Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

INTRODUCTION: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. MATERIALS AND METHODS: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. RESULTS: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (ß = 0.923;p = 0.031). CONCLUSION: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro.

AIM: Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids. METHODOLOGY: Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin-eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions. RESULTS: PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation. CONCLUSION: PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-free tissue engineering applications in regenerative dentistry.

Citation network analysis on keratoconus

Objective: The high incidence of keratoconus has caused its management, etiology, and pathogenesis to be controversial topics in the ophthalmology field. This study aims to analyze the relationship between the different publications and authors through citation networks, as well as to identify the research areas and determine the most cited article. Methods: The search for publications was carried out through the Web of Science database, using the term “Keratoconus” between 1900 and December 2022. The Citation Network Explorer and CiteSpace software were used for the publication analysis. Results: 9,655 publications were found, with 124,379 citations generated on the network. The year with the highest number of publications was 2021. The most cited publication was “Keratoconus” by Rabinowitz, published in 1998. Cluster function gave five groups of research areas about keratoconus: corneal signs and parameters, cross-linking efficiency and effects, clinical factors, keratoplasty, and treatment. Conclusions: The citation network offers an objective and comprehensive analysis of the papers on keratoconus. (AU)

Efficacy and Safety of the Modified Cretan Protocol in Patients with Post-LASIK Ectasia

Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE). Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment. Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 µm, and -0.21±0.63 µm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 µm, and -0.51±0.58 µm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up. Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.

Successful Collagen Crosslinking in a Patient With Keratoconus and Systemic Scleroderma.

Scleroderma is an autoimmune disease that affects connective tissue. Keratoconus (KC) is a rare ocular condition that may appear alongside scleroderma. Contact lenses are an essential visual aid for KC patients, especially in advanced cases. However, scleroderma patients may face difficulties using them due to finger-related disabilities. Corneal collagen cross-linking (CXL) is a crucial treatment used to prevent corneal thinning and visual deterioration in progressive KC. However, the potential trigger of corneal melt and delayed healing following CXL in KC patients with scleroderma is a matter of concern. We present a case of a patient with KC and scleroderma who underwent CXL without any complications.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions: theoretical basis.

Keratoconus is an ectatic condition characterized by gradual corneal thinning, corneal protrusion, progressive irregular astigmatism, corneal fibrosis, and visual impairment. The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages, gas-permeable rigid contact lenses, scleral lenses, implantation of intrastromal corneal ring or corneal transplants for most advanced stages. In keratoconus cases showing disease progression corneal collagen crosslinking (CXL) has been proven to be an effective, minimally invasive and safe procedure. CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation, resulting in stromal crosslinks formation. The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models, from the original Dresden protocol to the most recent developments in the technique, reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols. Finally, the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes collagen cross-linking and ECM stiffening to induce liver fibrosis.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) is a key collagen lysyl hydroxylase mediating the formation of collagen fiber and stabilized collagen cross-links, and has been identified in several forms of fibrosis. However, the potential role and regulatory mechanism of Plod2 in liver fibrosis remain unclear yet. Mouse liver fibrosis models were induced by injecting carbon tetrachloride (CCl4) intraperitoneally. The morphology and alignment of collagen was observed under transmission and scanning electron microscopy, and extracellular matrix (ECM) stiffness was measured by atomic force microscopy. Large amounts of densely packed fibrillar collagen fibers produced by myofibroblasts (MFs) were deposited in fibrotic liver of mice reaching very large diameters in the cross section, accompanied with ECM stiffening, which was positively correlated with collagen-crosslinking. The expression of Plod2 was dynamically up-regulated in fibrotic liver of mouse and human. In MFs transfection of Plod2 siRNA made collagen fibers more orderly and linear aligned which can be easily degraded and protected from ECM stiffness. Administration of Plod2 siRNA preventatively or therapeutically in CCl4 mice reduced the average size of collagen bundles in transverse section, increased collagen solubility, decreases the levels of crosslinking products hydroxylysylpyridinoline and lysylpyridinoline, prevented ECM stiffening and alleviated liver fibrosis. Altogether, Plod2 mediates the formation of stabilized profibrotic collagen cross-links in MFs, leading to the alteration of collagen solubility and ECM stiffness, and eventually aggravates liver fibrosis, which provide potential target for the treatment of liver disease.

Keratometric Outcomes after Simultaneous versus Sequential Intracorneal Ring Segment Implantation with Femtosecond Laser and Corneal Collagen Crosslinking in Egyptian Patients with Keratoconus and Ectasia.

Background: Keratoconus (KC) is degenerative corneal disorder, with central and paracentral thinning and corneal ectasia. For KC progressive cases, primary treatment included corneal collagen cross linking (CXL) to stabilize coning and intracorneal rings segment (ICRS) to correct visual acuity. Aim: The aim of the study is to assess efficacy and safety of ICRS and CXL on one session (Simultaneous) or two sessions (sequential) with maximum of 1 month apart. Patients and Methods: This Prospective Intervention Comparative research made at Armed forces hospital, Cairo, Egypt from January 2017 to December 2019. Forty patients (60 eyes) with mild to moderate KC were enrolled. Patients sorted into Simultaneous group includes 21 patients (30 eyes) undergo two procedures (ICRS then CXL) at the same session and Sequential group included 19 patients (30 eyes) undergo ICRS then CXL on two sessions with month apart. Patients followed up at end of 1st, 3rd, and 6th months. Assessment included changes in corrected corneal surface irregularities as minimum keratometric 1 (K1), maximum keratometric readings (K2), and mean keratometric (Km) readings. Results: Improvement of K1, K2, and Km in Simulations and Sequential groups achieved at end of 1st-, 3rd-, and 6th-month postoperative versus preoperative. Maximum improvement in Simulations and Sequential groups in K1 achieved at end of 6th and 1st months, in K2 at end of 3rd and 6th months and in Km at end of 1st and 3rd months. Conclusions: Combined ICRS and CXL act safely in one or two sessions and there are no statistically significant variations between results on both methods in keratometric readings.

Reactive Oxygen Species-Responsive Nanoparticles Toward Extracellular Matrix Normalization for Pancreatic Fibrosis Regression.

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

Advances in the Treatment of Keratoconus: Epithelial-On (EPI-On) Corneal-Collagen Cross-Linking (CXL) and CXL-Plus Procedures.

Keratoconus (KC) incidence is on the increase. The advent of corneal-collagen cross-linking (CXL) has revolutionized the management of KC. This systematic review looks at the efficacy and complications of two novel treatments within CXL: Epithelial-On (Epi-On) and CXL-plus procedures. Two separate literature searches were carried out up until July 1, 2021. Articles only published in the last two years were included to ensure that only the most recent articles were reviewed. A total of 15 articles were selected for this review. There were varied results regarding the efficacy of Epi-On. No significant difference was found between Epi-On and standard Epithelial-Off (Epi-Off) CXL. However, it was found that Epi-On was inferior to standard CXL in terms of reducing KMAX. There was a higher risk of progression in patients treated with Epi-On CXL, with an increased rate of patients requiring re-treatment due to the advancement of their KC. While some studies report CXL-plus procedures demonstrate long-term efficacy and safety, a considerable number of studies advise caution, reporting a significant deterioration in corrected distance visual acuity (CDVA). Consequently, a question persists regarding the safest and most efficacious approach, given the lack of robust large randomized controlled trials (RCTs) in the current literature.

Evaluation of Keratoconus Disease with Tear Cytokine and Chemokine Levels Before and After Corneal Cross-Linking Treatment.

OBJECTIVES: To compare tear cytokine and chemokine levels of keratoconus (KC) patients with controls to perceive etiology distinctly and to clarify the molecular changes after cross-linking (CXL). METHODS: Tear samples were gathered from 34 participants in this prospective study. Participants underwent anterior and posterior segment examinations with slit-lamp biomicroscopy. Patients were assessed by corneal topography before and 3 months after CXL. Flat (K1), steep (K2), and average keratometry (Kmean), cylinder (CYL), and central corneal thickness (CCT) values were evaluated. After 3 months from CXL, samples were re-collected, and comparisons were made with preoperative values. RESULTS: Levels of IFN-gamma, IL-8, IL-12, IL-17, TNF-α, IL-4 and IL-13 were detected higher in KC patients (p= 0.008, p= 0.047, p= 0.001, p= 0.001, p= 0.001, p= 0.001, p= 0.027, respectively). After CXL IL-4, IL-5, IL-6, IL-7, IL-8, TNF-α levels showed significant decrease (p= 0.005, p= 0.045, p= 0.010, p= 0.022, p= 0.001, p=0.002, respectively). As for the topographic measurements, postoperative CCT values were increased whereas Kmean reduced after CXL (p < 0.001, p = 0.015, respectively). (p= 0.001, p= 0.027, respectively).Our findings imply that inflammation plays a key role in the development of KC and that this link is influenced by CXL therapy.

Citation network analysis on keratoconus.

OBJECTIVE: The high incidence of keratoconus has caused its management, etiology, and pathogenesis to be controversial topics in the ophthalmology field. This study aims to analyze the relationship between the different publications and authors through citation networks, as well as to identify the research areas and determine the most cited article. METHODS: The search for publications was carried out through the Web of Science database, using the term "Keratoconus" between 1900 and December 2022. The Citation Network Explorer and CiteSpace software were used for the publication analysis. RESULTS: 9,655 publications were found, with 124,379 citations generated on the network. The year with the highest number of publications was 2021. The most cited publication was "Keratoconus" by Rabinowitz, published in 1998. Cluster function gave five groups of research areas about keratoconus: corneal signs and parameters, cross-linking efficiency and effects, clinical factors, keratoplasty, and treatment. CONCLUSIONS: The citation network offers an objective and comprehensive analysis of the papers on keratoconus.

Corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking for severe keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking(SC-A-TE-CXL)in the treatment of severe keratoconus.METHODS: Prospective before-after self-control study. A total of 10 cases(14 eyes)of severe keratoconus with the thinnest corneal thickness(including epithelium)less than 400 μm were collected from March 2019 to July 2022 at the ophthalmology department of Affiliated Eye Hospital of Nanjing Medical University. Among them, 8 males(12 eyes)and 2 females(2 eyes)were treated with SC-A-TE-CXL. Corneal curvature, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), the thinnest corneal thickness(TCT), central corneal thickness(CCT), non-contact intraocular pressure, endothelial cell density(ECD)and anterior or posterior elevations at the thinnest point before surgery and at 1, 3, 6 and 12 mo postoperatively were observed and recorded, as well as corneal cross-linking depth at 1 mo postoperatively.RESULTS: UCVA and BCVA at 1, 3, 6, and 12 mo after SC-A-TE-CXL were higher than those preoperatively, but there were no differences(F=0.793, P=0.535; F=0.783, P=0.542). K1, K2, Km and Kmax decreased at each time point postoperatively compared with those preoperatively, but there were no differences(F=0.627, P=0.574; F=1.264, P=0.296; F=0.727, P=0.520; F=1.115, P=0.359). Anterior and posterior elevations at the thinnest point both decreased compared with those preoperatively, but the differences were not statistically significant(F=1.046, P=0.359; F=1.164, P=0.337). The non-contact intraocular pressure at each time point postoperatively was higher than that preoperatively, but the differences were not statistically significant(F=0.814, P=0.522). There were no differences in CCT and TCT at any time points of the follow-ups compared with those preoperatively(F=0.931, P=0.453; F=0.782, P=0.542). There was no difference in ECD at 12 mo postoperatively versus preoperative value(t=1.266, P=0.228). At 1 mo postoperatively, anterior segment optical coherence tomography(AS-OCT)exhibited an increase of density in the anterior stroma, and there was a demarcation line with an average depth of 124.07±25.13 μm.CONCLUSION: SC-A-TE-CXL can be considered as a surgical treatment for severe keratoconus, which can delay the progression of severe keratoconus with high safety. However, the long-term efficacy of this treatment requires further observation.

Refractive surgical correction and treatment of keratoconus.

Keratoconus is an ectatic corneal disorder that causes severe vision loss. Surgical options allow us to correct, partially or totally, the induced refractive error. Intracorneal ring segments (ICRS) implantation represents a minimally invasive surgical option that improves visual acuity, with a high success rate and a low overall complication rate. Corneal allogenic ICRS consists of ring segments derived from allogenic eye bank-processed donor corneas. Selective topography-guided transepithelial photorefractive or phototherapeutic keratectomy combined with CXL is another way in selected cases to improve spectacles corrected distance visual acuity. The microphotoablative remodeling of the central corneal profile is generally planned by optimizing the optical zones and minimizing tissue consumption. Phakic intraocular lens (PIOL) implant is considered in patients with stable disease and acceptable anatomical requirements. The two types of pIOLs, depending on their implantation inside the eye, are anterior chamber-pIOLs, which fixate to the anterior surface of the iris by using a polymethomethacrolate claw at the two haptics, and posterior chamber-pIOLs. In patients with both cataracts and keratoconus, the correct IOL power is difficult to obtain due to the irregular corneal shape and K values. Toric IOL is recommended, but carefully judging the topography and the possible need of subsequent keratoplasties.

Paediatric cornea crosslinking current strategies: A review.

Background: In the general population, 1 in 2000 people has keratoconus. Indians and other people from Southeast Asia have a higher incidence of keratoconus. Children with keratoconus typically present earlier in life and with a more severe disease. Rubbing the eyes has been identified as a risk factor. Children have a higher incidence and a faster rate of keratoconus progression. Visual rehabilitation in children with keratoconus is challenging. They have a low compliance with contact lens use. Many of these children require penetrating keratoplasty at an early age. Therefore, stopping the progression of keratoconus in children is of paramount importance. Main text: Compared to treatment, keratoconus progression prophylaxis is not only preferable, but also easier. Corneal collagen cross-linking has been shown to be safe and effective in stopping its progression in children. The Dresden protocol, which involves central corneal deepithelization (7-9 â€‹mm), saturation of the stroma with riboflavin (0.25%), and 30 â€‹min UV-A exposure, has proven to be the most successful. Two significant disadvantages of the typical Dresden regimen are the prolonged operating time and the significant post-operative pain. Accelerated-CXL (9 â€‹mW/cm2 x 10 â€‹min) has been studied to reduce operative time and has been shown to be equally effective in some studies. Compared to accelerated CXL or traditional CXL, epi-off procedures, transepithelial treatment without the need for de-epithelialization and without postoperative discomfort, have been shown to be safer but less effective. Corneal crosslinking should only be performed after treating children with active vernal keratoconjunctivitis. Corneal opacity, chronic corneal edema, sterile infiltrates, and microbial keratitis have been reported after cross-linking of corneal collagen. Conclusions: The "Dresden protocol", also known as the conventional corneal cross-linking approach, should be used to halt the progression of keratoconus in young patients. However, if the procedure needs to be completed more rapidly, accelerated corneal crosslinking may be considered. Transepithelial corneal cross-linking has been proven to be less effective at stabilizing keratoconus, although being more safer.

Intraocular pressure after combined photorefractive keratectomy and corneal collagen cross-linking for keratoconus.

PURPOSE: The purpose of this prospective study was to evaluate the effect of combined photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) on intraocular pressure (IOP) in patients with keratoconus (KC). METHODS: We included 64 eyes of 34 patients (19 males and 15 females; age: 19-40y) with stages 1-2 keratoconus which had undergone combined wavefront-optimized photorefractive keratectomy and corneal collagen cross linking. Two other groups of patients were added as controls: the PRK group including 110 eyes of 57 patients (23 males and 34 females; age: 18-44y) which had undergone wavefront-optimized photorefractive keratectomy for myopic refractive errors, and the CXL group including 36 eyes of 23 patients (14 males and 9 females; age: 12-38y) with keratoconus, not filling the inclusion criteria for combined PRK and CXL, which had undergone corneal collagen cross-linking. IOP was recorded preoperatively and postoperatively at 3, 6 and 12 months follow-up visits. RESULTS: Preoperative IOP in both CXL (12.1 ± 2.53 mmHg) and PRK + CXL (13.2 ± 2.50 mmHg) groups was significantly lower than PRK group (15.8 ± 3.10 mmHg) (F = 30.505, p < 0.001). At 3 months postoperatively, IOP showed no statistically significant difference between the three studied groups (F = 1.821, p = 0.164). At 6 months postoperatively, IOP in the CXL group (14.6 ± 2.64 mmHg) was significantly higher than both PRK (13.4 ± 2.27 mmHg) and PRK + CXL (13.3 ± 2.62 mmHg) groups (F = 3.721, p = 0.026). At 12 months postoperatively, IOP in the CXL group (14.3 ± 2.69 mmHg) was significantly higher than the PRK group (13.2 ± 2.23 mmHg) and was higher than PRK + CXL group (13.3 ± 2.59 mmHg) although not statistically significant (F = 3.393, p = 0.035). Regarding the percent of change from preoperative IOP, a statistically significant difference between the three studied groups was detected at 3, 6 and 12 months postoperatively (H = 117.459, 109.303, 122.694 respectively, p < 0.001). The median percent of change from preoperative IOP in the PRK group was -16.7%, -15%, and -16.7%, in the CXL group was + 14.3%, + 19.4%, and + 19.1%, while in PRK + CXL group was 0% at 3, 6 and 12 months postoperatively. (Post-hoc power analysis 75%). CONCLUSIONS: Combined PRK and CXL in patients with KC shows no significant effect on IOP, in contrast to either procedure performed separately.

Application of modified aldehyde compounds in self-etching bonding of dentin.

OBJECTIVE: The aim of this study was to evaluate the ability of 4-formylphenyl acrylate (FA) to enhance the bond strength and stabilize the resin-dentin bonding interface of universal adhesives in self-etching mode over time. METHODS: Different concentrations of FA (1%, 3%, 5%, 7%, 9%) were prepared as primer. The optimal group was selected according to degree of conversion of 2 universal adhesives (Single Bond Universal (SBU)/All-Bond Universal (ABU)), and grouped according to the pre-treatment time (30s, 1min, 2min). The micro-tensile strength before and after 10,000 times thermocycling aging was used to evaluate the bonding performance. RESULTS: The 1min application of FA (5%) increased the conversion rate of the adhesive. The expressions of microtensile bond strength and nanoleakage in the FA treatment group did not decrease significantly compared with their immediate values even after 10,000 thermocycling of aging. In situ zymography results showed that the hydrolytic activity of endogenous proteins decreased significantly in FA-1min group. CONCLUSIONS: Treatment by FA primer can effectively enhance the bond stability at the bonding interface. CLINICAL RELEVANCE: FA can be used as a functional monomer in self-etching bonding system to dentin, which not only had high biocompatibility, but also can show good collagen cross-linking ability within clinically acceptable application time.

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.

Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis.

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.