Hyperbaric Oxygenation Maintains Elevated Stromal Oxygen Availability During Corneal Collagen Crosslinking with and Without Epithelial Removal.

PURPOSE: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL. METHODS: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing. RESULTS: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups. CONCLUSIONS: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed.

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.

The impact of interrupted corneal collagen crosslinking (CXL) treatment.

PURPOSE: To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea. METHODS: A retrospective review was conducted of all patients with keratoconus diagnosis who underwent CXL at the Department of Ophthalmology, Örebro University Hospital (USÖ) during the years 2010-2017. In total 377 eyes of 280 patients were screened for inclusion. In 17 eyes (15 patients), the treatment was interrupted due to insufficient swelling of the cornea. Patient journals were reviewed and keratometry examinations were analysed for long-term progression. RESULTS: Eleven eyes (nine patients) were included in the study. Five eyes showed no signs of progression after the interrupted CXL treatment. In one eye progression continued, however, first after a period of a number of years, indicating a delayed course of clinical progression. CONCLUSION: This study indicates that debridement of the corneal epithelium and riboflavin administration without intense UVA radiation may slow or arrest the progression of keratoconus, likely due to photosensitisation from ambient light.

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.

Periostin regulates lysyl oxidase through ERK1/2 MAPK-dependent serum response factor in activated cardiac fibroblasts.

Collagen crosslinking, mediated by lysyl oxidase, is an adaptive mechanism of the cardiac repair process initiated by cardiac fibroblasts postmyocardial injury. However, excessive crosslinking leads to cardiac wall stiffening, which impairs the contractile properties of the left ventricle and leads to heart failure. In this study, we investigated the role of periostin, a matricellular protein, in the regulation of lysyl oxidase in cardiac fibroblasts in response to angiotensin II and TGFß1. Our results indicated that periostin silencing abolished the angiotensin II and TGFß1-mediated upregulation of lysyl oxidase. Furthermore, the attenuation of periostin expression resulted in a notable reduction in the activity of lysyl oxidase. Downstream of periostin, ERK1/2 MAPK signaling was found to be activated, which in turn transcriptionally upregulates the serum response factor to facilitate the enhanced expression of lysyl oxidase. The periostin-lysyl oxidase association was also positively correlated in an in vivo rat model of myocardial infarction. The expression of periostin and lysyl oxidase was upregulated in the collagen-rich fibrotic scar tissue of the left ventricle. Remarkably, echocardiography data showed a reduction in the left ventricular wall movement, ejection fraction, and fractional shortening, indicative of enhanced stiffening of the cardiac wall. These findings shed light on the mechanistic role of periostin in the collagen crosslinking initiated by activated cardiac fibroblasts. Our findings signify periostin as a possible therapeutic target to reduce excessive collagen crosslinking that contributes to the structural remodeling associated with heart failure.

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)

[Alternative methods of surgical treatment of keratoconus]. / Al'ternativnye metody khirurgicheskogo lecheniya keratokonusa.

The introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts. The described methods of treatment, according to the authors, are the most promising.

Lysyl Oxidase Production by Murine C3H10T1/2 Mesenchymal Stem Cells Is Increased by TGFßs and Differentially Modulated by Mechanical Stimuli.

Tendons are frequently injured and have limited regenerative capacity. This motivates tissue engineering efforts aimed at restoring tendon function through strategies to direct functional tendon formation. Generation of a crosslinked collagen matrix is paramount to forming mechanically functional tendon. However, it is unknown how lysyl oxidase (LOX), the primary mediator of enzymatic collagen crosslinking, is regulated by stem cells. This study investigates how multiple factors previously identified to promote tendon formation and healing (transforming growth factor [TGF]ß1 and TGFß2, mechanical stimuli, and hypoxia-inducible factor [HIF]-1α) regulate LOX production in the murine C3H10T1/2 mesenchymal stem cell (MSC) line. We hypothesized that TGFß signaling promotes LOX activity in C3H10T1/2 MSCs, which is regulated by both mechanical stimuli and HIF-1α activation. TGFß1 and TGFß2 increased LOX levels as a function of concentration and time. Inhibiting the TGFß type I receptor (TGFßRI) decreased TGFß2-induced LOX production by C3H10T1/2 MSCs. Low (5 mPa) and high (150 mPa) magnitudes of fluid shear stress were applied to test impacts of mechanical stimuli, but without TGFß2, loading alone did not alter LOX levels. Low loading (5 mPa) with TGFß2 increased LOX at 7 days greater than TGFß2 treatment alone. Neither HIF-1α knockdown (siRNA) nor activation (CoCl2) affected LOX levels. Ultimately, results suggest that TGFß2 and appropriate loading magnitudes contribute to LOX production by C3H10T1/2 MSCs. Potential application of these findings includes treatment with TGFß2 and appropriate mechanical stimuli to modulate LOX production by stem cells to ultimately control collagen matrix stiffening and support functional tendon formation.

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.

RiTe conjugate mediated corneal collagen crosslinking, a novel therapeutic intervention for keratoconus - in vitro and in vivo study.

Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues. The present study has employed cell penetrating peptide (CPP), Tat2, to enhance the penetration of riboflavin molecule, and thereby improve currently followed CXL protocol. This study demonstrates approximately two-fold enhanced uptake of CPP riboflavin conjugate, Tat2riboflavin-5'Phosphate (RiTe conjugate), both in vitro and in vivo. Two different CXL protocols (Epi ON and Epi OFF) have been introduced and implemented in rabbit corneas using RiTe conjugate in the present study. The standard and RiTe conjugate mediated CXL procedures exhibited an equivalent extent of crosslinking in both the methods. Reduced keratocyte loss and no endothelial damage in RiTe conjugate mediated CXL further ascertains the safety of the proposed CXL protocols. Therefore, RiTe conjugate mediated CXL protocols present as potential alternatives to the standard keratoconus treatment in providing equally effective, less invasive and patient compliant treatment modality.

The effect of transepithelial corneal collagen cross-linking treatment on optical quality of the cornea in keratoconus: 12-month clinical results.

PURPOSE: To evaluate the effect of transepithelial corneal collagen crosslinking (CXL) treatment on the optical performance of the cornea at 12-month follow-up after CXL in patients with progressive keratoconus. METHODS: One hundred and ten eyes of 67 patients were included. The following corneal optical aberrations over the 4-mm-diameter pupil were recorded via Sirius dual-scanning corneal tomography: total, anterior and posterior amount of corneal higher order aberrations [HOAs], vertical coma, horizontal coma, vertical trefoil, oblique trefoil, and spherical aberration, and Strehl ratio of point spread function (PSF). RESULTS: There were significant improvements in mean root mean square error values for corneal total HOA, total coma, anterior HOA, anterior coma, and vertical coma following CXL (P > 0.05, for all). No significant changes were found in the posterior aberometric parameters. PSF value did not change after CXL (P > 0.05). The corneal topographic measurements not revealed a change in the mean simulated keratometry-1, simulated keratometry-2, and maximum keratometry compared with the baseline measurements (P > 0.05, for all). At 12 months, there was a significant improvement in the uncorrected (UCVA) and best corrected (BCVA) visual acuity (P < 0.001, both). Most corneal aberrations correlated significantly with postoperative BCVA, but changes in HOAs were not statistically associated with improvements in visual acuity. CONCLUSIONS: Transepithelial CXL was effective in stabilizing the keratometric indices and improving the most corneal aberrations in keratoconic eyes 1 year after the procedure. While the healing effect on aberrations after CXL was in total and anterior parameters, no significant changes were observed in the posterior surface. In addition, it was observed that transepithelial CXL treatment did not cause a significant change in PSF distribution data.

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.

Exogenous Collagen Crosslinking is Highly Detrimental to Articular Cartilage Lubrication.

Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear. Here, we examined how the collagen crosslinking agents genipin (GP) and glutaraldehyde (GTA) impact cartilage lubrication using the convergent stationary contact area (cSCA) configuration. Unlike classical configurations, the cSCA sustains biofidelic kinetic friction coefficients (µk) via superposition of interstitial and hydrodynamic pressurization (i.e., tribological rehydration). As expected, glutaraldehyde- and genipin-mediated CXL increased cartilage's tensile and compressive moduli. Although net tribological rehydration was retained after CXL, GP or GTA treatment drastically elevated µk. Both healthy and "OA-like" cartilage (generated via enzymatic digestion) sustained remarkably low µk in saline- (≤0.02) and synovial fluid-lubricated contacts (≤0.006). After CXL, µk increased up to 30-fold, reaching values associated with marked chondrocyte death in vitro. These results demonstrate that mechanical properties (i.e., stiffness) are necessary, but not sufficient, metrics of cartilage function. Furthermore, the marked impairment in lubrication suggests that CXL-mediated stiffening is ill-suited to cartilage preservation or joint resurfacing.

Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS® Registry Analysis.

PURPOSE: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age from 2015 to 2020 and evaluate sociodemographic associations with the treatment approach. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight). METHODS: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression. MAIN OUTCOME MEASURES: Outcomes included percentages and rates of each treatment (collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type. RESULTS: A total of 66 199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05% in 2015 to 29.5% in 2020 (P = 0.008). The average age (standard deviation) of KCN patients decreased from 44.1 (±16.9) years in 2015 to 39.2 (±16.9) years in 2020 (P < 0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age, for example, comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95% confidence interval [CI]) decreased from 0.62 (0.57-0.67; P < 0.0001) for patients aged 21-40 years to 0.03 (0.02-0.04; P < 0.0001) for patients aged > 60 years. Men were more likely than women to have CXL (OR, 1.31; 95% CI, 1.23-1.40; P < 0.0001) and keratoplasty (OR, 1.30; 95% CI, 1.19-1.42; P < 0.0001). Black patients were less likely than White patients to have CXL (OR, 0.70; 95% CI, 0.63-0.77; P < 0.0001) and more likely to have keratoplasty (OR, 2.24; 95% CI, 2.01-2.50; P < 0.0001). Likewise, Hispanic patients had higher odds of CXL (OR, 1.12; 95% CI, 1.00-1.24; P < 0.05) and keratoplasty (OR, 1.29; 95% CI, 1.12-1.50; P < 0.001) compared with non-Hispanic patients. Collagen crosslinking and keratoplasty also varied by region and insurance status. CONCLUSIONS: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, use, or care patterns, and future studies should aim to identify strategies to improve access for all patients. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance.

We have reviewed the development and current status of therapies based on exposure to non-ionizing radiation (with a photon energy less than 10 eV) aimed at suppressing the venous neointimal hyperplasia, and consequentially at avoiding stenosis in arteriovenous grafts. Due to the drawbacks associated with the medical use of ionizing radiation, prominently the radiation-induced cardiovascular disease, the availability of procedures using non-ionizing radiation is becoming a noteworthy objective for the current research. Further, the focus of the review was the use of such procedures for improving the vascular access function and assuring the clinical success of arteriovenous fistulae in hemodialysis patients. Following a brief discussion of the physical principles underlying radiotherapy, the current methods based on non-ionizing radiation, either in use or under development, were described in detail. There are currently five such techniques, including photodynamic therapy (PDT), far-infrared therapy, photochemical tissue passivation (PTP), Alucent vascular scaffolding, and adventitial photocrosslinking. The last three are contingent on the mechanical stiffening achievable by the exogenous photochemical crosslinking of tissular collagen, a process that leads to the decrease of venous compliance. As there are conflicting opinions on the role of compliance mismatch between arterial and venous conduits in a graft, this aspect was also considered in our review.

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.