated to receive, according to quadrant: 1) SRP (SRP group); 2) SRP and irrigation with CUR solution (100 mg/L) (CUR group); 3) SRP and LED irradiation (InGaN, 465-485 nm, 0.78 cm², 78 mW, 100 mW/cm², 60 s) (LED group); 4) SRP, irrigation with CUR solution (100 mg/L), one minute of pre-irradiation, and LED irradiation (InGaN, 465-485 nm, 60 s) (aPDT group). Clinical parameters of PD, gingival recession (GR), clinical attachment level (CAL), BOP and visible plaque index (PI) were evaluated at baseline, three and six months post-therapies. Differences between the examination periods in each group were analyzed by Friedman's test for non-parametric data, while parametric data were submitted to analysis of variance (One-way ANOVA), followed by Tukey's test. Intergroup comparisons were performed by Kruskal-Wallis test. RESULTS In an intergroup comparison, the mean values for PD, GR, CAL, BOP and PI were not different at baseline, three and six months (p > 0.05). The intragroup comparison evidenced reduction in PD and BOP in all treatment groups at three and six months (p < 0.05). Significant CAL gain was notable only for the aPDT and LED groups at three months in comparison to baseline data (p < 0.05). CONCLUSION Treatment of residual pockets in patients with type 2 DM through association of SRP with aPDT (CUR solution 100 mg/L and LED irradiation) or LED irradiation may yield short-term (three months) clinical benefits regarding CAL gain.
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8.
Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing Frequencies for Treatment of Keratoconus and Corneal Ectasia.
Price, MO, Fairchild, K, Feng, MT, Price, FW
Ophthalmology. 2018;(4):505-511
Abstract
PURPOSE To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN Prospective, randomized, single-center equivalence trial. PARTICIPANTS Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.
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9.
Epithelial remodeling after corneal crosslinking using higher fluence and accelerated treatment time.
Haberman, ID, Lang, PZ, Broncano, AF, Kim, SW, Hafezi, F, Randleman, JB
Journal of cataract and refractive surgery. 2018;(3):306-312
Abstract
PURPOSE To evaluate changes in regional corneal epithelial thickness after corneal crosslinking (CXL) using higher fluence (7.2 J/cm2) and accelerated treatment time (4 minutes) in eyes with progressive keratoconus using spectral-domain optical coherence tomography (SD-OCT) and to correlate focal epithelial and focal anterior curvature changes. SETTING Academic medical center in the United States. DESIGN Prospective case series. METHODS Patients had anterior segment SD-OCT (RTVue-100) with focal stromal and epithelial measurements and Scheimpflug imaging before and 1, 3, 6, and 12 months after accelerated CXL. RESULTS Twenty-seven eyes from 20 patients were evaluated. Before the accelerated CXL, the epithelium was thinnest in the inferior inner and outer temporal regions, whereas at 12 months postoperatively, the epithelium was significantly thinned in multiple inferior and nasal regions by 1.1 to 3.2 μm (P < .05, all measurements), with no significant changes from 6 to 12 months. Epithelial thickness standard deviation across the central 6.0 mm was significantly reduced by 3 months (1.4 μm, P = .09) and remained stable at 12 months (P = .009). Change in epithelial thickness was poorly correlated to change in anterior curvature (r = -0.035). CONCLUSIONS Significant epithelial remodeling occurred after accelerated CXL in eyes with progressive keratoconus, with improved regularity across the central 6.0 mm, by 6 months after treatment. There was poor correlation between focal epithelial thickness and anterior curvature changes, with wide variability between patients. Establishing the pattern of epithelial remodeling after CXL might help optimize future custom treatment protocols.
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10.
Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study.
Sadoughi, MM, Einollahi, B, Baradaran-Rafii, A, Roshandel, D, Hasani, H, Nazeri, M
International ophthalmology. 2018;(1):67-74
Abstract
PURPOSE To compare the outcomes of the conventional and accelerated corneal collagen cross-linking (CXL) in patients with bilateral progressive keratoconus (KC). METHODS Fifteen consecutive patients with bilateral progressive KC were enrolled. In each patient, the fellow eyes were randomly assigned to the conventional CXL (3 mW/cm2 for 30 min) or accelerated CXL (ACXL) (9 mW/cm2 for 10 min) groups. Manifest refraction; uncorrected and corrected distant visual acuity; maximum and mean keratometry; corneal hysteresis and corneal resistance factor; endothelial cell density and morphology; central corneal thickness; and wavefront aberrations were measured before and 12 months after the CXL. RESULTS Manifest refraction spherical equivalent and refractive cylinder improved significantly only in conventional group. Uncorrected and corrected distant visual acuity did not change significantly in either group. Also there was no significant change in the maximum and mean keratometry after 12 months. There was significant decrease in central corneal thickness in both groups which was more prominent in conventional group. Endothelial cell density reduced only in the conventional group which was not statistically significant (P = 0.147). CH, CRF, and wavefront aberrations did not change significantly in either group. We did not observe any significant difference in the changes of the variables between the two groups. CONCLUSIONS Accelerated CXL with 9 mW/cm2 irradiation for 10 min had similar refractive, visual, keratometric, and aberrometric results and less adverse effects on the corneal thickness and endothelial cells as compared with the conventional method after 12 months follow-up. However, randomized clinical trials with longer follow-ups and larger sample sizes are needed.