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1.
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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2.
Accelerated Versus Standard Corneal Cross-Linking for Progressive Keratoconus: A Meta-Analysis of Randomized Controlled Trials.
Kobashi, H, Tsubota, K
Cornea. 2020;(2):172-180
Abstract
PURPOSE To compare the clinical results of accelerated corneal collagen cross-linking (ACXL) to standard corneal collagen cross-linking (SCXL) in progressive keratoconus by summarizing randomized controlled trials using a meta-analysis. METHODS Trials meeting the selection criteria were quality appraised, and data were extracted by 2 independent authors. A comprehensive search was performed using the Cochrane methodology to evaluate the clinical outcomes of ACXL and SCXL for treating progressive keratoconus. Estimates were evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for absolute changes of the outcomes during 12-month observation periods. Postoperative demarcation line depth was also compared. RESULTS We identified 6 randomized controlled trials that met the eligibility criteria for this meta-analysis. SCXL resulted in a significantly better outcome in postoperative changes in best spectacle-corrected visual acuity (WMD = -0.02; 95% CI, -0.03 to -0.01; P < 0.0001); however, the small differences may not be clinically significant. ACXL provided a significantly better improvement of cylindrical refraction after the 1-year follow-up (WMD = 0.15; 95% CI, 0.05-0.26; P = 0.005). Demarcation line depth at 1 month after SCXL was deeper than that after ACXL (WMD = -102.25; 95% CI, -157.16 to -47.35; P = 0.0003). No differences in the changes in maximum keratometry, central corneal thickness, uncorrected visual acuity, spherical equivalent refraction, corneal biomechanical properties, and corneal endothelial cell density were found among both groups. CONCLUSIONS An ACXL shows a comparable efficacy and safety profile at the 1-year follow-up, but it has less impact on improving best spectacle-corrected visual acuity when compared with the Dresden protocol. Overall, both methods similarly stop the disease progression.
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3.
Corneal collagen cross-linking for bacterial infectious keratitis.
Davis, SA, Bovelle, R, Han, G, Kwagyan, J
The Cochrane database of systematic reviews. 2020;(6):CD013001
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Abstract
BACKGROUND Infectious keratitis is an infection of the cornea that can be caused by bacteria, viruses, fungi, protozoa, or parasites. It may be associated with ocular surgery, trauma, contact lens wear, or conditions that cause deficiency or loss of corneal sensation, or suppression of the immune system, such as diabetes, chronic use of topical steroids, or immunomodulatory therapies. Photoactivated chromophore for collagen cross-linking (PACK-CXL) of the cornea is a therapy that has been successful in treating eye conditions such as keratoconus and corneal ectasia. More recently, PACK-CXL has been explored as a treatment option for infectious keratitis. OBJECTIVES To determine the comparative effectiveness and safety of PACK-CXL with standard therapy versus standard therapy alone for the treatment of bacterial keratitis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 7); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 8 July 2019. SELECTION CRITERIA We included randomized controlled trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) of PACK-CXL for bacterial keratitis. We included quasi-RCTs and CCTs as we anticipated that there would not be many RCTs eligible for inclusion. DATA COLLECTION AND ANALYSIS Two review authors working independently selected studies for inclusion in the review, assessed trials for risk of bias, and extracted data. The primary outcome was proportion of participants with complete healing at four to eight weeks. Secondary outcomes included visual acuity, morphology, adverse events, and treatment failure at four to eight weeks. MAIN RESULTS We included three trials (two RCTs and one quasi-RCT) in this review for a total of 59 participants (59 eyes) with bacterial keratitis. Trials were all single-center and were conducted in Egypt, Iran, and Thailand between 2010 and 2014. It is very uncertain whether PACK-CXL with standard antibiotic therapy is more effective than standard antibiotic therapy alone for re-epithelialization and complete healing (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.88 to 2.66; participants = 15). We judged the certainty of the evidence to be very low due to the small sample size and high risk of selection and performance bias. The high risk of selection bias reflects the overall review. Masking of participants was not possible for the surgical arm. No participant had a best-corrected visual acuity of 20/100 or better at eight weeks (very low certainty evidence). There is also no evidence that use of PACK-CXL with standard therapy results in fewer instances of treatment failure than standard therapy alone (RR 0.50, 95% CI 0.05 to 4.98; participants = 32). We judged the certainty of evidence to be low due to the small sample size and high risk of selection bias. There were no adverse events reported at 14 days (low certainty evidence). Data on other outcomes, such as visual acuity and morphological characteristics, could not be compared because of variable time points and specific metrics. AUTHORS' CONCLUSIONS The current evidence on the effectiveness of PACK-CXL for bacterial keratitis is of low certainty and clinically heterogenous in regard to outcomes. There are five ongoing RCTs enrolling 1136 participants that may provide better answers in the next update of this review. Any future research should include subgroup analyses based on etiology. A core outcomes set would benefit healthcare decision-makers in comparing and understanding study data.
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Corneal refractive surgery combined with simultaneous corneal cross-linking: Indications, protocols and clinical outcomes-A review.
Ma, J, Wang, Y, Jhanji, V
Clinical & experimental ophthalmology. 2020;(1):78-88
Abstract
Corneal refractive surgery is one of the most common approaches for correction of refractive errors. Combined corneal refractive surgery and corneal cross-linking (CXL) has been proposed as a method to achieve better refractive stability and to prevent iatrogenic corneal ectasia. However, there are concerns regarding its indications, surgical safety, standardization of protocols and long-term effect on corneal tissue. This review article aims to discuss the current knowledge and recent updates on combination of CXL and refractive surgery.
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5.
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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Theoretical and Experimental Studies on the Near-Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye: Photoinduced Hydrolysis by Radical Anion Generation.
Kobayashi, M, Harada, M, Takakura, H, Ando, K, Goto, Y, Tsuneda, T, Ogawa, M, Taketsugu, T
ChemPlusChem. 2020;(9):1953
Abstract
Invited for this month's cover are the collaborating groups of Dr. Masato Kobayashi and Prof. Mikako Ogawa, both from Hokkaido University, Sapporo, Japan. The cover picture shows the photochemical reaction process of the near-infrared (NIR) photoimmunotherapy dye IR700, and subsequent cancer cell death. A computational study predicted that ligand dissociation, which is known to initiate cancer cell death, proceeds by the hydrolysis of the IR700 radical anion, rather than as a direct result of NIR irradiation. This mechanism has also been supported by experimental work. Read the full text of the Communication at 10.1002/cplu.202000338.
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The odyssey of cobaloximes for catalytic H2 production and their recent revival with enzyme-inspired design.
Dolui, D, Khandelwal, S, Majumder, P, Dutta, A
Chemical communications (Cambridge, England). 2020;(59):8166-8181
Abstract
Cobaloxime complexes gained attention for their intrinsic ability of catalytic H2 production despite their initial emergence as a vitamin B12 model. The simple, robust, and synthetically manoeuvrable cobaloxime core represents a model catalyst molecule for the investigation of optimal conditions for both photo- and electrocatalytic H2 production catalytic assemblies. Cobaloxime is one of the rare catalysts that finds equal applications in the analysis of homogeneous and heterogeneous catalytic conditions. However, the poor aqueous solubility and long-term instability of cobaloximes have severely impeded their growth. Lately, interest in the cobaloxime-based catalysts has been resuscitated with the rational use of extended enzymatic features. This unique enzyme-inspired catalyst design strategy has instigated the formation of a new genre of cobaloxime molecules that exhibit enhanced photo- and electrocatalytic H2 evolution with improved aqueous and air stability.
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Theoretical and Experimental Studies on the Near-Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye: Photoinduced Hydrolysis by Radical Anion Generation.
Kobayashi, M, Harada, M, Takakura, H, Ando, K, Goto, Y, Tsuneda, T, Ogawa, M, Taketsugu, T
ChemPlusChem. 2020;(9):1959-1963
Abstract
Ligand release from IR700, a silicon phthalocyanine dye used in near-infrared (NIR) photoimmunotherapy, initiates cancer cell death after NIR absorption, although its photochemical mechanism has remained unclear. This theoretical study reveals that the direct Si-ligand dissociation by NIR light is difficult to activate because of the high dissociation energy even in excited states, i. e., >1.30 eV. Instead, irradiation generates the IR700 radical anion, leading to acid-base reactions with nearby water molecules (i. e., calculated pKb for the radical anion is 7.7) to produce hydrophobic ligand-released dyes. This suggests two possibilities: (1) water molecules participate in ligand release and (2) light is not required for Si-ligand dissociation as formation of the IR700 radical anion is sufficient. Experimental evidence confirmed possibility (1) by using 18 O-labeled water as the solvent, while (2) is supported by the pH dependence of ligand exchange, providing a complete description of the Si-ligand bond dissociation mechanism.
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Antimicrobial photodynamic therapy effectiveness against susceptible and methicillin-resistant Staphylococcus aureus biofilms.
Teixeira, CGS, Sanitá, PV, Ribeiro, APD, Dias, LM, Jorge, JH, Pavarina, AC
Photodiagnosis and photodynamic therapy. 2020;:101760
Abstract
BACKGROUND Staphylococcus aureus have a great ability to become rapidly resistant to conventional antimicrobial therapies. This study evaluated the efficacy of antimicrobial photodynamic therapy (aPDT) mediated by Curcumin (Cur) and light-emitting diode (LED) in the inactivation of biofilms of methicillin susceptible and resistant S. aureus (MSSA and MRSA, respectively). METHODS Biofilms were treated with Cur (20, 40 or 80 μM) and illuminated with LED source (455 ± 3 nm; 5.28 J/cm2) (aPDT groups), or treated either with Cur or LED only. Other samples were not exposed to Cur or LED (negative control). The biofilms viability after all experimental conditions were evaluated by counting the number of colonies (CFU/mL) and XTT assay. Additional samples were also evaluated by LIVE/DEAD® staining using confocal laser scanning microscopy (CLSM). Data were analyzed by ANOVAs followed by the Games-Howell post hoc test (α = 0.05). RESULTS For both strains, all aPDT groups significantly reduced both CFU/mL and metabolic activity of biofilms compared to the negative control (p < 0.001). The results were enhanced when 80 μM of Cur was used. CLSM images showed that both bacteria biofilms submitted to aPDT had a large number of red-stained colonies, especially at aPDT80. In general, MRSA biofilms tended to be less susceptible to aPDT than MSSA biofilms. CONCLUSIONS It can be concluded that aPDT mediated by Cur and LED was an efficient method to inactivate 48 -h biofilms of both S. aureus strains.
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Advantages of salvage photodynamic therapy using talaporfin sodium for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.
Minamide, T, Yoda, Y, Hori, K, Shinmura, K, Oono, Y, Ikematsu, H, Yano, T
Surgical endoscopy. 2020;(2):899-906
Abstract
BACKGROUND Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT). METHODS We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled. RESULTS A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]). CONCLUSIONS L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.